SBP Pathways Summer 2017

NONPROFIT ORGANIZATION US POSTAGE

PAID

SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

A SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE PUBLICATION | NEUROSCIENCE ISSUE | SUMMER 2017

10901 North Torrey Pines Road La Jolla, California 92037 SBPdiscovery.org

BRAIN Rethinking diseases of the mind

Our work is made possible through the generous donations of people like you.

If you wish to support our research, please email giving@SBPdiscovery.org or call 1-877-454-5702.

NONPROFIT ORGANIZATION US POSTAGE

PAID

SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

A SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE PUBLICATION | NEUROSCIENCE ISSUE | SUMMER 2017

10901 North Torrey Pines Road La Jolla, California 92037 SBPdiscovery.org

BRAIN Rethinking diseases of the mind

Our work is made possible through the generous donations of people like you.

If you wish to support our research, please email giving@SBPdiscovery.org or call 1-877-454-5702.

NEUROSCIENCE ISSUE SUMMER 2017 ON THE COVER Jerold Chun, M.D., Ph.D., recently joined SBP and brought a team of scientists who are looking at the brain one neuron at a time.

See page 4

Contents 4

The Mosaic Brain

8 12

Game On

15

Autism: A Personal Perspective

16 18

The Prebys Center ‘dishes’

19

The SBP-GSK Center for Translational Neuroscience

20

Connecting Individuals to Causes

21 24 25 28

Bringing It for SBP!

30

Science Benefiting Patients

36

Discovery Hub

Rare Bone Disease Sheds Light on Autism

Karen and Stuart Tanz: Getting to the Finish Line Faster

When Gridiron Gives President’s Circle Donors-2016 Breakthroughs in Bipolar Disorder

10901 North Torrey Pines Road La Jolla, California 92037

SBPdiscovery.org

FOLLOW US ON:

@SBPdiscovery

Sanford Burnham Prebys Medical Discovery Institute is a 501(c)3 nonprofit organization.

NEUROSCIENCE ISSUE SUMMER 2017 ON THE COVER Jerold Chun, M.D., Ph.D., recently joined SBP and brought a team of scientists who are looking at the brain one neuron at a time.

See page 4

Contents 4

The Mosaic Brain

8 12

Game On

15

Autism: A Personal Perspective

16 18

The Prebys Center ‘dishes’

19

The SBP-GSK Center for Translational Neuroscience

20

Connecting Individuals to Causes

21 24 25 28

Bringing It for SBP!

30

Science Benefiting Patients

36

Discovery Hub

Rare Bone Disease Sheds Light on Autism

Karen and Stuart Tanz: Getting to the Finish Line Faster

When Gridiron Gives President’s Circle Donors-2016 Breakthroughs in Bipolar Disorder

10901 North Torrey Pines Road La Jolla, California 92037

SBPdiscovery.org

FOLLOW US ON:

@SBPdiscovery

Sanford Burnham Prebys Medical Discovery Institute is a 501(c)3 nonprofit organization.

NEUROSCIENCE ISSUE SUMMER 2017 ON THE COVER Jerold Chun, M.D., Ph.D., recently joined SBP and brought a team of scientists who are looking at the brain one neuron at a time.

See page 4

Contents 4

The Mosaic Brain

8 12

Game On

15

Autism: A Personal Perspective

16 18

The Prebys Center ‘dishes’

19

The SBP-GSK Center for Translational Neuroscience

20

Connecting Individuals to Causes

21 24 25 28

Bringing It for SBP!

30

Science Benefiting Patients

36

Discovery Hub

Rare Bone Disease Sheds Light on Autism

Karen and Stuart Tanz: Getting to the Finish Line Faster

When Gridiron Gives President’s Circle Donors-2016 Breakthroughs in Bipolar Disorder

10901 North Torrey Pines Road La Jolla, California 92037

SBPdiscovery.org

FOLLOW US ON:

@SBPdiscovery

Sanford Burnham Prebys Medical Discovery Institute is a 501(c)3 nonprofit organization.

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LETTER Alzheimer’s disease disrupts the way neurotransmitters travel between synapses.

See page 9.

We Can Make a Difference For many years, my dad would send me a thick manila envelope full of clippings from newspapers and magazines that he thought would be of interest to me. The clippings got increasingly jagged and obscure as his Parkinson’s disease and Lewy Body Dementia progressed. You can imagine the rest of the story—he eventually stopped reading, feeding himself or taking care of basic necessities; he didn’t recognize my mom, his grandchildren or me at the end.

The impact of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is horrific beyond words. Drug discovery and development for these disorders has been met by one failure after another. But scientists have remained undaunted, and several scientific breakthroughs have been reported recently.

I am absolutely convinced that multiple recent discoveries are ripe for translation into meaningful medical advances to address the unmet medical need of patients with neurodegenerative diseases.

Sanford Burnham Prebys Medical Discovery Institute (SBP) is home to several dazzling, innovative neuroscientists who are at the cutting edge of research. Given their know-how in turning insights into new medicines and diagnostics, we can truly make a difference.

But these exciting scientific strides are coming at a time when there are threats to the budget of the National Institutes of Health, which supports much of this research; and there is reticence by biotech and pharma to invest in this area because of past failures.

“We are zeroing in on new disease targets

We increasingly rely on the generosity of individuals such as yourselves to support the research and discoveries that will lead to advances in medicine, which will prevent the indignity and suffering those with neurodegenerative diseases must endure.

and investing in translational research to advance our discoveries to help patients with neurological disorders.”

Perry Nisen, M.D., Ph.D.

Perry Nisen, M.D., Ph.D. Chief Executive Officer Donald Bren Chief Executive Chair

Perry Nisen, M.D., Ph.D.

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LETTER Alzheimer’s disease disrupts the way neurotransmitters travel between synapses.

See page 9.

We Can Make a Difference For many years, my dad would send me a thick manila envelope full of clippings from newspapers and magazines that he thought would be of interest to me. The clippings got increasingly jagged and obscure as his Parkinson’s disease and Lewy Body Dementia progressed. You can imagine the rest of the story—he eventually stopped reading, feeding himself or taking care of basic necessities; he didn’t recognize my mom, his grandchildren or me at the end.

The impact of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is horrific beyond words. Drug discovery and development for these disorders has been met by one failure after another. But scientists have remained undaunted, and several scientific breakthroughs have been reported recently.

I am absolutely convinced that multiple recent discoveries are ripe for translation into meaningful medical advances to address the unmet medical need of patients with neurodegenerative diseases.

Sanford Burnham Prebys Medical Discovery Institute (SBP) is home to several dazzling, innovative neuroscientists who are at the cutting edge of research. Given their know-how in turning insights into new medicines and diagnostics, we can truly make a difference.

But these exciting scientific strides are coming at a time when there are threats to the budget of the National Institutes of Health, which supports much of this research; and there is reticence by biotech and pharma to invest in this area because of past failures.

“We are zeroing in on new disease targets

We increasingly rely on the generosity of individuals such as yourselves to support the research and discoveries that will lead to advances in medicine, which will prevent the indignity and suffering those with neurodegenerative diseases must endure.

and investing in translational research to advance our discoveries to help patients with neurological disorders.”

Perry Nisen, M.D., Ph.D.

Perry Nisen, M.D., Ph.D. Chief Executive Officer Donald Bren Chief Executive Chair

Perry Nisen, M.D., Ph.D.

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The Mosaic Brain Dr. Jerold Chun is getting to the bottom of Alzheimer’s disease one neuron at time The human brain is an enormously intricate mosaic. With mosaics, you have to assemble the pieces one at a time to see the big picture,” says Jerold Chun, M.D., Ph.D., professor and senior vice president of Sanford Burnham Prebys (SBP) Neuroscience Drug Discovery Program. “By understanding these brain pieces—single neurons—we will see the bigger picture of the brain, its diseases and how to treat them.”

Chun, a pioneer in neuroscience, recently joined our Institute, bringing his 25-member research team with him from The Scripps Research Institute.

The diligent and bright young students and postdocs specialize in genomic mosaicism, the DNA differences among cells of our brain and body.

“People used to think that each cell in the body had the exact same genetic makeup—23 pairs of chromosomes, identical copies of genes and DNA sequences,” Chun explains. “But with modern technology to analyze singlecell genomes, we now realize that cells from the same person can actually have different genomes, creating a genomic mosaic.”

Chun’s lab was the first to show that cells with altered DNA content that includes more or less than two copies of each chromosome—aneuploid cells—are found in the brain. Before then, DNA was thought to be identical in every brain cell.

“In the brain, each neuron is unique, which contributes to the overall picture of how this remarkable organ controls our thoughts and all of our body’s functions,” says Chun.

Jerold Chun, M.D., Ph.D., is professor and senior vice president of the Neuroscience Drug Discovery Program.

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The Mosaic Brain Dr. Jerold Chun is getting to the bottom of Alzheimer’s disease one neuron at time The human brain is an enormously intricate mosaic. With mosaics, you have to assemble the pieces one at a time to see the big picture,” says Jerold Chun, M.D., Ph.D., professor and senior vice president of Sanford Burnham Prebys (SBP) Neuroscience Drug Discovery Program. “By understanding these brain pieces—single neurons—we will see the bigger picture of the brain, its diseases and how to treat them.”

Chun, a pioneer in neuroscience, recently joined our Institute, bringing his 25-member research team with him from The Scripps Research Institute.

The diligent and bright young students and postdocs specialize in genomic mosaicism, the DNA differences among cells of our brain and body.

“People used to think that each cell in the body had the exact same genetic makeup—23 pairs of chromosomes, identical copies of genes and DNA sequences,” Chun explains. “But with modern technology to analyze singlecell genomes, we now realize that cells from the same person can actually have different genomes, creating a genomic mosaic.”

Chun’s lab was the first to show that cells with altered DNA content that includes more or less than two copies of each chromosome—aneuploid cells—are found in the brain. Before then, DNA was thought to be identical in every brain cell.

“In the brain, each neuron is unique, which contributes to the overall picture of how this remarkable organ controls our thoughts and all of our body’s functions,” says Chun.

Jerold Chun, M.D., Ph.D., is professor and senior vice president of the Neuroscience Drug Discovery Program.

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“It’s worth noting that DNA variation in the brain is not all bad. It may also account for why human behavior can vary so widely, from genius to madness.”

Jerold Chun, M.D., Ph.D.

SUMMER 2017

CREATING THE MOSAIC “Genomic mosaicism actually starts before birth,” Chun explains. “When a brain is forming in the womb, cells develop, divide and copy chromosomes rapidly. Each cell should have an identical set of chromosomes, packaging thousands of genes. But sometimes chromosomes aren’t evenly distributed or completely copied when cells divide, causing aneuploidy, as well as other genomic changes.”

His team was also the first to show that the brains of Alzheimer’s patients have altered genomic mosaicism compared to brains without the disease. Alzheimer’s neurons can further have more copies of a disease-causing gene called amyloid precursor protein (APP). APP is the starting point of amyloid plaques, hard clumps of protein that disrupt brain cell communications and a prominent feature of Alzheimer’s disease. Drugs that eliminate or prevent amyloid plaques are a major focus of current experimental treatments.

GENETICS OF ALZEIMER’S DISEASE “Less than 1 percent of all cases of Alzheimer’s disease are ‘familial’—or inherited,” explains Chun. Most cases are described as “sporadic,” which means that there is not a specific family link, but a complex combination of things that include our environment, lifestyle, genes and genomic mosaicism.

“It turns out that for almost all neuropsychiatric diseases out there, the most common form is sporadic, so we think our research approach will apply to other diseases as well.”

THE CHALLENGE DNA changes in the brain can’t be detected by swabbing cells from the inside of your mouth, or taking a blood sample. According to Chun, “The only way we can really get to the bottom of the disease is by understanding the brain itself, down to the level of single neurons. My lab’s goal is to pursue and translate this fundamental research into actual therapeutics for Alzheimer’s, as well as other brain diseases.”

MOVING TO SBP Translational neuroscience is what brought Chun to SBP. “New therapies are desperately needed for patients with brain disorders,” says Chun. “Today patients can only receive treatment for their symptoms without really impacting disease.”

that has subsequently enabled the development of novel drugs including fingolimod (Gilenya®), the first oral drug to treat multiple sclerosis. His team’s LP research also has relevance to other neurological disorders such as stroke and hydrocephalus.

In conversations with SBP’s CEO, Perry Nisen, M.D., Ph.D., Chun says they “both felt an urgency to move—or translate— basic lab discoveries into new medicines.

We share a passion for finding new drugs that prevent, slow and perhaps even one day cure challenging and medically important diseases like Alzheimer’s.

“The path to new brain drugs is not an easy one,” says Chun. “Some steps take us forward, and some don’t. But even perceived setbacks add to our understanding of what we need to do to make an effective drug. The process is really more of a marathon than a sprint.”

“Working with the Conrad Prebys Center for Chemical Genomics at SBP—one of the most sophisticated drug discovery facilities in academia—gives my lab a better chance to turn our scientific discoveries into effective therapeutics,” says Chun.

TRACK RECORD OF SUCCESS Chun is no stranger to finding paths to new drugs. His lab identified the first lysophospholipid (LP) receptor, leading to an entire field of study

Chun knows something about marathons, having completed his 44th consecutive Honolulu Marathon last year, as well as an earlier Boston Marathon. Born in Philadelphia and raised in Hawaii, he attended Stanford University, where he completed his M.D./Ph.D. in neurosciences followed by postdoctoral studies at MIT. Since then, he has held both academic professorships and management positions in industry.

And now his journey continues at SBP.

ALZHEIMER’S DISEASE

As the disease progresses, the branched projections of a neuron, called “dendrites,” degenerate and cause neurons to atrophy. When neurons are no longer able to function, patients suffer increased memory loss and personality changes.

NORMAL AND ALZHEIMER’S BRAINS PET SCANS

A PET scan (a form of 3-D imaging) reveals regions of the brain showing darkened areas representative of the lack of neural activity.

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“It’s worth noting that DNA variation in the brain is not all bad. It may also account for why human behavior can vary so widely, from genius to madness.”

Jerold Chun, M.D., Ph.D.

SUMMER 2017

CREATING THE MOSAIC “Genomic mosaicism actually starts before birth,” Chun explains. “When a brain is forming in the womb, cells develop, divide and copy chromosomes rapidly. Each cell should have an identical set of chromosomes, packaging thousands of genes. But sometimes chromosomes aren’t evenly distributed or completely copied when cells divide, causing aneuploidy, as well as other genomic changes.”

His team was also the first to show that the brains of Alzheimer’s patients have altered genomic mosaicism compared to brains without the disease. Alzheimer’s neurons can further have more copies of a disease-causing gene called amyloid precursor protein (APP). APP is the starting point of amyloid plaques, hard clumps of protein that disrupt brain cell communications and a prominent feature of Alzheimer’s disease. Drugs that eliminate or prevent amyloid plaques are a major focus of current experimental treatments.

GENETICS OF ALZEIMER’S DISEASE “Less than 1 percent of all cases of Alzheimer’s disease are ‘familial’—or inherited,” explains Chun. Most cases are described as “sporadic,” which means that there is not a specific family link, but a complex combination of things that include our environment, lifestyle, genes and genomic mosaicism.

“It turns out that for almost all neuropsychiatric diseases out there, the most common form is sporadic, so we think our research approach will apply to other diseases as well.”

THE CHALLENGE DNA changes in the brain can’t be detected by swabbing cells from the inside of your mouth, or taking a blood sample. According to Chun, “The only way we can really get to the bottom of the disease is by understanding the brain itself, down to the level of single neurons. My lab’s goal is to pursue and translate this fundamental research into actual therapeutics for Alzheimer’s, as well as other brain diseases.”

MOVING TO SBP Translational neuroscience is what brought Chun to SBP. “New therapies are desperately needed for patients with brain disorders,” says Chun. “Today patients can only receive treatment for their symptoms without really impacting disease.”

that has subsequently enabled the development of novel drugs including fingolimod (Gilenya®), the first oral drug to treat multiple sclerosis. His team’s LP research also has relevance to other neurological disorders such as stroke and hydrocephalus.

In conversations with SBP’s CEO, Perry Nisen, M.D., Ph.D., Chun says they “both felt an urgency to move—or translate— basic lab discoveries into new medicines.

We share a passion for finding new drugs that prevent, slow and perhaps even one day cure challenging and medically important diseases like Alzheimer’s.

“The path to new brain drugs is not an easy one,” says Chun. “Some steps take us forward, and some don’t. But even perceived setbacks add to our understanding of what we need to do to make an effective drug. The process is really more of a marathon than a sprint.”

“Working with the Conrad Prebys Center for Chemical Genomics at SBP—one of the most sophisticated drug discovery facilities in academia—gives my lab a better chance to turn our scientific discoveries into effective therapeutics,” says Chun.

TRACK RECORD OF SUCCESS Chun is no stranger to finding paths to new drugs. His lab identified the first lysophospholipid (LP) receptor, leading to an entire field of study

Chun knows something about marathons, having completed his 44th consecutive Honolulu Marathon last year, as well as an earlier Boston Marathon. Born in Philadelphia and raised in Hawaii, he attended Stanford University, where he completed his M.D./Ph.D. in neurosciences followed by postdoctoral studies at MIT. Since then, he has held both academic professorships and management positions in industry.

And now his journey continues at SBP.

ALZHEIMER’S DISEASE

As the disease progresses, the branched projections of a neuron, called “dendrites,” degenerate and cause neurons to atrophy. When neurons are no longer able to function, patients suffer increased memory loss and personality changes.

NORMAL AND ALZHEIMER’S BRAINS PET SCANS

A PET scan (a form of 3-D imaging) reveals regions of the brain showing darkened areas representative of the lack of neural activity.

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Huaxi Xu, Ph.D., professor and director of SBP’s Neuroscience Initiative

Game On

Dr. Huaxi Xu takes on the challenge of advancing research on the plaques and tangles of dementia On rare occasions, Huaxi Xu, Ph.D., takes a short break from leading a team of researchers investigating how neurodegenerative diseases, such as Alzheimer’s, develop. When he does, it’s usually a quick game of pingpong in the nearby lunchroom with a lab member. But even then his mind is not far from his work.

“In the brain, neurons shoot signals to each other, similar to how pingpong players lob volleys back and forth. However, when diseases like Alzheimer’s develop, the volley is interrupted by obstacles that block the brain’s neurotransmitters necessary for learning and memory,” explains Xu. “Unfortunately, with Alzheimer’s you can’t start a new game—the condition is chronic and irreversible.”

Xu, the Jeanne and Gary Herberger Leadership Chair in Neuroscience, and director of our Neuroscience Initiative, is researching the early biological events going on inside and between neurons that lead to neurodegeneration. He believes that it’s fundamentally important to find ways to diagnose and treat these patients early, before the damage starts.

“If you lose a neuron, we can’t replace it, unlike skin cells which can grow and be replaced,” says Xu. “The more we understand about the beginnings of the degenerative process, the better equipped we are to find drugs to slow down, or even prevent, dementia.

THE INSIDE STORY Inside healthy neurons, a protein called “tau” (as in the Greek letter for “t”) keeps the structural order that cells need for transferring molecules. When neurodegenerative diseases claw their way into the brain, tau proteins become twisted and tangled—interfering with brain signaling.

“Tau tangles are a prime suspect in Alzheimer’s. They are a pathological hallmark of the disease—which means they are invariably present in the brains of patients,” says Xu. “There is actually a whole class of neurodegenerative diseases called ‘taupathies’ that are signified by tau tangles, so preventing the formation of tangles may extend to other types of dementia,” he adds. “We are looking at the abnormal phosphorylation of tau, which is an early step in the process. Drugs that inhibit phosphorylation may provide clinical benefits by halting the accumulation of tau tangles.”

THE OUTSIDE STORY To add to the complexity of Alzheimer’s disease, another set of proteins called amyloid beta can form amyloid plaques, or clumps, outside the neurons. If you can picture how mounds of thick clumps forming on a pingpong table would ruin the game, you can envision how amyloid clumps affect how neurons communicate.

“Amyolid plaques are also a pathological hallmark of Alzheimer’s,” Xu says. “And we still don’t have a clear picture of why and how they form in the brain or their exact connection to the disease.

“Our understanding of how dementia develops is far behind our understanding of how cancer develops. In contrast to cancer, there are no surgeries, cures or effective drugs to treat Alzheimer’s,” Xu adds.

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Huaxi Xu, Ph.D., professor and director of SBP’s Neuroscience Initiative

Game On

Dr. Huaxi Xu takes on the challenge of advancing research on the plaques and tangles of dementia On rare occasions, Huaxi Xu, Ph.D., takes a short break from leading a team of researchers investigating how neurodegenerative diseases, such as Alzheimer’s, develop. When he does, it’s usually a quick game of pingpong in the nearby lunchroom with a lab member. But even then his mind is not far from his work.

“In the brain, neurons shoot signals to each other, similar to how pingpong players lob volleys back and forth. However, when diseases like Alzheimer’s develop, the volley is interrupted by obstacles that block the brain’s neurotransmitters necessary for learning and memory,” explains Xu. “Unfortunately, with Alzheimer’s you can’t start a new game—the condition is chronic and irreversible.”

Xu, the Jeanne and Gary Herberger Leadership Chair in Neuroscience, and director of our Neuroscience Initiative, is researching the early biological events going on inside and between neurons that lead to neurodegeneration. He believes that it’s fundamentally important to find ways to diagnose and treat these patients early, before the damage starts.

“If you lose a neuron, we can’t replace it, unlike skin cells which can grow and be replaced,” says Xu. “The more we understand about the beginnings of the degenerative process, the better equipped we are to find drugs to slow down, or even prevent, dementia.

THE INSIDE STORY Inside healthy neurons, a protein called “tau” (as in the Greek letter for “t”) keeps the structural order that cells need for transferring molecules. When neurodegenerative diseases claw their way into the brain, tau proteins become twisted and tangled—interfering with brain signaling.

“Tau tangles are a prime suspect in Alzheimer’s. They are a pathological hallmark of the disease—which means they are invariably present in the brains of patients,” says Xu. “There is actually a whole class of neurodegenerative diseases called ‘taupathies’ that are signified by tau tangles, so preventing the formation of tangles may extend to other types of dementia,” he adds. “We are looking at the abnormal phosphorylation of tau, which is an early step in the process. Drugs that inhibit phosphorylation may provide clinical benefits by halting the accumulation of tau tangles.”

THE OUTSIDE STORY To add to the complexity of Alzheimer’s disease, another set of proteins called amyloid beta can form amyloid plaques, or clumps, outside the neurons. If you can picture how mounds of thick clumps forming on a pingpong table would ruin the game, you can envision how amyloid clumps affect how neurons communicate.

“Amyolid plaques are also a pathological hallmark of Alzheimer’s,” Xu says. “And we still don’t have a clear picture of why and how they form in the brain or their exact connection to the disease.

“Our understanding of how dementia develops is far behind our understanding of how cancer develops. In contrast to cancer, there are no surgeries, cures or effective drugs to treat Alzheimer’s,” Xu adds.

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“We are developing game-changing methods to discover therapies to improve the lives of Alzheimer’s patients.”

Huaxi Xu, Ph.D.

FACTS ABOUT ALZHEIMER’S Alzheimer’s disease is the 6TH leading cause of death in the U.S. Every 66 SECONDS, someone in the U.S. will develop Alzheimer’s disease

1 IN 10 PEOPLE age 65 and older has Alzheimer’s disease

Source: Alzheimer’s Association

A CLUE FROM DOWN SYNDROME Interestingly, Down syndrome gives us a clue to how Alzheimer’s disease develops. As medical care has improved, those with Down syndrome are living longer lives than ever before—but the majority become victims of early-onset Alzheimer’s disease.

Xu is researching how Alzheimer’s disease is linked to Down syndrome. By working on the genes that can decrease amyloid plaques, Xu is hoping to find drugs to “clear the playing field,” so to speak, so neurotransmitters can bounce through the brain uninhibited by plaques.

People with Down syndrome are born with an extra copy of chromosome 21, which carries a specific gene called the amyloid precursor protein (APP). When there is an abundance of the APP protein, it can cause amyloid clumps in the brain.

His contributions have laid the groundwork for neurodegenerative drug-targeting strategies; and have had a broad influence on the field, particularly in understanding how Alzheimer’s disease can be diagnosed early, before there is too much permanent neural damage in the brain.

By the age of 40, most individuals with Down syndrome already exhibit amyloid clumps in the brain, an indication of Alzheimer’s disease.

By the age of 65, more than 75 percent of people with Down syndrome have Alzheimer’s disease. According to the Alzheimer’s Association, that figure is six times higher than the age group of people who don’t have Down syndrome.

Light micrograph of human brain tissue from Alzheimer’s disease patient stained for amyloid protein. A dark-staining plaque is visible in the center.

“I wish to integrate the strengths, collaborative spirit and wide-ranging technological capabilities at our Institute to evolve our capacity to bring knowledge from the lab bench to finding a cure. In doing so, we will gain significant ground toward a treatment for Alzheimer’s disease and other age-related neurological disorders.”

Huaxi Xu, Ph.D., (center) leads a team of scientists exploring the causes of dementia.

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“We are developing game-changing methods to discover therapies to improve the lives of Alzheimer’s patients.”

Huaxi Xu, Ph.D.

FACTS ABOUT ALZHEIMER’S Alzheimer’s disease is the 6TH leading cause of death in the U.S. Every 66 SECONDS, someone in the U.S. will develop Alzheimer’s disease

1 IN 10 PEOPLE age 65 and older has Alzheimer’s disease

Source: Alzheimer’s Association

A CLUE FROM DOWN SYNDROME Interestingly, Down syndrome gives us a clue to how Alzheimer’s disease develops. As medical care has improved, those with Down syndrome are living longer lives than ever before—but the majority become victims of early-onset Alzheimer’s disease.

Xu is researching how Alzheimer’s disease is linked to Down syndrome. By working on the genes that can decrease amyloid plaques, Xu is hoping to find drugs to “clear the playing field,” so to speak, so neurotransmitters can bounce through the brain uninhibited by plaques.

People with Down syndrome are born with an extra copy of chromosome 21, which carries a specific gene called the amyloid precursor protein (APP). When there is an abundance of the APP protein, it can cause amyloid clumps in the brain.

His contributions have laid the groundwork for neurodegenerative drug-targeting strategies; and have had a broad influence on the field, particularly in understanding how Alzheimer’s disease can be diagnosed early, before there is too much permanent neural damage in the brain.

By the age of 40, most individuals with Down syndrome already exhibit amyloid clumps in the brain, an indication of Alzheimer’s disease.

By the age of 65, more than 75 percent of people with Down syndrome have Alzheimer’s disease. According to the Alzheimer’s Association, that figure is six times higher than the age group of people who don’t have Down syndrome.

Light micrograph of human brain tissue from Alzheimer’s disease patient stained for amyloid protein. A dark-staining plaque is visible in the center.

“I wish to integrate the strengths, collaborative spirit and wide-ranging technological capabilities at our Institute to evolve our capacity to bring knowledge from the lab bench to finding a cure. In doing so, we will gain significant ground toward a treatment for Alzheimer’s disease and other age-related neurological disorders.”

Huaxi Xu, Ph.D., (center) leads a team of scientists exploring the causes of dementia.

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Rare Bone Disease Sheds Light on Autism Dr. Yamaguchi’s 30-year career at SBP has led him to autism research

Yu Yamaguchi, M.D., Ph.D., is a professor in the Human Genetics Program.

Yu Yamaguchi, M.D., Ph.D., was in the midst of another 14-hour-day in the lab when his phone rang. A woman named Sarah Ziegler explained that her son had a rare disease called multiple hereditary exostoses (MHE). Sarah was active in helping a patient support group for MHE. She noticed that children with MHE often exhibit autistic behaviors—something other parents of MHE children had described to her.

MHE is an incurable genetic condition that results in multiple bone growths that are painful and often disfiguring. The disease, mostly diagnosed in children before the age of 12, is caused by a mutation in one of two genes, EXT1 or EXT2, which are necessary to produce heparan sulfate—a long sugar chain that helps bone cells grow and thrive.

Yamaguchi had been studying heparan sulfate—not in bones, but in nerve cells and the brain. At Sarah’s prodding, Yamaguchi turned to looking at the connections between MHE and autism.

It wouldn’t be the first time he’d turned his attention to a new direction. Both his mother and father were physicians, and two grandparents were physicians. So it seemed only natural that he graduated from Tohuku University in Sendai, Japan, with a medical degree. But the standard career path that stretched ahead in his homeland didn’t excite him. “I wanted to do postdoctoral work in the United States,” he says, “to decide what area of medicine I wanted to pursue.”

“Although being a glycobiologist may not sound like the most exciting job in the world, it has provided me with unique opportunities to connect with patients and families who are seeking better treatments and cures.”

Yu Yamaguchi, M.D., Ph.D.

THE BEGINNING Yamaguchi wrote to several prominent scientists, including Erkki Ruoslahti, M.D., Ph.D., former scientific director, president and CEO, and now distinguished professor at Sanford Burnham Prebys Medical Research Institute (SBP). Ruoslahti replied, inviting the gifted student to join his lab. There, Yamaguchi started his career in glycobiology—the study of how sugar molecules attach to proteins on cells to influence biological processes.

Now, 30 some years later and a professor in the Human Genetics Program, Yamaguchi’s work has revealed a clear relationship between heparan sulfate deficiencies in the brain and behaviors consistent with autism.

“When I first spoke with Sarah,” recalls Yamaguchi, “I was focusing my studies on how heparan sulfate was concentrated in the synapses, or communication junctions, between nerve cells in the brain. I suspected that heparin sulfate was somehow implicated as a modifier of autism candidate genes, but I hadn’t proven that.”

Sarah urged him to explore a link with the EXT1 gene. She was certain that what she and other parents were noticing in their children—poor communication skills, repetitive behaviors and avoidance of social interaction—were the symptoms described for autism spectrum disorder.

“No textbook had made this connection between a bone disease and a neurological disease,” Yamaguchi said, “but I was curious.”

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Rare Bone Disease Sheds Light on Autism Dr. Yamaguchi’s 30-year career at SBP has led him to autism research

Yu Yamaguchi, M.D., Ph.D., is a professor in the Human Genetics Program.

Yu Yamaguchi, M.D., Ph.D., was in the midst of another 14-hour-day in the lab when his phone rang. A woman named Sarah Ziegler explained that her son had a rare disease called multiple hereditary exostoses (MHE). Sarah was active in helping a patient support group for MHE. She noticed that children with MHE often exhibit autistic behaviors—something other parents of MHE children had described to her.

MHE is an incurable genetic condition that results in multiple bone growths that are painful and often disfiguring. The disease, mostly diagnosed in children before the age of 12, is caused by a mutation in one of two genes, EXT1 or EXT2, which are necessary to produce heparan sulfate—a long sugar chain that helps bone cells grow and thrive.

Yamaguchi had been studying heparan sulfate—not in bones, but in nerve cells and the brain. At Sarah’s prodding, Yamaguchi turned to looking at the connections between MHE and autism.

It wouldn’t be the first time he’d turned his attention to a new direction. Both his mother and father were physicians, and two grandparents were physicians. So it seemed only natural that he graduated from Tohuku University in Sendai, Japan, with a medical degree. But the standard career path that stretched ahead in his homeland didn’t excite him. “I wanted to do postdoctoral work in the United States,” he says, “to decide what area of medicine I wanted to pursue.”

“Although being a glycobiologist may not sound like the most exciting job in the world, it has provided me with unique opportunities to connect with patients and families who are seeking better treatments and cures.”

Yu Yamaguchi, M.D., Ph.D.

THE BEGINNING Yamaguchi wrote to several prominent scientists, including Erkki Ruoslahti, M.D., Ph.D., former scientific director, president and CEO, and now distinguished professor at Sanford Burnham Prebys Medical Research Institute (SBP). Ruoslahti replied, inviting the gifted student to join his lab. There, Yamaguchi started his career in glycobiology—the study of how sugar molecules attach to proteins on cells to influence biological processes.

Now, 30 some years later and a professor in the Human Genetics Program, Yamaguchi’s work has revealed a clear relationship between heparan sulfate deficiencies in the brain and behaviors consistent with autism.

“When I first spoke with Sarah,” recalls Yamaguchi, “I was focusing my studies on how heparan sulfate was concentrated in the synapses, or communication junctions, between nerve cells in the brain. I suspected that heparin sulfate was somehow implicated as a modifier of autism candidate genes, but I hadn’t proven that.”

Sarah urged him to explore a link with the EXT1 gene. She was certain that what she and other parents were noticing in their children—poor communication skills, repetitive behaviors and avoidance of social interaction—were the symptoms described for autism spectrum disorder.

“No textbook had made this connection between a bone disease and a neurological disease,” Yamaguchi said, “but I was curious.”

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PATHWAYS

FACTS ABOUT AUTISM 1 IN 68 children is affected by autism Boys are FOUR TIMES more likely to have autism than girls About 40% of children with autism do not speak Autism is the FASTEST-GROWING developmental disorder

Source: National Autism Association

SUMMER 2017

CONNECTING TO AUTISM Soon thereafter, Fumitoshi Irie, Ph.D., a research assistant professor in Yamaguchi’s lab, was leading a project to create a mouse model with a mutated EXT1 gene in just a certain type of neuron in the brain to connect heparan sulfate deficiencies with social issues.

The mice proved that Sarah and the other parents were right. As they matured, these mice avoided interacting with other mice and exhibited uncharacteristic repetitive behaviors. Yamaguchi and his team published their findings in Proceedings of the National Academy of Science (PNAS), linking the EXT1 mutation and heparan sulfate deficiency with autism in 2012, a major step toward understanding this complex disease. His valuable mouse model has been distributed

to nearly 50 labs around the world that are studying not only bones but also the nervous system.

Today, Irie and other researchers in Yamaguchi’s lab are analyzing DNA samples from individuals with autism to look for mutations in additional genes, like EXT1, involved in heparan sulfate synthesis. They hope to reveal networks of molecules that contribute to autism and other childhood mental disorders.

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FACULTY

Autism: A Personal Perspective

“While not all children with autism have MHE, or vice versa, there is evidence that some people with autism have deficiencies in heparan sulftate,” Yamaguchi says.

“Our research goal is to find new disease targets that will let us screen for drugs that could boost levels of heparan sulfate and potentially improve the lives of these children who need special care.”

Fumitoshi Irie, Ph.D., a research assistant professor in Yu Yamaguchi’s lab, spends his days studying the brains of mice engineered to display autistic behaviors. Later, at home, he turns to the job of helping his autistic son with the daily routines most of us take for granted. The poignant connection between work and family drives him to continue seeking the cause—or causes— of this complex brain disorder.

Irie and his wife have two autistic children. Although their daughter is high functioning and well-integrated into society, their 19-year old son, Koji, has a more severe version of the spectrum disorder. To provide the personal support and attention he requires, the parents have coordinated their schedules.

Fumitoshi Irie, Ph.D., and Yu Yamaguchi, Ph.D.

“My wife is mainly in charge of school and hospital issues,” Irie says. “I usually come to work early so that I can leave early and take Koji to therapies such as sports, music and behavior classes. We work as a team and regularly consult with professionals for direction on tailoring programs to meet Koji’s needs.”

At SBP, Irie relentlessly pursues a line of investigation that may one day help his son and others like him. “I had spent about 10 years studying a disease called multiple hereditary exostoses (MHE) and how neuron synapses form in the brain, but when we discovered a molecular link between MHE and autism, I eagerly shifted to autism research,” he says.

Irie finds the potential in his studies stimulating. “It’s a difficult disorder,” he admits. “Symptoms can vary dramatically in patients, but therapy and services can really help kids and their parents.”

Fumitoshi Irie, Ph.D. (right), and his son, Koji (left) at Petco Park

“I hope our research will lead to discoveries that improve the understanding, diagnosis and treatment of autism spectrum disorders.”

Fumitoshi Irie, Ph.D.

14

PATHWAYS

FACTS ABOUT AUTISM 1 IN 68 children is affected by autism Boys are FOUR TIMES more likely to have autism than girls About 40% of children with autism do not speak Autism is the FASTEST-GROWING developmental disorder

Source: National Autism Association

SUMMER 2017

CONNECTING TO AUTISM Soon thereafter, Fumitoshi Irie, Ph.D., a research assistant professor in Yamaguchi’s lab, was leading a project to create a mouse model with a mutated EXT1 gene in just a certain type of neuron in the brain to connect heparan sulfate deficiencies with social issues.

The mice proved that Sarah and the other parents were right. As they matured, these mice avoided interacting with other mice and exhibited uncharacteristic repetitive behaviors. Yamaguchi and his team published their findings in Proceedings of the National Academy of Science (PNAS), linking the EXT1 mutation and heparan sulfate deficiency with autism in 2012, a major step toward understanding this complex disease. His valuable mouse model has been distributed

to nearly 50 labs around the world that are studying not only bones but also the nervous system.

Today, Irie and other researchers in Yamaguchi’s lab are analyzing DNA samples from individuals with autism to look for mutations in additional genes, like EXT1, involved in heparan sulfate synthesis. They hope to reveal networks of molecules that contribute to autism and other childhood mental disorders.

15

FACULTY

Autism: A Personal Perspective

“While not all children with autism have MHE, or vice versa, there is evidence that some people with autism have deficiencies in heparan sulftate,” Yamaguchi says.

“Our research goal is to find new disease targets that will let us screen for drugs that could boost levels of heparan sulfate and potentially improve the lives of these children who need special care.”

Fumitoshi Irie, Ph.D., a research assistant professor in Yu Yamaguchi’s lab, spends his days studying the brains of mice engineered to display autistic behaviors. Later, at home, he turns to the job of helping his autistic son with the daily routines most of us take for granted. The poignant connection between work and family drives him to continue seeking the cause—or causes— of this complex brain disorder.

Irie and his wife have two autistic children. Although their daughter is high functioning and well-integrated into society, their 19-year old son, Koji, has a more severe version of the spectrum disorder. To provide the personal support and attention he requires, the parents have coordinated their schedules.

Fumitoshi Irie, Ph.D., and Yu Yamaguchi, Ph.D.

“My wife is mainly in charge of school and hospital issues,” Irie says. “I usually come to work early so that I can leave early and take Koji to therapies such as sports, music and behavior classes. We work as a team and regularly consult with professionals for direction on tailoring programs to meet Koji’s needs.”

At SBP, Irie relentlessly pursues a line of investigation that may one day help his son and others like him. “I had spent about 10 years studying a disease called multiple hereditary exostoses (MHE) and how neuron synapses form in the brain, but when we discovered a molecular link between MHE and autism, I eagerly shifted to autism research,” he says.

Irie finds the potential in his studies stimulating. “It’s a difficult disorder,” he admits. “Symptoms can vary dramatically in patients, but therapy and services can really help kids and their parents.”

Fumitoshi Irie, Ph.D. (right), and his son, Koji (left) at Petco Park

“I hope our research will lead to discoveries that improve the understanding, diagnosis and treatment of autism spectrum disorders.”

Fumitoshi Irie, Ph.D.

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PATHWAYS

SUMMER 2017

DRUG DISCOVERY

The Prebys Center

‘dishes’

It’s a brave new world where patient skin cells may soon lead to therapeutics for hard-to-treat neurological disorders

Can creating a “disease in a dish” help treat neurological disorders? Researchers at SBP’s Conrad Prebys Center for Chemical Genomics (Prebys Center) think so.

Using the latest stem cell technology, researchers take skin cells from patients diagnosed with Alzheimer’s, bipolar disorder or schizophrenia, reprogram those cells in a culture dish to an induced pluripotent stem cell, then coax the stem cells to grow into brain cells, e.g., neurons. Neurons generated this way have the same genetic material as the patient. Scientists hope that by observing these neurons, they can determine what’s going on—and wrong—in these hard-to-treat neurological disorders.

“It’s sort of ‘brave new world,’ with tremendous potential to shed light on the disease process at the cell level,” says Michael Jackson, Ph.D., senior vice president of Drug Discovery and Development at Sanford Burnham Prebys Medical Discovery Institute’s (SBP’s) Prebys Center.

“In Alzheimer’s disease, for example, there are no drugs to stop the progression of the disease despite huge efforts in the past 20 years by researchers in both academia and industry,” adds Jackson. “We are hopeful that our ‘disease in a dish’ approach will change that.”

Prior to stem cell technology, researchers relied on animal models—mice bred to develop symptoms of Alzheimer’s—to study the disease. “Since a mouse lives an average of two years, and humans an average of 80 years, one questions the reliability of using mice exhibiting Alzheimer’s symptoms to find drugs that will work in humans,” explains Jackson. “Biologically there are big differences.”

Anne Bang, Ph.D., director of cell biology at the Prebys Center, agrees. “A drug that works in mice sometimes doesn’t work in humans. Being able to grow human neurons in a dish provides a completely new approach to modeling neurological disease and searching for drugs, which actually takes into account the complexity of human genetics contributing to disease severity and risk.”

RISKS WORTH TAKING The Prebys Center is known for taking on innovative, high-risk projects that most drug discovery companies won’t pursue. These are the projects that may lead to important breakthroughs and innovative therapeutics. For

their current investigations into neurological disorders, Jackson and Bang have found equally ambitious partners.

an unprecedented opportunity for advancing our knowledge about these difficult-to-treat neurological conditions.

Jackson’s team is partnering with the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto to find potential treatments for Alzheimer’s, Parkinson’s and other neurodegenerative conditions.

“Many people question if the biological processes we are targeting can even be affected with a drug,” he says. “But we believe in taking risks and using technology to push the boundaries to find drugs that could make the risks worth taking. We won’t know if it’s possible unless we try.”

“The industrial-scale capabilities of the Prebys Center really support the team’s investigations. Having the sort of high-throughput automation that we have here—for validation, reproducibility and drug target discovery—is invaluable,” Bang explains.

Bang is using the “disease in a dish” strategy to unravel the mechanisms behind two other complex neurological conditions, bipolar disorder and schizophrenia.

She is collaborating with partners across the nation under a five-year, $15.4 million grant from the National Institutes of Health (NIH) that teams SBP with Johns Hopkins, the Salk Institute, the University of Michigan and two industry partners, Janssen Research & Development and Cellular Dynamics International.

“Being able to grow various types of patient-specific, disease-relevant human neurons that can be studied under controlled conditions offers

IT TAKES PASSION It can take years from growing a neuron to developing a prototype drug—so what keeps researchers inspired? “Actually, it’s fascinating work,” Bang says. “I’m addicted to getting answers to my questions.”

Adds Jackson, “These risky projects either appeal to you or they don’t.

But to achieve success you have to explore lots of different avenues— you develop a drug-hunter mentality, accept the risk and stay motivated by keeping patient needs firmly in focus at all times.

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PATHWAYS

SUMMER 2017

DRUG DISCOVERY

The Prebys Center

‘dishes’

It’s a brave new world where patient skin cells may soon lead to therapeutics for hard-to-treat neurological disorders

Can creating a “disease in a dish” help treat neurological disorders? Researchers at SBP’s Conrad Prebys Center for Chemical Genomics (Prebys Center) think so.

Using the latest stem cell technology, researchers take skin cells from patients diagnosed with Alzheimer’s, bipolar disorder or schizophrenia, reprogram those cells in a culture dish to an induced pluripotent stem cell, then coax the stem cells to grow into brain cells, e.g., neurons. Neurons generated this way have the same genetic material as the patient. Scientists hope that by observing these neurons, they can determine what’s going on—and wrong—in these hard-to-treat neurological disorders.

“It’s sort of ‘brave new world,’ with tremendous potential to shed light on the disease process at the cell level,” says Michael Jackson, Ph.D., senior vice president of Drug Discovery and Development at Sanford Burnham Prebys Medical Discovery Institute’s (SBP’s) Prebys Center.

“In Alzheimer’s disease, for example, there are no drugs to stop the progression of the disease despite huge efforts in the past 20 years by researchers in both academia and industry,” adds Jackson. “We are hopeful that our ‘disease in a dish’ approach will change that.”

Prior to stem cell technology, researchers relied on animal models—mice bred to develop symptoms of Alzheimer’s—to study the disease. “Since a mouse lives an average of two years, and humans an average of 80 years, one questions the reliability of using mice exhibiting Alzheimer’s symptoms to find drugs that will work in humans,” explains Jackson. “Biologically there are big differences.”

Anne Bang, Ph.D., director of cell biology at the Prebys Center, agrees. “A drug that works in mice sometimes doesn’t work in humans. Being able to grow human neurons in a dish provides a completely new approach to modeling neurological disease and searching for drugs, which actually takes into account the complexity of human genetics contributing to disease severity and risk.”

RISKS WORTH TAKING The Prebys Center is known for taking on innovative, high-risk projects that most drug discovery companies won’t pursue. These are the projects that may lead to important breakthroughs and innovative therapeutics. For

their current investigations into neurological disorders, Jackson and Bang have found equally ambitious partners.

an unprecedented opportunity for advancing our knowledge about these difficult-to-treat neurological conditions.

Jackson’s team is partnering with the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto to find potential treatments for Alzheimer’s, Parkinson’s and other neurodegenerative conditions.

“Many people question if the biological processes we are targeting can even be affected with a drug,” he says. “But we believe in taking risks and using technology to push the boundaries to find drugs that could make the risks worth taking. We won’t know if it’s possible unless we try.”

“The industrial-scale capabilities of the Prebys Center really support the team’s investigations. Having the sort of high-throughput automation that we have here—for validation, reproducibility and drug target discovery—is invaluable,” Bang explains.

Bang is using the “disease in a dish” strategy to unravel the mechanisms behind two other complex neurological conditions, bipolar disorder and schizophrenia.

She is collaborating with partners across the nation under a five-year, $15.4 million grant from the National Institutes of Health (NIH) that teams SBP with Johns Hopkins, the Salk Institute, the University of Michigan and two industry partners, Janssen Research & Development and Cellular Dynamics International.

“Being able to grow various types of patient-specific, disease-relevant human neurons that can be studied under controlled conditions offers

IT TAKES PASSION It can take years from growing a neuron to developing a prototype drug—so what keeps researchers inspired? “Actually, it’s fascinating work,” Bang says. “I’m addicted to getting answers to my questions.”

Adds Jackson, “These risky projects either appeal to you or they don’t.

But to achieve success you have to explore lots of different avenues— you develop a drug-hunter mentality, accept the risk and stay motivated by keeping patient needs firmly in focus at all times.

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PATHWAYS

SUMMER 2017

DONORS

COLLABORATION

Karen and Stuart Tanz: Getting to the Finish Line Faster

The SBP-GSK Center for Translational Neuroscience Last year, GlaxoSmithKline (GSK) teamed up with our Institute to create the SBP-GSK Center for Translational Neuroscience. The Center is designed to advance research into difficult neurodegenerative diseases such as Alzheimer’s and other dementias and bring together experts from SBP and GSK to investigate factors that influence brain function and potentially reverse or slow down neurodegeneration.

The aim is to identify and validate new therapeutic targets and bolster research dedicated to translational neuroscience.

Scientists from the Tanz Initiative gather with the Tanz family Front Row: Huaxi Xu, Ph.D., Peter St. George-Hyslop, M.D., Stuart & Karen Tanz, Eduard Sergienko, Ph.D., Elena Pasquale, Ph.D., Paul Fraser, M.D. Second Row: Zach Tanz, Alban Espiasse, Michael Jackson, Ph.D., Sarah Hudson, Ph.D. Third Row: Anne Bang, Ph.D., Artur Cane, Sirkku Pollari, Ph.D., Deborah Pre, Ph.D., Yingjun Zhao, Ph.D.

Thanks to the philanthropic vision of Stuart and Karen Tanz, Sanford Burnham Prebys Medical Discovery Institute (SBP) and the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases have combined their strengths in a unique collaboration to find new treatments for diseases such as Alzheimer’s, dementia and Parkinson’s.

The couple discuss their motivation and why selecting SBP as a partner in research and drug discovery will speed results.

Q: What sparked your interest in neurodegeneration?

Stuart Tanz: It goes back to my father, Mark Tanz, who built one of the great research centers in Canada. That sparked my interest in medicine. I witnessed firsthand my grandmother Gertrude, or Gertie, as we called her, suffer and decline from Alzheimer’s disease. She passed away in June 1986, while she was in her early 80s. It was sad to see such a sharp, vibrant matriarch slowly and then very rapidly decline.

Karen Tanz: We’re doing this for the next generation. We have a granddaughter now who’s two years old. We want her to grow up in a world where there is hope—and treatments—for patients who are at risk of developing these devastating diseases.

Q: Why did you select SBP? Karen Tanz: It was such an organic, complementary combination of strengths.

The University of Toronto has strong research and clinical units. And SBP is amazing. It’s known for taking it to the next level, that is, taking what we learn from research and turning it into

drug discovery in the Conrad Prebys Center for Chemical Genomics (Prebys Center). The robotics technology is so impressive—thousands of drugs can be screened very quickly.

I just love how this place works. It’s less bureaucratic than other research institutes. Stuart, being the businessman, wants results now.

Stuart Tanz: I posed the question—how are we going to get to the finish line?

SBP proposed that we combine the efforts of both organizations to get to the finish line faster. We’re taking the brightest from two world-renowned institutions and bringing them together with the Tanz Initiative.

Q: What motivates your philanthropy?

Stuart Tanz: We’ve been so lucky in the business world, just being in the right place at the right time. We want to be able to give back and share our success with others. This initiative can achieve much more than the accomplishments of two great institutions separately. As they say in the world of Wall Street, one plus one can be greater than three.

According to Min Li, Ph.D., SVP, global head of neurosciences at GSK, “Neurodegenerative diseases cross many fields of science, and this partnership takes full advantage of the depth and breadth of expertise in both organizations to advance our shared mission of helping patients through the discovery of new medicines.”

GSK’s expertise in neuroscience includes the Neurosciences Therapy Area Unit (NSTAU)—which in addition to the Center in San Diego, has locations in Shanghai (China), Philadelphia (U.S.), and London (UK). The NSTAU focuses on neurodegenerative and neuroexcitatory disorders and seeks to deliver clinically transformative and commercially performing medicines by intervening in fundamental nerve function.

GSK recently appointed Paul Wren, Ph.D., senior director neurosciences at GSK, to lead GSK’s partnership in the collaboration with SBP scientists and will be based at the Center in San Diego.

The SBP-GSK Center for Translational Neuroscience is one more sign of a growing emphasis on neuroscience at our Institute.

“This unique alliance provides an opportunity to combine the complimentary expertise of scientists from both organizations to address one of the greatest unmet needs of our society today.”

Perry Nisen, M.D., Ph.D., CEO of SBP

Center for Translational Neuroscience

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18

PATHWAYS

SUMMER 2017

DONORS

COLLABORATION

Karen and Stuart Tanz: Getting to the Finish Line Faster

The SBP-GSK Center for Translational Neuroscience Last year, GlaxoSmithKline (GSK) teamed up with our Institute to create the SBP-GSK Center for Translational Neuroscience. The Center is designed to advance research into difficult neurodegenerative diseases such as Alzheimer’s and other dementias and bring together experts from SBP and GSK to investigate factors that influence brain function and potentially reverse or slow down neurodegeneration.

The aim is to identify and validate new therapeutic targets and bolster research dedicated to translational neuroscience.

Scientists from the Tanz Initiative gather with the Tanz family Front Row: Huaxi Xu, Ph.D., Peter St. George-Hyslop, M.D., Stuart & Karen Tanz, Eduard Sergienko, Ph.D., Elena Pasquale, Ph.D., Paul Fraser, M.D. Second Row: Zach Tanz, Alban Espiasse, Michael Jackson, Ph.D., Sarah Hudson, Ph.D. Third Row: Anne Bang, Ph.D., Artur Cane, Sirkku Pollari, Ph.D., Deborah Pre, Ph.D., Yingjun Zhao, Ph.D.

Thanks to the philanthropic vision of Stuart and Karen Tanz, Sanford Burnham Prebys Medical Discovery Institute (SBP) and the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases have combined their strengths in a unique collaboration to find new treatments for diseases such as Alzheimer’s, dementia and Parkinson’s.

The couple discuss their motivation and why selecting SBP as a partner in research and drug discovery will speed results.

Q: What sparked your interest in neurodegeneration?

Stuart Tanz: It goes back to my father, Mark Tanz, who built one of the great research centers in Canada. That sparked my interest in medicine. I witnessed firsthand my grandmother Gertrude, or Gertie, as we called her, suffer and decline from Alzheimer’s disease. She passed away in June 1986, while she was in her early 80s. It was sad to see such a sharp, vibrant matriarch slowly and then very rapidly decline.

Karen Tanz: We’re doing this for the next generation. We have a granddaughter now who’s two years old. We want her to grow up in a world where there is hope—and treatments—for patients who are at risk of developing these devastating diseases.

Q: Why did you select SBP? Karen Tanz: It was such an organic, complementary combination of strengths.

The University of Toronto has strong research and clinical units. And SBP is amazing. It’s known for taking it to the next level, that is, taking what we learn from research and turning it into

drug discovery in the Conrad Prebys Center for Chemical Genomics (Prebys Center). The robotics technology is so impressive—thousands of drugs can be screened very quickly.

I just love how this place works. It’s less bureaucratic than other research institutes. Stuart, being the businessman, wants results now.

Stuart Tanz: I posed the question—how are we going to get to the finish line?

SBP proposed that we combine the efforts of both organizations to get to the finish line faster. We’re taking the brightest from two world-renowned institutions and bringing them together with the Tanz Initiative.

Q: What motivates your philanthropy?

Stuart Tanz: We’ve been so lucky in the business world, just being in the right place at the right time. We want to be able to give back and share our success with others. This initiative can achieve much more than the accomplishments of two great institutions separately. As they say in the world of Wall Street, one plus one can be greater than three.

According to Min Li, Ph.D., SVP, global head of neurosciences at GSK, “Neurodegenerative diseases cross many fields of science, and this partnership takes full advantage of the depth and breadth of expertise in both organizations to advance our shared mission of helping patients through the discovery of new medicines.”

GSK’s expertise in neuroscience includes the Neurosciences Therapy Area Unit (NSTAU)—which in addition to the Center in San Diego, has locations in Shanghai (China), Philadelphia (U.S.), and London (UK). The NSTAU focuses on neurodegenerative and neuroexcitatory disorders and seeks to deliver clinically transformative and commercially performing medicines by intervening in fundamental nerve function.

GSK recently appointed Paul Wren, Ph.D., senior director neurosciences at GSK, to lead GSK’s partnership in the collaboration with SBP scientists and will be based at the Center in San Diego.

The SBP-GSK Center for Translational Neuroscience is one more sign of a growing emphasis on neuroscience at our Institute.

“This unique alliance provides an opportunity to combine the complimentary expertise of scientists from both organizations to address one of the greatest unmet needs of our society today.”

Perry Nisen, M.D., Ph.D., CEO of SBP

Center for Translational Neuroscience

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PATHWAYS

SUMMER 2017

SBP PEOPLE

Q. How did you get started in philanthropy?

Connecting Individuals to Causes Andrea Davidson, the new vice president of Philanthropy, wants to ensure Sanford Burnham Prebys Medical Discovery Institute (SBP) has the resources to continue making discoveries that benefit human health.

Andrea Davidson and her dog, Otis

A. M y mother worked in philanthropy and encouraged me to explore the field as a career. She loved connecting donors to causes.

I’ve often felt that if my father and grandfather, who both died of heart disease when they were young, were alive today, they might have had access to more effective drugs that are now available, thanks to advances in medicine.

21

EVENTS

Bringing It

for SBP!

These experiences have colored my view of philanthropy—to me it’s all about connecting people with their passions and hopes for scientific discoveries that will improve human health.

Q. What keeps you motivated to continue in the field?

A. M any donors give because they’ve had a personal experience with a disease themselves or with a loved one, and they are driven to do what they can to eradicate a disease or improve the life of those afflicted with it. Listening to stories from donors about why they give is inspirational.

Q. What attracted you to SBP? A. T here aren’t a lot of places like SBP. It’s unique because of the combined emphasis on making breakthrough research discoveries and then translating that science into meaningful preventions, diagnostics, treatments and cures that benefit patients.

The breadth of research programs here—cancer, immunology, neuroscience, metabolism and rare diseases—is also a bonus because there is ample opportunity for scientific cross-talk that can spur “eureka” moments between scientists from different disciplines.

Finally, the drug discovery capabilities at the Conrad Prebys Center for Chemical Genomics (Prebys Center), probably the most sophisticated in the nonprofit research world, puts SBP in the top tier of institutions that can truly have an impact on human health. It’s an amazing place to be.

Q. H ow will philanthropy support SBP’s work to translate discoveries for the benefit of patients?

A. P hilanthropy plays an increasingly critical role in biomedical research as grant money gets tighter. I want to create a sustainable source of philanthropic funding for our scientists who are doing critical work to combat some of the most debilitating diseases.

With the Philanthropy team, I’m going to be working to expand our donor base and build a future pipeline of supporters. Because SBP’s mission and vision are relevant worldwide, we have an opportunity within as well as outside of San Diego to raise funds.

Q. W hat have you learned from your significant experience in fundraising that will be important at SBP?

Following an 11-year career at UC San Diego in development, Andrea joined SBP in February.

A. A t the end of the day, the connection to a cause flourishes when there is a strong relationship between an individual and a particular organization. Donors give to institutions they trust and have confidence in. The more connected an individual is with the organization, the more passionate they feel about supporting it.

Jermey Stallings kicks it up at Bring It!

In one of the most unique events in the San Diego area, nearly 300 people came together for “Bring It!”—a gameshow-style “fun-raiser” at the Del Mar Fairgrounds in April. The weird science-themed event raised money for our Institute and gave guests a rare opportunity to relive the 1980’s.

20

PATHWAYS

SUMMER 2017

SBP PEOPLE

Q. How did you get started in philanthropy?

Connecting Individuals to Causes Andrea Davidson, the new vice president of Philanthropy, wants to ensure Sanford Burnham Prebys Medical Discovery Institute (SBP) has the resources to continue making discoveries that benefit human health.

Andrea Davidson and her dog, Otis

A. M y mother worked in philanthropy and encouraged me to explore the field as a career. She loved connecting donors to causes.

I’ve often felt that if my father and grandfather, who both died of heart disease when they were young, were alive today, they might have had access to more effective drugs that are now available, thanks to advances in medicine.

21

EVENTS

Bringing It

for SBP!

These experiences have colored my view of philanthropy—to me it’s all about connecting people with their passions and hopes for scientific discoveries that will improve human health.

Q. What keeps you motivated to continue in the field?

A. M any donors give because they’ve had a personal experience with a disease themselves or with a loved one, and they are driven to do what they can to eradicate a disease or improve the life of those afflicted with it. Listening to stories from donors about why they give is inspirational.

Q. What attracted you to SBP? A. T here aren’t a lot of places like SBP. It’s unique because of the combined emphasis on making breakthrough research discoveries and then translating that science into meaningful preventions, diagnostics, treatments and cures that benefit patients.

The breadth of research programs here—cancer, immunology, neuroscience, metabolism and rare diseases—is also a bonus because there is ample opportunity for scientific cross-talk that can spur “eureka” moments between scientists from different disciplines.

Finally, the drug discovery capabilities at the Conrad Prebys Center for Chemical Genomics (Prebys Center), probably the most sophisticated in the nonprofit research world, puts SBP in the top tier of institutions that can truly have an impact on human health. It’s an amazing place to be.

Q. H ow will philanthropy support SBP’s work to translate discoveries for the benefit of patients?

A. P hilanthropy plays an increasingly critical role in biomedical research as grant money gets tighter. I want to create a sustainable source of philanthropic funding for our scientists who are doing critical work to combat some of the most debilitating diseases.

With the Philanthropy team, I’m going to be working to expand our donor base and build a future pipeline of supporters. Because SBP’s mission and vision are relevant worldwide, we have an opportunity within as well as outside of San Diego to raise funds.

Q. W hat have you learned from your significant experience in fundraising that will be important at SBP?

Following an 11-year career at UC San Diego in development, Andrea joined SBP in February.

A. A t the end of the day, the connection to a cause flourishes when there is a strong relationship between an individual and a particular organization. Donors give to institutions they trust and have confidence in. The more connected an individual is with the organization, the more passionate they feel about supporting it.

Jermey Stallings kicks it up at Bring It!

In one of the most unique events in the San Diego area, nearly 300 people came together for “Bring It!”—a gameshow-style “fun-raiser” at the Del Mar Fairgrounds in April. The weird science-themed event raised money for our Institute and gave guests a rare opportunity to relive the 1980’s.

22

PATHWAYS

SUMMER 2017

23

NOBEL SPONSOR

Guests in the 1980’s vibe

CURIOSITY SPONSOR

THE MOST FUN EVENT EVER “It certainly was,” said Juli Oh, co-committee co-chair.

Fellow committee co-chair Matt Browne came on stage to rap a few lines from the Beastie Boys, cheered on by two other co-chairs, Sarah and David Szekeres.

Tables competed in heated trivia rounds, and guests braved the stage for hilarious challenges, such as “Hungry Hungry Human” (the Homo sapiens version of the Hungry Hungry Hippo game).

Hungry Human game time The Danaher Corporation takes the Grand Prize.

Guests played Pac-Man, chowed down on poke in petri dishes, knocked back cryo mojitos, and ended on sweet notes such as mini cupcakes with elements from the periodic table and glowin-the-dark cotton candy.

SCIENCE SPONSORS

Emcee John Weisbarth hosted the event with a rad ‘80s cover band. SBP scientist Brooke Emerling, Ph.D., talked about her research on breast and ovarian cancers and shared the story of how she is inspired to help a childhood friend, a 40-year-old single mom suffering from an aggressive form of breast cancer.

INNOVATION SPONSOR

Marleigh and Alan Gleicher

Guests came dressed in neon, the 1980 U.S. Olympic-winning ice hockey team, Madonna outfits, and characters from “Ferris Bueller’s Day Off” and “Miami Vice.”

RESEARCH SPONSORS

“This is a wonderful, wonderful nonprofit. If anyone actually wants to help patients, this is the place to start,” David Szekeres said in an interview.

Co-chairs Matt Browne, Juli Oh, Sarah and David Szekeres

ReFlow Team

Charles Patton Elizabeth Schwarzbach Retrophin Team

Jonell and Gregory Tibbitts Julie and Court Turner

Marleigh and Alan Gleicher

NuVasive Team

22

PATHWAYS

SUMMER 2017

23

NOBEL SPONSOR

Guests in the 1980’s vibe

CURIOSITY SPONSOR

THE MOST FUN EVENT EVER “It certainly was,” said Juli Oh, co-committee co-chair.

Fellow committee co-chair Matt Browne came on stage to rap a few lines from the Beastie Boys, cheered on by two other co-chairs, Sarah and David Szekeres.

Tables competed in heated trivia rounds, and guests braved the stage for hilarious challenges, such as “Hungry Hungry Human” (the Homo sapiens version of the Hungry Hungry Hippo game).

Hungry Human game time The Danaher Corporation takes the Grand Prize.

Guests played Pac-Man, chowed down on poke in petri dishes, knocked back cryo mojitos, and ended on sweet notes such as mini cupcakes with elements from the periodic table and glowin-the-dark cotton candy.

SCIENCE SPONSORS

Emcee John Weisbarth hosted the event with a rad ‘80s cover band. SBP scientist Brooke Emerling, Ph.D., talked about her research on breast and ovarian cancers and shared the story of how she is inspired to help a childhood friend, a 40-year-old single mom suffering from an aggressive form of breast cancer.

INNOVATION SPONSOR

Marleigh and Alan Gleicher

Guests came dressed in neon, the 1980 U.S. Olympic-winning ice hockey team, Madonna outfits, and characters from “Ferris Bueller’s Day Off” and “Miami Vice.”

RESEARCH SPONSORS

“This is a wonderful, wonderful nonprofit. If anyone actually wants to help patients, this is the place to start,” David Szekeres said in an interview.

Co-chairs Matt Browne, Juli Oh, Sarah and David Szekeres

ReFlow Team

Charles Patton Elizabeth Schwarzbach Retrophin Team

Jonell and Gregory Tibbitts Julie and Court Turner

Marleigh and Alan Gleicher

NuVasive Team

24

PATHWAYS

SUMMER 2017

LEGACY

When Gridiron Gives

Jim and Mary Jane Wiesler are planning for a future long after they are gone As Jim Wielser approaches his 90th birthday in July, the former Bank of America executive’s beliefs about Sanford Burnham Prebys Medical Discovery Institute (SBP) are as steadfast as his career.

The Wieslers are members of SBP’s Legacy Society, an invested group of donors who believe in our Institute’s mission of conducting basic research with a clear line-of-sight to better patient treatments for the future.

Q: Why is SBP a good philanthropic investment?

A: I ’ve been friends with Malin Burnham, an honorary trustee of SBP, since the third grade. We played football together at Point Loma High School, and we were known as the Gridiron Gang. We were in each other’s weddings. I trust Malin. He’s been successful in business, as have Denny Sanford and Conrad Prebys. When Malin vouches for SBP, I know he’s made a sound decision.

Q: Why did you include SBP in your estate planning?

A: T here’s always a shortage of funds for any charity. We support a number of institutions that help education and health care. With SBP, I was impressed by the sense of stability. I want to give to an organization that will carry out my goals long after I’m gone.

Mary Jane and Jim Wiesler

“We are looking for a cure for cancer. Cancer has touched all of us. My mother died of cancer suddenly at the age of 70.”

Jim Wiesler

President’s Circle Donors – 2016 Sanford Burnham Prebys Medical Discovery Institute honors the following donors who generously supported science benefiting patients with a gift of $1,000 or more in 2016. $50,000 AND ABOVE

$25,000– $49,999

American Association for Cancer Research

Rocio and Lorenzo Berho Susan and James Blair Cooley LLP Michael R. Cunningham European Commission Florida Blue Illumina Lady Tata Memorial Trust Science, Technology and Research Support (STARS) The Helmsley Charitable Trust Mary Jane and James Wiesler

American Heart Association Nancy and Matthew Browar C3: Cancer Centers Council Capella Bioscience Ltd Clementia Pharmaceuticals, Inc. Crohn’s and Colitis Foundation of America Cure Alzheimer’s Fund Epstein Family Foundation Florida Breast Cancer Foundation Inc. The Bill & Melinda Gates Foundation Genentech, Inc. Gilbert J. Martin Foundation William Randolph Hearst Foundation Hervey Family Fund at The San Diego Foundation Hide and Seek Foundation Lynn and Blake Ingle International Society For Cardiology Translational Research James B. Pendleton Charitable Trust Jean Perkins Foundation Juvenile Diabetes Research Foundation International Larry Hillblom Foundation

Q: What are you most proud of in your career?

Geniya and Papa Doug Manchester

A: I spent my entire career at Bank of America, rising through the ranks to retire as vice-chairman and member of the managing committee. When I retired, I was looking forward to a relaxed retirement and spending lots of time with Mary Jane. Then the Greater San Diego Chamber of Commerce got into trouble and asked me to lead the organization. I said, “No, I promised my wife I would retire.” When I told Mary Jane, she said, “You have to do it!” So I became president, came in and rescued the organization.

Muscular Dystrophy Association

Q: What about your family life?

A: I ’ve been married to Mary Jane for 63 years. I met her when I was 24 years old and she was 20. I have been very blessed with three fabulous women in my life: my mother, my wife and a daughter whom I refer to as my favorite daughter, Ann. (He winks at Ann, who lives nearby and visits during the interview.) She’s my only daughter. We also have two amazing sons who live in New York and Sun Valley.

25

Pfizer Dinah and William* Ruch T. Denny Sanford St. Baldrick’s Foundation Karen and Stuart Tanz The Mary Kay Foundation Tobacco-Related Disease Research Program Todd & Karen Wanek Family Program for Hypoplastic Left Heart Richard P. Woltman

* Deceased

$10,000 – $24,999 Alexandria Real Estate Equities Axium Healthcare Richard Broida Roberta and Malin Burnham Mary and Adam Cherry Olivia and Peter Farrell Debby and Wainwright Fishburn Claudia Dunaway and Hudson Freeze Carol and John Gallagher Audrey S. Geisel Bill Gerhart Hanna and Mark Gleiberman Marleigh and Alan Gleicher Connie K. Golden Deana and Morley Golden Linda and David Hale Christine Infante and Robert L. Cushman Jeanne Jones and Don Breitenberg Marilena and Gregory Lucier National University Amy and Perry Nisen Robin and Hank Nordhoff NuVasive Inc. Milley Mai and Douglas Obenshain Retrophin, Inc. Linda Robertson and Roger Mills Stacy and Donald Rosenberg University of California, San Diego Kristiina Vuori

Donors

24

PATHWAYS

SUMMER 2017

LEGACY

When Gridiron Gives

Jim and Mary Jane Wiesler are planning for a future long after they are gone As Jim Wielser approaches his 90th birthday in July, the former Bank of America executive’s beliefs about Sanford Burnham Prebys Medical Discovery Institute (SBP) are as steadfast as his career.

The Wieslers are members of SBP’s Legacy Society, an invested group of donors who believe in our Institute’s mission of conducting basic research with a clear line-of-sight to better patient treatments for the future.

Q: Why is SBP a good philanthropic investment?

A: I ’ve been friends with Malin Burnham, an honorary trustee of SBP, since the third grade. We played football together at Point Loma High School, and we were known as the Gridiron Gang. We were in each other’s weddings. I trust Malin. He’s been successful in business, as have Denny Sanford and Conrad Prebys. When Malin vouches for SBP, I know he’s made a sound decision.

Q: Why did you include SBP in your estate planning?

A: T here’s always a shortage of funds for any charity. We support a number of institutions that help education and health care. With SBP, I was impressed by the sense of stability. I want to give to an organization that will carry out my goals long after I’m gone.

Mary Jane and Jim Wiesler

“We are looking for a cure for cancer. Cancer has touched all of us. My mother died of cancer suddenly at the age of 70.”

Jim Wiesler

President’s Circle Donors – 2016 Sanford Burnham Prebys Medical Discovery Institute honors the following donors who generously supported science benefiting patients with a gift of $1,000 or more in 2016. $50,000 AND ABOVE

$25,000– $49,999

American Association for Cancer Research

Rocio and Lorenzo Berho Susan and James Blair Cooley LLP Michael R. Cunningham European Commission Florida Blue Illumina Lady Tata Memorial Trust Science, Technology and Research Support (STARS) The Helmsley Charitable Trust Mary Jane and James Wiesler

American Heart Association Nancy and Matthew Browar C3: Cancer Centers Council Capella Bioscience Ltd Clementia Pharmaceuticals, Inc. Crohn’s and Colitis Foundation of America Cure Alzheimer’s Fund Epstein Family Foundation Florida Breast Cancer Foundation Inc. The Bill & Melinda Gates Foundation Genentech, Inc. Gilbert J. Martin Foundation William Randolph Hearst Foundation Hervey Family Fund at The San Diego Foundation Hide and Seek Foundation Lynn and Blake Ingle International Society For Cardiology Translational Research James B. Pendleton Charitable Trust Jean Perkins Foundation Juvenile Diabetes Research Foundation International Larry Hillblom Foundation

Q: What are you most proud of in your career?

Geniya and Papa Doug Manchester

A: I spent my entire career at Bank of America, rising through the ranks to retire as vice-chairman and member of the managing committee. When I retired, I was looking forward to a relaxed retirement and spending lots of time with Mary Jane. Then the Greater San Diego Chamber of Commerce got into trouble and asked me to lead the organization. I said, “No, I promised my wife I would retire.” When I told Mary Jane, she said, “You have to do it!” So I became president, came in and rescued the organization.

Muscular Dystrophy Association

Q: What about your family life?

A: I ’ve been married to Mary Jane for 63 years. I met her when I was 24 years old and she was 20. I have been very blessed with three fabulous women in my life: my mother, my wife and a daughter whom I refer to as my favorite daughter, Ann. (He winks at Ann, who lives nearby and visits during the interview.) She’s my only daughter. We also have two amazing sons who live in New York and Sun Valley.

25

Pfizer Dinah and William* Ruch T. Denny Sanford St. Baldrick’s Foundation Karen and Stuart Tanz The Mary Kay Foundation Tobacco-Related Disease Research Program Todd & Karen Wanek Family Program for Hypoplastic Left Heart Richard P. Woltman

* Deceased

$10,000 – $24,999 Alexandria Real Estate Equities Axium Healthcare Richard Broida Roberta and Malin Burnham Mary and Adam Cherry Olivia and Peter Farrell Debby and Wainwright Fishburn Claudia Dunaway and Hudson Freeze Carol and John Gallagher Audrey S. Geisel Bill Gerhart Hanna and Mark Gleiberman Marleigh and Alan Gleicher Connie K. Golden Deana and Morley Golden Linda and David Hale Christine Infante and Robert L. Cushman Jeanne Jones and Don Breitenberg Marilena and Gregory Lucier National University Amy and Perry Nisen Robin and Hank Nordhoff NuVasive Inc. Milley Mai and Douglas Obenshain Retrophin, Inc. Linda Robertson and Roger Mills Stacy and Donald Rosenberg University of California, San Diego Kristiina Vuori

Donors

26

PATHWAYS

SUMMER 2017

$1,000– $9,999

Demeter Therapeutics

Amy and Bill Koman

Cynthia and Aaron Shenkman

Carol and Thomas Dillon

Victory and Richard Lareau

The Simon-Strauss Foundation

Elizabeth and Darryl Albertson

Direct Electron, LP

Carol and George Lattimer

StemCell Technologies

Albireo Pharma, Inc.

Patti and Dave Down

Laura and Peter Leddy

Anthony Y. Sun

Karen L. Alexander

Natalie and David Dragotto

Reinette S. Levine

Ann Hollister and Jonathan Thomas

Alex’s Lemonade Stand Foundation for Childhood Cancer

Drusilla Farwell Foundation

Shirley and Gene Littler

Stephen B. Thomas

Lisa and Steven Altman

Barbara and Jim Dudl

Local Independent Charities of America

Molly McCormick Thornton

Nancy and James Eastman

Jill and Mark Lukavsky

Zuhre and Ahmet Tutuncu

Edison Pharmaceuticals Inc.

Neil F. McFarlane

Kathryn and Donald Vaughn

Stephanie and Michael Epstein

Mary and Jack McKinnon

Erna* and Andrew Viterbi

Terry Erb

Silvana and Alberto Michan

Crystal and Jonathan Vittetoe

Rebecca and Edward Etess

Lucille A. Miller

Joshua Vittetoe

Anne L. Evans

Dr. Howard and Barbara Milstein

Kathleen A. Wachter

Jennifer and Kurt Eve

Mizutani Foundation for Glycoscience

Peggy Walker-Conner

FEI Electron Optics

Marci and Ronald Morgan

Jennifer and Douglas Walner

Susan and Michael Finley

Bradley A. Morrice

Mary Walshok

Nina Fishman and Alan Attridge

Bruce A. Morrice

Randi and Charles Wax

Kaleen Lemmon and Arthur Fogel

NGLY1 Foundation

Tara and Charles Wegner

Joan and Archie Freitas

Michael P. Orlando

Ellen G. Weinstein

Angela and Dennis Friese

Denise Botticelli and Peter Pickslay

Judy and Jack* White

Michiko and Minoru Fukuda

Joan and Ben* Pollard

Armi and Albert Williams

Mary Ellen and Kieran Gallahue

Jori H. Potiker

Stephanie and Stephen Williams

GE Healthcare

Peggy and Peter Preuss

Karin E. Winner

John Goodman

Erin and Peter Preuss

Diana and Gabriel Wisdom

Anne-Marie Gordon

Qualcomm Inc.

Bebe L. Zigman

Gordon Ross Medical Foundation

Sue Raffee

Emma and Leo Zuckerman

Lynn Gorguze and Scott Peters

Nicole and Jim Reynolds

Lola and Walter Green

Ann Riner and John Conyers

Lisa Haile

Marilyn and Michael Rosen

Dennis J. Hammes

Liberty Ross

Susan and Paul Hering

Joyleen S. Rottenstein

Tammy and Lawrence Hershfield

Mary and Harold Sadler

Dodie and Loren Hinkelman

Beth and Norman Saks

Reena and Samuel Horowitz

Michael P. Sampson

Robyn Hudgens

Rupert M. Sanders

Margaret and Robert Hulter

Meredith and Richard Schoebel

International Stem Cell Corporation

Doreen and Myron Schonbrun

Debby and Hal Jacobs

Marie G. Schrup

JSciMed Central

Edward R. Schulak

Rupa and Harsh Karandikar

Elizabeth Schwarzbach

Joye Blount and Jessie J. Knight

Julie and Costa Sevastopoulos

Louise and Raymond Knowles

Jean and Gary Shekhter

American Federation for Aging Research Cindy and Stephen Aselage Sarah and Brian Bachman Alice and Roger Baggenstoss Bank of America Molly Jaeger Begent and David Begent Diane and Knox Bell Rachel and Dan Berdo Maggi and Alejandro Berho Betty and J.R.* Beyster Darcy and Robert Bingham Ruth Claire Black Ronne and Linden Blue Pamela Boynton

Donors

Kathleen and Roger Brinning Julie and George Bronstein Kathy and Ed Brown Cathe Burnham Sue and Howard Busby Adriana Cabre Pamela and Carl* Carter Tracey and Gary Chessum Linda Chester and Kenneth Rind Stephen J. Cohen Bess and Arthur Collias CONNECT Julie and Gordon Cooke Liz and Michael Copley Nancy F. Corbitt Pamela and Keith Cox Gigi and Edward* Cramer Christine Cunningham D Bar Isabel and Peter Dansky DAV, Inc

* Deceased

27

Donors

26

PATHWAYS

SUMMER 2017

$1,000– $9,999

Demeter Therapeutics

Amy and Bill Koman

Cynthia and Aaron Shenkman

Carol and Thomas Dillon

Victory and Richard Lareau

The Simon-Strauss Foundation

Elizabeth and Darryl Albertson

Direct Electron, LP

Carol and George Lattimer

StemCell Technologies

Albireo Pharma, Inc.

Patti and Dave Down

Laura and Peter Leddy

Anthony Y. Sun

Karen L. Alexander

Natalie and David Dragotto

Reinette S. Levine

Ann Hollister and Jonathan Thomas

Alex’s Lemonade Stand Foundation for Childhood Cancer

Drusilla Farwell Foundation

Shirley and Gene Littler

Stephen B. Thomas

Lisa and Steven Altman

Barbara and Jim Dudl

Local Independent Charities of America

Molly McCormick Thornton

Nancy and James Eastman

Jill and Mark Lukavsky

Zuhre and Ahmet Tutuncu

Edison Pharmaceuticals Inc.

Neil F. McFarlane

Kathryn and Donald Vaughn

Stephanie and Michael Epstein

Mary and Jack McKinnon

Erna* and Andrew Viterbi

Terry Erb

Silvana and Alberto Michan

Crystal and Jonathan Vittetoe

Rebecca and Edward Etess

Lucille A. Miller

Joshua Vittetoe

Anne L. Evans

Dr. Howard and Barbara Milstein

Kathleen A. Wachter

Jennifer and Kurt Eve

Mizutani Foundation for Glycoscience

Peggy Walker-Conner

FEI Electron Optics

Marci and Ronald Morgan

Jennifer and Douglas Walner

Susan and Michael Finley

Bradley A. Morrice

Mary Walshok

Nina Fishman and Alan Attridge

Bruce A. Morrice

Randi and Charles Wax

Kaleen Lemmon and Arthur Fogel

NGLY1 Foundation

Tara and Charles Wegner

Joan and Archie Freitas

Michael P. Orlando

Ellen G. Weinstein

Angela and Dennis Friese

Denise Botticelli and Peter Pickslay

Judy and Jack* White

Michiko and Minoru Fukuda

Joan and Ben* Pollard

Armi and Albert Williams

Mary Ellen and Kieran Gallahue

Jori H. Potiker

Stephanie and Stephen Williams

GE Healthcare

Peggy and Peter Preuss

Karin E. Winner

John Goodman

Erin and Peter Preuss

Diana and Gabriel Wisdom

Anne-Marie Gordon

Qualcomm Inc.

Bebe L. Zigman

Gordon Ross Medical Foundation

Sue Raffee

Emma and Leo Zuckerman

Lynn Gorguze and Scott Peters

Nicole and Jim Reynolds

Lola and Walter Green

Ann Riner and John Conyers

Lisa Haile

Marilyn and Michael Rosen

Dennis J. Hammes

Liberty Ross

Susan and Paul Hering

Joyleen S. Rottenstein

Tammy and Lawrence Hershfield

Mary and Harold Sadler

Dodie and Loren Hinkelman

Beth and Norman Saks

Reena and Samuel Horowitz

Michael P. Sampson

Robyn Hudgens

Rupert M. Sanders

Margaret and Robert Hulter

Meredith and Richard Schoebel

International Stem Cell Corporation

Doreen and Myron Schonbrun

Debby and Hal Jacobs

Marie G. Schrup

JSciMed Central

Edward R. Schulak

Rupa and Harsh Karandikar

Elizabeth Schwarzbach

Joye Blount and Jessie J. Knight

Julie and Costa Sevastopoulos

Louise and Raymond Knowles

Jean and Gary Shekhter

American Federation for Aging Research Cindy and Stephen Aselage Sarah and Brian Bachman Alice and Roger Baggenstoss Bank of America Molly Jaeger Begent and David Begent Diane and Knox Bell Rachel and Dan Berdo Maggi and Alejandro Berho Betty and J.R.* Beyster Darcy and Robert Bingham Ruth Claire Black Ronne and Linden Blue Pamela Boynton

Donors

Kathleen and Roger Brinning Julie and George Bronstein Kathy and Ed Brown Cathe Burnham Sue and Howard Busby Adriana Cabre Pamela and Carl* Carter Tracey and Gary Chessum Linda Chester and Kenneth Rind Stephen J. Cohen Bess and Arthur Collias CONNECT Julie and Gordon Cooke Liz and Michael Copley Nancy F. Corbitt Pamela and Keith Cox Gigi and Edward* Cramer Christine Cunningham D Bar Isabel and Peter Dansky DAV, Inc

* Deceased

27

Donors

28

PATHWAYS

SUMMER 2017

EDUCATION

Breakthroughs in Bipolar Disorder Graduate student Cameron Pernia is on a journey to expose the biology of mental illness

Growing up surrounded by science—with a grandfather who worked on the Manhattan Project, a mother who worked at NASA, and Carl Sagan occasionally filling the role of babysitter—Cameron Pernia’s interest in science was nurtured by those closest to him.

Today, Pernia is a graduate student exploring the biological underpinnings of human behavior in the laboratory of Evan Snyder, M.D., Ph.D., director of the Center for Stem Cells and Regenerative Medicine. Pernia’s research is advancing our understanding of bipolar disorder, a chronic brain condition characterized by manic “high” and depressive “low” episodes.

This poorly understood disease affects more than 5 million people in the U.S., and between 25 and 50 percent of those diagnosed attempt suicide at least once in their lives— making it one of the most lethal mental illnesses.

“There is a need to treat this disease as a genetic disease, rather than a learned behavior, which will hopefully alleviate some of the harmful stigma surrounding mental health,” says Pernia.

“Bipolar disorder may be attributable to ‘networkopathy,’ a condition driven by subtle aberrations in neuron signaling networks across the brain,” he explains. “This means that to understand the disease we need to see how different cells work together to cause changes in behavior.”

Studying large-scale brain interactions in the lab was nearly impossible until the Snyder lab’s breakthrough that creates a complex mixture of human brain cells from bipolar patients’ reprogrammed stem cells. By comparing the patient samples with healthy donors, Pernia has helped identify a protein called CRMP2 that plays a key role in bipolar pathology, and predicts response to lithium– the most prescribed drug to treat the disorder.

The research was recently published in the Proceedings of the National Academy of Sciences.

As Pernia completes his Ph.D., he reflects on the value of his research project, saying, “My research is part of a wave of studies trying to make translational discoveries for complex psychiatric diseases. Understanding how to fundamentally treat diseases goes hand in hand with understanding how the human brain, mind and consciousness operate at the cellular level.”

After graduation, he hopes to continue pursuing research that will improve the lives of the millions of patients with neurological disorders.

29

“There is a moral and scientific responsibility to help patients with bipolar disorder.”

Cameron Pernia

28

PATHWAYS

SUMMER 2017

EDUCATION

Breakthroughs in Bipolar Disorder Graduate student Cameron Pernia is on a journey to expose the biology of mental illness

Growing up surrounded by science—with a grandfather who worked on the Manhattan Project, a mother who worked at NASA, and Carl Sagan occasionally filling the role of babysitter—Cameron Pernia’s interest in science was nurtured by those closest to him.

Today, Pernia is a graduate student exploring the biological underpinnings of human behavior in the laboratory of Evan Snyder, M.D., Ph.D., director of the Center for Stem Cells and Regenerative Medicine. Pernia’s research is advancing our understanding of bipolar disorder, a chronic brain condition characterized by manic “high” and depressive “low” episodes.

This poorly understood disease affects more than 5 million people in the U.S., and between 25 and 50 percent of those diagnosed attempt suicide at least once in their lives— making it one of the most lethal mental illnesses.

“There is a need to treat this disease as a genetic disease, rather than a learned behavior, which will hopefully alleviate some of the harmful stigma surrounding mental health,” says Pernia.

“Bipolar disorder may be attributable to ‘networkopathy,’ a condition driven by subtle aberrations in neuron signaling networks across the brain,” he explains. “This means that to understand the disease we need to see how different cells work together to cause changes in behavior.”

Studying large-scale brain interactions in the lab was nearly impossible until the Snyder lab’s breakthrough that creates a complex mixture of human brain cells from bipolar patients’ reprogrammed stem cells. By comparing the patient samples with healthy donors, Pernia has helped identify a protein called CRMP2 that plays a key role in bipolar pathology, and predicts response to lithium– the most prescribed drug to treat the disorder.

The research was recently published in the Proceedings of the National Academy of Sciences.

As Pernia completes his Ph.D., he reflects on the value of his research project, saying, “My research is part of a wave of studies trying to make translational discoveries for complex psychiatric diseases. Understanding how to fundamentally treat diseases goes hand in hand with understanding how the human brain, mind and consciousness operate at the cellular level.”

After graduation, he hopes to continue pursuing research that will improve the lives of the millions of patients with neurological disorders.

29

“There is a moral and scientific responsibility to help patients with bipolar disorder.”

Cameron Pernia

30

PATHWAYS

SUMMER 2017

Kashton Genest was 7-weeks-old when he was diagnosed with Alagille syndrome.

SCIENCE BENEFITING PATIENTS

This Disease Has Not Been Forgotten Alagille syndrome takes center stage on Rare Disease Day There are no pink ribbons for Alagille syndrome. No corporatesponsored awareness campaigns, and no nationwide relays, walks and races. In fact, patients with Alagille syndrome run into doctors who haven’t heard of their disease.

But on February 24, 2017, Alagille syndrome took center stage—thanks to the 8th annual Rare Disease Day symposium at Sanford Burnham Prebys Medical Discovery Institute (SBP). The SBP symposium series highlights a rare disease each year, and this year’s event was the first-ever scientific meeting to focus on Alagille (al-uh-GEEL) syndrome, a rare genetic disorder that occurs in one in 30,000 births.

“I wanted to organize a meeting where patients could come and see that there are many scientists out there who care about

31

this disease and are pushing for a cure,” says Duc Dong, Ph.D., assistant professor at SBP and the 2017 symposium chair. “I wanted them to realize that there is hope, that this disease has not been forgotten.”

TODAY: NO CURE Babies born with Alagille syndrome have too few bile ducts—which are essential for the transport of waste out of the liver. This causes liver damage, and consequently, toxins to build up in the blood, leading to constant, severe itching. Alagille syndrome patients can also have many

30

PATHWAYS

SUMMER 2017

Kashton Genest was 7-weeks-old when he was diagnosed with Alagille syndrome.

SCIENCE BENEFITING PATIENTS

This Disease Has Not Been Forgotten Alagille syndrome takes center stage on Rare Disease Day There are no pink ribbons for Alagille syndrome. No corporatesponsored awareness campaigns, and no nationwide relays, walks and races. In fact, patients with Alagille syndrome run into doctors who haven’t heard of their disease.

But on February 24, 2017, Alagille syndrome took center stage—thanks to the 8th annual Rare Disease Day symposium at Sanford Burnham Prebys Medical Discovery Institute (SBP). The SBP symposium series highlights a rare disease each year, and this year’s event was the first-ever scientific meeting to focus on Alagille (al-uh-GEEL) syndrome, a rare genetic disorder that occurs in one in 30,000 births.

“I wanted to organize a meeting where patients could come and see that there are many scientists out there who care about

31

this disease and are pushing for a cure,” says Duc Dong, Ph.D., assistant professor at SBP and the 2017 symposium chair. “I wanted them to realize that there is hope, that this disease has not been forgotten.”

TODAY: NO CURE Babies born with Alagille syndrome have too few bile ducts—which are essential for the transport of waste out of the liver. This causes liver damage, and consequently, toxins to build up in the blood, leading to constant, severe itching. Alagille syndrome patients can also have many

32

PATHWAYS

SUMMER 2017

33

SCIENCE BENEFITING PATIENTS

Doctors may go years without seeing a rare disease, but they affect between 25 and 30 million Americans, and at least 50% of them are children.

Source: National Institutes of Health

other developmental defects throughout their body, including the heart, kidneys, vertebrae, blood vessels and face.

RARE STATISTICS: There are more than 7,000 different types of rare diseases.

In the U.S., a condition is “rare” if it affects fewer than

200,000 people.

1 IN 10 Americans are living with a rare disease

30% OF CHILDREN with a rare disease will not live to see their 5th birthday

Source: Global Genes

There is no cure for this lifethreatening disease, and half of all patients need a liver transplant before adulthood.

Better treatments are desperately needed. Until this scientific meeting, there has been little discussion about working toward a cure for this genetic disease.

More than 100 people attended the event at the La Jolla campus, including clinicians, patients and families. Most attendees, however, were researchers who are interested in Alagille syndrome science and were eager to hear from fellow scientists about their challenges and discoveries related to the disease.

Dong was one of those researchers.

CONNECTIONS “In some ways, organizing this meeting was partly selfish,” he says. “I wanted to gather all the people studying various aspects of this disease so I could learn from them, share our lab’s recent discoveries and establish a more connected Alagille syndrome research community.”

Dong and his team have been studying JAGGED1, the gene implicated in Alagille syndrome.

Taking advantage of an unusual animal model, the zebrafish, they were able to uncover a novel genetic mechanism for the disease—opening new potential therapeutic avenues.

Further, his team surprisingly discovered that the bile ducts lost can be regenerated after they turned the affected gene back “on.”

“The implication is that these developmental defects in Alagille syndrome patients could potentially be reversible and that this disease may be treated by gene therapy,” he explains.

LOOKING AHEAD Much more research is needed, but as a result of the meeting, Dong and fellow scientists have already formed new collaborations. There are also plans to make a scientific Alagille syndrome meeting an annual event, held at rotating locales around the country.

“These meetings give a rare disease a huge boost, not just in recognition but in science,” Dong says. “It’s a day that we push the field forward and try to move closer to a cure.”

Duc Dong, Ph.D., an assistant professor in the Human Genetics Program, among the zebrafish tanks.

From Sci-Fi to Science

Can a zebra change its stripes?

The old saying says no, but for Duc Dong, Ph.D., the answer is a resounding yes.

“Mature cells appear to have the potential to convert into any other cell type,” says Dong, assistant professor at Sanford Burnham Prebys Medical Discovery Institute (SBP). “The dogma is that as cells mature and become different lineages—an eye cell, a gut cell and so on—they lose their potential to become something else. But we’re starting to see that their potential to adopt completely different identities is still there, even while they remain in the body, within highly specialized tissues.”

Dong’s goal is to unlock that potential—not to change a zebra’s stripes, but to advance regenerative medicine. In the lab, he and his team are developing technologies to reprogram dispensable cells such as skin, vasculature and fat cells so they transform into “replacement cells”—such as insulin-producing cells for diabetics, or dopamineproducing neurons for patients with Parkinson’s disease.

What’s more, the team is making these transformations happen not in a petri dish, but in vivo—inside a

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SCIENCE BENEFITING PATIENTS

Doctors may go years without seeing a rare disease, but they affect between 25 and 30 million Americans, and at least 50% of them are children.

Source: National Institutes of Health

other developmental defects throughout their body, including the heart, kidneys, vertebrae, blood vessels and face.

RARE STATISTICS: There are more than 7,000 different types of rare diseases.

In the U.S., a condition is “rare” if it affects fewer than

200,000 people.

1 IN 10 Americans are living with a rare disease

30% OF CHILDREN with a rare disease will not live to see their 5th birthday

Source: Global Genes

There is no cure for this lifethreatening disease, and half of all patients need a liver transplant before adulthood.

Better treatments are desperately needed. Until this scientific meeting, there has been little discussion about working toward a cure for this genetic disease.

More than 100 people attended the event at the La Jolla campus, including clinicians, patients and families. Most attendees, however, were researchers who are interested in Alagille syndrome science and were eager to hear from fellow scientists about their challenges and discoveries related to the disease.

Dong was one of those researchers.

CONNECTIONS “In some ways, organizing this meeting was partly selfish,” he says. “I wanted to gather all the people studying various aspects of this disease so I could learn from them, share our lab’s recent discoveries and establish a more connected Alagille syndrome research community.”

Dong and his team have been studying JAGGED1, the gene implicated in Alagille syndrome.

Taking advantage of an unusual animal model, the zebrafish, they were able to uncover a novel genetic mechanism for the disease—opening new potential therapeutic avenues.

Further, his team surprisingly discovered that the bile ducts lost can be regenerated after they turned the affected gene back “on.”

“The implication is that these developmental defects in Alagille syndrome patients could potentially be reversible and that this disease may be treated by gene therapy,” he explains.

LOOKING AHEAD Much more research is needed, but as a result of the meeting, Dong and fellow scientists have already formed new collaborations. There are also plans to make a scientific Alagille syndrome meeting an annual event, held at rotating locales around the country.

“These meetings give a rare disease a huge boost, not just in recognition but in science,” Dong says. “It’s a day that we push the field forward and try to move closer to a cure.”

Duc Dong, Ph.D., an assistant professor in the Human Genetics Program, among the zebrafish tanks.

From Sci-Fi to Science

Can a zebra change its stripes?

The old saying says no, but for Duc Dong, Ph.D., the answer is a resounding yes.

“Mature cells appear to have the potential to convert into any other cell type,” says Dong, assistant professor at Sanford Burnham Prebys Medical Discovery Institute (SBP). “The dogma is that as cells mature and become different lineages—an eye cell, a gut cell and so on—they lose their potential to become something else. But we’re starting to see that their potential to adopt completely different identities is still there, even while they remain in the body, within highly specialized tissues.”

Dong’s goal is to unlock that potential—not to change a zebra’s stripes, but to advance regenerative medicine. In the lab, he and his team are developing technologies to reprogram dispensable cells such as skin, vasculature and fat cells so they transform into “replacement cells”—such as insulin-producing cells for diabetics, or dopamineproducing neurons for patients with Parkinson’s disease.

What’s more, the team is making these transformations happen not in a petri dish, but in vivo—inside a

34

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SUMMER 2017

35

SCIENCE BENEFITING PATIENTS

“My vision is to cure diseases by taking biology in directions that evolution could not.”

Duc Dong, Ph.D.

FIVE REASONS TO STUDY ZEBRAFISH: Genetically similar to humans 1.

70% of human genes are found in zebrafish.

They have the same organs 2. as humans

Brain, heart, kidney, eyes, livers, nose, esophagus, intestines—to name a few.

3.

Easy to house

They are small and have simple living requirements.

Embryos are clear 4.

You can see fertilized eggs grow into baby fish under a microscope.

5.

Lots of eggs

Zebrafish have 200–300 offspring per pairing, providing a ready supply for research.

living organism and without the use of stem cells. Replacement cells generated in the body, as opposed to in artificial culture conditions, are believed to be safer and have greater functionality.

“What we’re asking is, ‘Can we change any cell into any other cell, all within the body?’” he explains.

“Because if you can, the sky’s the limit. You could make replacement cells and tissues for degenerative diseases and injuries,” Dong says.

“You could use that approach for almost any health problems that require replacement cells.”

AN INQUISITIVE MIND Dong’s path to his La Jolla lab and the cutting edge of developmental genetics began more than 8,000 miles away. Born in Vietnam, he and his siblings and parents were refugees who escaped the country by boat when Dong was 4. They later settled in Santa Clara, California, during the dawn of the Silicon Valley.

His family struggled, but Dong used his budding ingenuity to build his own toys and conduct scientific experiments on bugs. “All my failed experiments happened when I was a kid,” he says with a laugh. By his high school years, his team won Mars rover engineering contests sponsored by NASA. His inquisitive mind and affinity for science fiction (everything from Dr. Frankenstein to “Star Trek”) led him to pursue a career in biology. His first published paper as a graduate student included a sci-fi–like insect experiment: genetically inducing antennae, normally found on a fruit fly’s head, to grow out of other parts of the fly’s body.

After a postdoc at UC San Francisco, he joined SBP in 2008 and received the prestigious National Institutes of Health (NIH) Director’s New Innovator Award in 2012 to further advance his lineage reprogramming technologies in a vertebrate model.

HACKING A CELL He and his team are using zebrafish—tiny striped fish known for their regenerative abilities—as a model to reprogram cells into unrelated cell types, completely within the body of these living vertebrate animals.

The idea of reprogramming cells while they remain in the body might sound like science fiction, but there’s nothing fictional about it. Dong describes it as “hacking a cell,” and so far, the team has succeeded in “hacking” muscle and skin cells in zebrafish and converting them into pancreatic cells—just one step removed from pancreatic beta-cells, the insulinproducing cells lost in diabetics.

Using the same principle, they are very close to making neurons, and are also working on generating heart and liver cells.

Drawing from their expertise in developmental genetics, the team is also researching the genetic mechanisms of heritable diseases, including diabetes and Alagille syndrome, a neonatal disorder affecting the liver and other organs.

“I love finding answers to fundamental questions that people didn’t think to ask,” Dong says.

“These answers impact how we view and treat disease.”

SBP’s Rare Disease Day: What It Meant to Me

by Cindy Luxhoj

Participating in the Rare Disease Day Symposium on Alagille Syndrome (ALGS) at Sanford Burnham Prebys Medical Discovery Institute (SBP) was energizing, inspiring and, quite simply, pure joy for me. The day flew by as I marveled at the science, interacted with renown investigators, met new families in the ALGS community and reflected on how far research has progressed since the gene responsible for the disease, called Jagged 1, was identified in 1997, 20 long years ago.

I attended the Symposium in several capacities: as Executive Director of the Alagille Syndrome Alliance (ALGSA), which I founded in 1993; as a co-organizer of the Symposium, which the ALGSA proudly supported; and as a presenter sharing the story of ALGS Warriors, as we fondly

refer to our loved ones challenged by this devastating disease. And, most important, as a mother whose daughter, Alaina Hahn, braved the ALGS Warrior fight every day of her 24 years in this life.

To watch brilliant minds striving for answers, stretching their intellect and pushing the investigative envelope to its limits and beyond, is extraordinary. I left the Symposium confident that one day there will be a cure for this rare disease that dominated my daughter’s life and has been a driving force in mine for more than two decades.

It is too late for these discoveries to help Alaina. But research gives hope to countless ALGS Warriors and their loved ones, like me, who continue the battle and believe that one day, very soon, their lives will be free of the ravages of Alagille syndrome.

“To witness the important, groundbreaking work that is occurring at SBP, led by Dr. Duc Dong, is nothing short of miraculous. ” Cindy Luxhoj

“What we’ve learned from this work is that just a couple of genes can change a cell lineage to be something else entirely,” says Dong.

Cindy Luxhoj with her daughter Alaina

34

PATHWAYS

SUMMER 2017

35

SCIENCE BENEFITING PATIENTS

“My vision is to cure diseases by taking biology in directions that evolution could not.”

Duc Dong, Ph.D.

FIVE REASONS TO STUDY ZEBRAFISH: Genetically similar to humans 1.

70% of human genes are found in zebrafish.

They have the same organs 2. as humans

Brain, heart, kidney, eyes, livers, nose, esophagus, intestines—to name a few.

3.

Easy to house

They are small and have simple living requirements.

Embryos are clear 4.

You can see fertilized eggs grow into baby fish under a microscope.

5.

Lots of eggs

Zebrafish have 200–300 offspring per pairing, providing a ready supply for research.

living organism and without the use of stem cells. Replacement cells generated in the body, as opposed to in artificial culture conditions, are believed to be safer and have greater functionality.

“What we’re asking is, ‘Can we change any cell into any other cell, all within the body?’” he explains.

“Because if you can, the sky’s the limit. You could make replacement cells and tissues for degenerative diseases and injuries,” Dong says.

“You could use that approach for almost any health problems that require replacement cells.”

AN INQUISITIVE MIND Dong’s path to his La Jolla lab and the cutting edge of developmental genetics began more than 8,000 miles away. Born in Vietnam, he and his siblings and parents were refugees who escaped the country by boat when Dong was 4. They later settled in Santa Clara, California, during the dawn of the Silicon Valley.

His family struggled, but Dong used his budding ingenuity to build his own toys and conduct scientific experiments on bugs. “All my failed experiments happened when I was a kid,” he says with a laugh. By his high school years, his team won Mars rover engineering contests sponsored by NASA. His inquisitive mind and affinity for science fiction (everything from Dr. Frankenstein to “Star Trek”) led him to pursue a career in biology. His first published paper as a graduate student included a sci-fi–like insect experiment: genetically inducing antennae, normally found on a fruit fly’s head, to grow out of other parts of the fly’s body.

After a postdoc at UC San Francisco, he joined SBP in 2008 and received the prestigious National Institutes of Health (NIH) Director’s New Innovator Award in 2012 to further advance his lineage reprogramming technologies in a vertebrate model.

HACKING A CELL He and his team are using zebrafish—tiny striped fish known for their regenerative abilities—as a model to reprogram cells into unrelated cell types, completely within the body of these living vertebrate animals.

The idea of reprogramming cells while they remain in the body might sound like science fiction, but there’s nothing fictional about it. Dong describes it as “hacking a cell,” and so far, the team has succeeded in “hacking” muscle and skin cells in zebrafish and converting them into pancreatic cells—just one step removed from pancreatic beta-cells, the insulinproducing cells lost in diabetics.

Using the same principle, they are very close to making neurons, and are also working on generating heart and liver cells.

Drawing from their expertise in developmental genetics, the team is also researching the genetic mechanisms of heritable diseases, including diabetes and Alagille syndrome, a neonatal disorder affecting the liver and other organs.

“I love finding answers to fundamental questions that people didn’t think to ask,” Dong says.

“These answers impact how we view and treat disease.”

SBP’s Rare Disease Day: What It Meant to Me

by Cindy Luxhoj

Participating in the Rare Disease Day Symposium on Alagille Syndrome (ALGS) at Sanford Burnham Prebys Medical Discovery Institute (SBP) was energizing, inspiring and, quite simply, pure joy for me. The day flew by as I marveled at the science, interacted with renown investigators, met new families in the ALGS community and reflected on how far research has progressed since the gene responsible for the disease, called Jagged 1, was identified in 1997, 20 long years ago.

I attended the Symposium in several capacities: as Executive Director of the Alagille Syndrome Alliance (ALGSA), which I founded in 1993; as a co-organizer of the Symposium, which the ALGSA proudly supported; and as a presenter sharing the story of ALGS Warriors, as we fondly

refer to our loved ones challenged by this devastating disease. And, most important, as a mother whose daughter, Alaina Hahn, braved the ALGS Warrior fight every day of her 24 years in this life.

To watch brilliant minds striving for answers, stretching their intellect and pushing the investigative envelope to its limits and beyond, is extraordinary. I left the Symposium confident that one day there will be a cure for this rare disease that dominated my daughter’s life and has been a driving force in mine for more than two decades.

It is too late for these discoveries to help Alaina. But research gives hope to countless ALGS Warriors and their loved ones, like me, who continue the battle and believe that one day, very soon, their lives will be free of the ravages of Alagille syndrome.

“To witness the important, groundbreaking work that is occurring at SBP, led by Dr. Duc Dong, is nothing short of miraculous. ” Cindy Luxhoj

“What we’ve learned from this work is that just a couple of genes can change a cell lineage to be something else entirely,” says Dong.

Cindy Luxhoj with her daughter Alaina

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37

DISCOVERY HUB Flea infected with Yersinia pestis, which causes bubonic plague.

DISCOVERY HUB

Randal Kaufman, Ph.D., professor and director of the Degenerative Diseases Program

New Paths to Treating Visual Complications of Diabetes Up to 80 percent of people who have had diabetes for more than 20 years develop diabetic retinopathy, putting them at risk for vision loss. Current treatments for this complication have major drawbacks—laser therapy can cause blind spots, and biologic drugs are expensive.

A study in Science Translational Medicine reveals new steps in the development of diabetic retinopathy and shows that they can be prevented with drugs. Randal Kaufman, Ph.D., professor and director of the Degenerative Diseases Program, contributed to the research, in collaboration with Przemyslaw Sapieha, Ph.D., and Frédérick A. Mallette, Ph.D., at Maisonneuve-Rosemont Hospital and the Université de Montréal.

Late-stage retinopathy, with pathological vessel growth

“These findings suggest new ways to slow this devastating complication of diabetes,” said Kaufman. “Now that we know what happens inside retinal cells, therapies can be designed to address earlier steps in retinopathy progression.”

Repeated episodes of high blood sugar cause the blood vessels of the retina to become blocked. That can lead to the formation of weaker blood vessels in the interior of the eye that leak blood, block light and cause the retina to detach. Current therapies destroy the leaky vessels and keep more from growing.

2.5% of all people age 18 and older have diabetic retinopathy Source: Centers for Disease Control

The researchers found that retinal cells survive the initial loss of blood supply by going into a self-preservation mode called senescence.

Senescent cells secrete molecules that promote repair, including pro-vessel growth factors and cytokines.

The study identified two potential therapeutic strategies. First, the initiation of senescence can be blocked using inhibitors of inositolrequiring enzyme 1 alpha (IRE1alpha, discovered by Kaufman 20 years ago), which are being developed as anti-cancer treatments. Second, the secretion of growth factors and cytokines can be counteracted with eye injections of metformin, currently used in pill form to treat type 2 diabetes.

“Modulating senescence is a totally new way to treat retinopathy,” Kaufman commented.

“Our findings suggest that this strategy could be even better than current treatments at slowing the advance of the disease, and might even enhance patients’ vision.”

Combating the Threat of DrugResistant Plague The plague, also known as the Black Death, wiped out a third of Europe’s population in the 14th century and has a long history of exploitation as a biological weapon.

Even today, outbreaks of the disease, caused by the bacterium Yersinia pestis, persist in Asia and Africa and the southwestern U.S.

Without effective therapy, pneumonic plaque is usually fatal within

3 DAYS Source: World Health Organization

Although most plague is treatable if detected within hours of infection, the limited number of effective antibiotics, the emergence of antibiotic-resistant strains, the lack of an effective vaccine and the potential weaponization of aerosolized bacteria with bio-engineered antibiotic resistance all underscore the need to develop medical countermeasures. These factors have led the U.S. Department of Health and Human Services to designate Y. pestis as a Tier 1 Select Agent—the class reserved for pathogens that can be weaponized to kill millions of people.

“My lab is working on developing new ways to combat Y. pestis,” says Professor Francesca Marassi, Ph.D. “Understanding the basic mechanism of bacterial infection is the key first step.”

Finding new defenses against the Y. pestis microbe is important enough that Marassi’s research is being supported by a prestigious five-year grant from the National Institutes of Health.

Francesca Marassi, Ph.D. professor in the Cancer Metabolism and Signaling Networks Program

“We want to determine the architecture of the outer membrane surface of the bacterium because this is the first line of contact with the human host upon infection,” Marassi explains. “We’re studying a protein called Ail (adhesion invasion locus), which is exposed on the bacterial surface and interacts with human proteins in ways that help Y. pestis survive in blood—without Ail, bacterial virulence is highly attenuated.”

Marassi’s lab just made a key advance— developing methods to determine the structure of Ail in the membrane. The results are now published in the Journal of Biomolecular NMR. “These findings set the stage for studying the interactions of Ail with its protein partners on human host cells,” adds Marassi. “Being able to see the structure of Ail gives us vital insight for the development of drugs to fight the disease.”

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37

DISCOVERY HUB Flea infected with Yersinia pestis, which causes bubonic plague.

DISCOVERY HUB

Randal Kaufman, Ph.D., professor and director of the Degenerative Diseases Program

New Paths to Treating Visual Complications of Diabetes Up to 80 percent of people who have had diabetes for more than 20 years develop diabetic retinopathy, putting them at risk for vision loss. Current treatments for this complication have major drawbacks—laser therapy can cause blind spots, and biologic drugs are expensive.

A study in Science Translational Medicine reveals new steps in the development of diabetic retinopathy and shows that they can be prevented with drugs. Randal Kaufman, Ph.D., professor and director of the Degenerative Diseases Program, contributed to the research, in collaboration with Przemyslaw Sapieha, Ph.D., and Frédérick A. Mallette, Ph.D., at Maisonneuve-Rosemont Hospital and the Université de Montréal.

Late-stage retinopathy, with pathological vessel growth

“These findings suggest new ways to slow this devastating complication of diabetes,” said Kaufman. “Now that we know what happens inside retinal cells, therapies can be designed to address earlier steps in retinopathy progression.”

Repeated episodes of high blood sugar cause the blood vessels of the retina to become blocked. That can lead to the formation of weaker blood vessels in the interior of the eye that leak blood, block light and cause the retina to detach. Current therapies destroy the leaky vessels and keep more from growing.

2.5% of all people age 18 and older have diabetic retinopathy Source: Centers for Disease Control

The researchers found that retinal cells survive the initial loss of blood supply by going into a self-preservation mode called senescence.

Senescent cells secrete molecules that promote repair, including pro-vessel growth factors and cytokines.

The study identified two potential therapeutic strategies. First, the initiation of senescence can be blocked using inhibitors of inositolrequiring enzyme 1 alpha (IRE1alpha, discovered by Kaufman 20 years ago), which are being developed as anti-cancer treatments. Second, the secretion of growth factors and cytokines can be counteracted with eye injections of metformin, currently used in pill form to treat type 2 diabetes.

“Modulating senescence is a totally new way to treat retinopathy,” Kaufman commented.

“Our findings suggest that this strategy could be even better than current treatments at slowing the advance of the disease, and might even enhance patients’ vision.”

Combating the Threat of DrugResistant Plague The plague, also known as the Black Death, wiped out a third of Europe’s population in the 14th century and has a long history of exploitation as a biological weapon.

Even today, outbreaks of the disease, caused by the bacterium Yersinia pestis, persist in Asia and Africa and the southwestern U.S.

Without effective therapy, pneumonic plaque is usually fatal within

3 DAYS Source: World Health Organization

Although most plague is treatable if detected within hours of infection, the limited number of effective antibiotics, the emergence of antibiotic-resistant strains, the lack of an effective vaccine and the potential weaponization of aerosolized bacteria with bio-engineered antibiotic resistance all underscore the need to develop medical countermeasures. These factors have led the U.S. Department of Health and Human Services to designate Y. pestis as a Tier 1 Select Agent—the class reserved for pathogens that can be weaponized to kill millions of people.

“My lab is working on developing new ways to combat Y. pestis,” says Professor Francesca Marassi, Ph.D. “Understanding the basic mechanism of bacterial infection is the key first step.”

Finding new defenses against the Y. pestis microbe is important enough that Marassi’s research is being supported by a prestigious five-year grant from the National Institutes of Health.

Francesca Marassi, Ph.D. professor in the Cancer Metabolism and Signaling Networks Program

“We want to determine the architecture of the outer membrane surface of the bacterium because this is the first line of contact with the human host upon infection,” Marassi explains. “We’re studying a protein called Ail (adhesion invasion locus), which is exposed on the bacterial surface and interacts with human proteins in ways that help Y. pestis survive in blood—without Ail, bacterial virulence is highly attenuated.”

Marassi’s lab just made a key advance— developing methods to determine the structure of Ail in the membrane. The results are now published in the Journal of Biomolecular NMR. “These findings set the stage for studying the interactions of Ail with its protein partners on human host cells,” adds Marassi. “Being able to see the structure of Ail gives us vital insight for the development of drugs to fight the disease.”

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DISCOVERY HUB

39

DISCOVERY HUB

Xiao-Kun Zhang, Ph.D., adjunct professor in the Tumor Initiation and Maintenance Program Malene Hansen, Ph.D., professor in the Development, Aging and Regeneration Program

What Doesn’t Kill You Makes You Stronger Just about everyone knows that a little stress early in life makes you better able to handle similar challenges later, and biologists have found the same to be true for simple organisms and human cells. New findings from the lab of Malene Hansen, Ph.D., identify the cellular process that’s crucial to these benefits—one that’s also key for a long lifespan.

That process is autophagy, a means of recycling cells’ broken or unneeded parts to build new machinery and generate energy. Autophagy has been linked to longevity, in no small part because of research by Hansen’s group.

“We used C. elegans—tiny roundworms—to test the importance of autophagy in becoming stress resistant,” says Caroline Kumsta, Ph.D., staff scientist in Hansen’s lab and lead author of the study, published in Nature Communications.

C. elegans, 1 mm-long roundworms used to study aging

Kumsta and colleagues found that exposing worms to heat for one hour increased autophagy rates throughout the worms’ tissues. Heat treatment made normal worms better able to survive a longer incubation at the same temperatures a few days later, while worms deficient in autophagy failed to benefit.

The researchers reasoned that mild heat stress might improve the worms’ ability to handle another condition that worsens with

The average lifespan in the U.S. has increased from about 66 years in 1965 to about

76

years today Source: Centers for Disease Control

age—buildup of aggregated proteins, which damages cells. Exposing worms that make sticky proteins, similar to those that cause Huntington’s disease, to a mild heat shock reduced the number of protein aggregates.

In Huntington’s, protein clumping causes massive brain degeneration, which is eventually fatal.

“Our finding that brief heat exposure helps alleviate protein aggregation could lead to new approaches to slow the advance of neurodegenerative diseases,” says Hansen.

“A lot of people ask if this means they should go to the sauna or do hot yoga,” jokes Kumsta.

“That may not be a bad idea. But we have a lot more research to do to figure out whether that has anything to do with induction of autophagy by heat stress.”

New Research Explains How This Experimental Herb-derived Obesity Drug Works When a recent study identified a chemical found in an herb used in traditional Chinese medicine as a potential treatment for obesity, it made headlines. That’s because there are not yet any good ways to help obese people lose weight—the drugs that are available now work no better than diet and exercise, on average leading to a loss of only 5 percent of a person’s weight.

2.8 At least

million people die each year as a result of being overweight or obese.

Source: World Health Organization

Celastrol is a chemical compound isolated from the root extracts of the Thunder God Vine.

However, that study was only a first step— the molecular basis for the effects of the compound, called celastrol, was unknown. New research from the lab of Xiao-Kun Zhang, Ph.D., adjunct professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), identifies the receptor on which celastrol acts, and the cellular processes it alters.

people lose a significant amount of weight could greatly reduce the incidence of these diseases.

“Knowing what celastrol does at the molecular level could help drug developers make safer obesity treatments,” explains Zhang. “Celastrol is too toxic to use as an obesity drug, and we’re working on modifying it to make it more tolerable, but it may also help to find other molecules that work the same way.”

“Our findings suggest that Nur77 could be a drug target for future anti-obesity drugs,” adds Zhang. “Other studies have also indicated that this receptor has an important role in regulating metabolism.

More than one-third of the U.S. adult population, or 74 million people, are obese, putting them at greater risk for type 2 diabetes, heart disease, fatty liver disease, arthritis of the knees and certain cancers. Finding treatments that help

Zhang and his lab have identified celastrol’s target, a receptor called Nur77. Their research, published recently in Molecular Cell, shows that celastrol prevents weight gain in mice fed a high-fat diet by altering the function of Nur77.

“Now we want to figure out how celastrol’s effects on mitochondria relate to metabolism.

Celastrol seems to make cells more sensitive to leptin, a hormone that inhibits hunger, so we plan to look for connections between Nur77 and leptin signaling in the appetite center of the brain.”

38

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SUMMER 2017

DISCOVERY HUB

39

DISCOVERY HUB

Xiao-Kun Zhang, Ph.D., adjunct professor in the Tumor Initiation and Maintenance Program Malene Hansen, Ph.D., professor in the Development, Aging and Regeneration Program

What Doesn’t Kill You Makes You Stronger Just about everyone knows that a little stress early in life makes you better able to handle similar challenges later, and biologists have found the same to be true for simple organisms and human cells. New findings from the lab of Malene Hansen, Ph.D., identify the cellular process that’s crucial to these benefits—one that’s also key for a long lifespan.

That process is autophagy, a means of recycling cells’ broken or unneeded parts to build new machinery and generate energy. Autophagy has been linked to longevity, in no small part because of research by Hansen’s group.

“We used C. elegans—tiny roundworms—to test the importance of autophagy in becoming stress resistant,” says Caroline Kumsta, Ph.D., staff scientist in Hansen’s lab and lead author of the study, published in Nature Communications.

C. elegans, 1 mm-long roundworms used to study aging

Kumsta and colleagues found that exposing worms to heat for one hour increased autophagy rates throughout the worms’ tissues. Heat treatment made normal worms better able to survive a longer incubation at the same temperatures a few days later, while worms deficient in autophagy failed to benefit.

The researchers reasoned that mild heat stress might improve the worms’ ability to handle another condition that worsens with

The average lifespan in the U.S. has increased from about 66 years in 1965 to about

76

years today Source: Centers for Disease Control

age—buildup of aggregated proteins, which damages cells. Exposing worms that make sticky proteins, similar to those that cause Huntington’s disease, to a mild heat shock reduced the number of protein aggregates.

In Huntington’s, protein clumping causes massive brain degeneration, which is eventually fatal.

“Our finding that brief heat exposure helps alleviate protein aggregation could lead to new approaches to slow the advance of neurodegenerative diseases,” says Hansen.

“A lot of people ask if this means they should go to the sauna or do hot yoga,” jokes Kumsta.

“That may not be a bad idea. But we have a lot more research to do to figure out whether that has anything to do with induction of autophagy by heat stress.”

New Research Explains How This Experimental Herb-derived Obesity Drug Works When a recent study identified a chemical found in an herb used in traditional Chinese medicine as a potential treatment for obesity, it made headlines. That’s because there are not yet any good ways to help obese people lose weight—the drugs that are available now work no better than diet and exercise, on average leading to a loss of only 5 percent of a person’s weight.

2.8 At least

million people die each year as a result of being overweight or obese.

Source: World Health Organization

Celastrol is a chemical compound isolated from the root extracts of the Thunder God Vine.

However, that study was only a first step— the molecular basis for the effects of the compound, called celastrol, was unknown. New research from the lab of Xiao-Kun Zhang, Ph.D., adjunct professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), identifies the receptor on which celastrol acts, and the cellular processes it alters.

people lose a significant amount of weight could greatly reduce the incidence of these diseases.

“Knowing what celastrol does at the molecular level could help drug developers make safer obesity treatments,” explains Zhang. “Celastrol is too toxic to use as an obesity drug, and we’re working on modifying it to make it more tolerable, but it may also help to find other molecules that work the same way.”

“Our findings suggest that Nur77 could be a drug target for future anti-obesity drugs,” adds Zhang. “Other studies have also indicated that this receptor has an important role in regulating metabolism.

More than one-third of the U.S. adult population, or 74 million people, are obese, putting them at greater risk for type 2 diabetes, heart disease, fatty liver disease, arthritis of the knees and certain cancers. Finding treatments that help

Zhang and his lab have identified celastrol’s target, a receptor called Nur77. Their research, published recently in Molecular Cell, shows that celastrol prevents weight gain in mice fed a high-fat diet by altering the function of Nur77.

“Now we want to figure out how celastrol’s effects on mitochondria relate to metabolism.

Celastrol seems to make cells more sensitive to leptin, a hormone that inhibits hunger, so we plan to look for connections between Nur77 and leptin signaling in the appetite center of the brain.”

40

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SUMMER 2017

“We thank our donors and volunteers for their generous contribution to our Institute over the years.

Their continued support will help to ensure the future of medical discovery.”

Kristiina Vuori, M.D., Ph.D., President

OUR MISSION Sanford Burnham Prebys Medical Discovery Institute (SBP) conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. We educate the next generation of scientists to continue our work on improving human health.

WHO WE ARE • SBP pursues groundbreaking biological research and advances discoveries with the greatest potential to profoundly impact human health.

• SBP has a clear line of sight into the most pressing unmet needs of patients–knowledge that shapes research from its earliest stages and bridges discoveries from the “bench-to-bedside.”

• Powered by an entrepreneurial spirit and productive collaborations with patient advocacy groups, medical centers and drug companies, and a team of world-renowned scientists, SBP helps to bring forth innovative treatments for cancer, neurodegeneration, immune disorders and rare diseases.

SBP conducts biomedical research funded primarily by grants from agencies of the federal government and private philanthropic support.

SBP is a California not-for-profit public benefit corporation under Section 501 © (3) of the Internal Revenue Code.

Trustees

FOUNDERS Dr. William H. and Lillian Fishman* HONORARY TRUSTEES

Roberta and Malin Burnham Joseph C. Lewis T. Denny Sanford TRUSTEES AND OFFICERS

Henry L. Nordhoff CHAIRMAN

James C. Blair, Ph.D. VICE CHAIRMAN

Perry Nisen, M.D., Ph.D. CHIEF EXECUTIVE OFFICER DONALD BREN CHIEF EXECUTIVE CHAIR

Kristiina Vuori, M.D., Ph.D. PRESIDENT PROFESSOR, NCI-DESIGNATED CANCER CENTER PAULINE AND STANLEY FOSTER PRESIDENTIAL CHAIR

Gary Chessum, ACMA, CGMA CHIEF FINANCIAL OFFICER

Knox Bell CORPORATE SECRETARY

Lorenzo M. Berho David W. Down Daniel J. Epstein M. Wainwright Fishburn, Jr. Carol G. Gallagher, Pharm.D. William Gerhart Alan A. Gleicher James E Jardon II Donald L. Jernigan, Ph.D. Gregory T. Lucier James Myers Douglas H. Obenshain Donald J. Rosenberg, J.D. Edward R. Schulak Kazumi Shiosaki, Ph.D. Stuart A. Tanz Luder G. Whitlock Jr.

*Deceased

Stay informed about our discoveries at SBPdiscovery.org The research at Sanford Burnham Prebys Medical Discovery Institute is made possible in part by philanthropic support. For more information, please contact giving@SBPdiscovery.org or 1-877-454-5702.

10901 North Torrey Pines Road La Jolla, California 92037

SBPdiscovery.org

41

40

PATHWAYS

SUMMER 2017

“We thank our donors and volunteers for their generous contribution to our Institute over the years.

Their continued support will help to ensure the future of medical discovery.”

Kristiina Vuori, M.D., Ph.D., President

OUR MISSION Sanford Burnham Prebys Medical Discovery Institute (SBP) conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. We educate the next generation of scientists to continue our work on improving human health.

WHO WE ARE • SBP pursues groundbreaking biological research and advances discoveries with the greatest potential to profoundly impact human health.

• SBP has a clear line of sight into the most pressing unmet needs of patients–knowledge that shapes research from its earliest stages and bridges discoveries from the “bench-to-bedside.”

• Powered by an entrepreneurial spirit and productive collaborations with patient advocacy groups, medical centers and drug companies, and a team of world-renowned scientists, SBP helps to bring forth innovative treatments for cancer, neurodegeneration, immune disorders and rare diseases.

SBP conducts biomedical research funded primarily by grants from agencies of the federal government and private philanthropic support.

SBP is a California not-for-profit public benefit corporation under Section 501 © (3) of the Internal Revenue Code.

Trustees

FOUNDERS Dr. William H. and Lillian Fishman* HONORARY TRUSTEES

Roberta and Malin Burnham Joseph C. Lewis T. Denny Sanford TRUSTEES AND OFFICERS

Henry L. Nordhoff CHAIRMAN

James C. Blair, Ph.D. VICE CHAIRMAN

Perry Nisen, M.D., Ph.D. CHIEF EXECUTIVE OFFICER DONALD BREN CHIEF EXECUTIVE CHAIR

Kristiina Vuori, M.D., Ph.D. PRESIDENT PROFESSOR, NCI-DESIGNATED CANCER CENTER PAULINE AND STANLEY FOSTER PRESIDENTIAL CHAIR

Gary Chessum, ACMA, CGMA CHIEF FINANCIAL OFFICER

Knox Bell CORPORATE SECRETARY

Lorenzo M. Berho David W. Down Daniel J. Epstein M. Wainwright Fishburn, Jr. Carol G. Gallagher, Pharm.D. William Gerhart Alan A. Gleicher James E Jardon II Donald L. Jernigan, Ph.D. Gregory T. Lucier James Myers Douglas H. Obenshain Donald J. Rosenberg, J.D. Edward R. Schulak Kazumi Shiosaki, Ph.D. Stuart A. Tanz Luder G. Whitlock Jr.

*Deceased

Stay informed about our discoveries at SBPdiscovery.org The research at Sanford Burnham Prebys Medical Discovery Institute is made possible in part by philanthropic support. For more information, please contact giving@SBPdiscovery.org or 1-877-454-5702.

10901 North Torrey Pines Road La Jolla, California 92037

SBPdiscovery.org

41

NONPROFIT ORGANIZATION US POSTAGE

PAID

SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

A SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE PUBLICATION | NEUROSCIENCE ISSUE | SUMMER 2017

10901 North Torrey Pines Road La Jolla, California 92037 SBPdiscovery.org

BRAIN Rethinking diseases of the mind

Our work is made possible through the generous donations of people like you.

If you wish to support our research, please email giving@SBPdiscovery.org or call 1-877-454-5702.