Not just women, but one man after another has come to our institute, telling us that it was time for men to step up and take responsibility for birth control.
Here at the Lundquist, our researchers have been ahead of the curve and running clinical trials with NIH sponsorship on various male birth control methods including contraceptive gels, oral pills, and long-term injectables.
So far, these trials have shown that a totally reversible inhibition of sperm production could be successful, without showing any change in mood or sexual function.
Once FDA approved and on the market, we already know that more than 40% of unplanned pregnancies would be avoided with better and more effective male contraception options.
The Lundquist Institute is celebrating its 70th anniversary this year. One of our hallmarks during the last 70 years is knowing that our award-winning researchers work every day at the cutting edge of scientific discovery.
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In this issue, Meet the Board introduces Paul Kuc, multilingual world traveler, financial wizard with freedom as his raison d’être 10 MEET OUR SCIENTISTS
This issue we profile Dr. Denise Al Alam and Dr. Soula Danopoulos who study the molecular and cellular aspects of lung development, especially as it affects premature infants with Down Syndrome.
Dr. Matt Budoff explains why our hearts need a mammogram.
Dr. Anita Nelson is one of the legends extraordinaire at the Lundquist, and we look at her amazing career.
We present some of the latest news highlights from our Investigators.
In this issue’s column, Dr. Eiji Yoshihara examines stem cell therapy for diabetes.
The Institute has launched an exciting new program that introduces elementary public school students to science.
“In today’s scientific landscape, TLI is a unique institution. We not only conduct groundbreaking research, but we also take that research and develop new therapies... We are a fullcycle bioscience hub that starts at the bedside then goes to the bench and beyond, often launching startups that lead to full-fledged businesses that circle back to the bedside.”
It is an honor for me to serve as the Chair of The Lundquist Institute (TLI) Board of Directors. I come to this role and its responsibilities with a combination of awe and anticipation. I am in awe because of all the great work that has been accom plished by the Institute. After all, 2022 marks our 70th year conducting innova tive research that helps save and improve lives. And I feel anticipation because there are still many, many more remarkable sci entific breakthroughs to come.
For me, the Institute is a beacon of sci ence. We started our 70th year by having a float in the Rose Parade and I am struck by what Dr. Emil Kakkis, one of our Legends and a sponsor of the float, said after he rode in the parade: “It was an amazing ex perience and the crowd was enthusiastic and they were calling out, ‘Science, Sci ence!’ They got what we’re about.”
It’s true. Science is at the core of so much human progress. We see this throughout history and especially in the last 100 years. Humanity moves forward due to scientific advances. There is a clear correlation between overall quality of life and science.
In today’s scientific landscape, TLI is a unique institution. We not only conduct groundbreaking research, but we also take that research and develop new therapies whether it is the enzyme replacement work done by Dr. Kakkis or the tiny new medical device developed by Dr. RueyKang Chang that is designed for screening newborns for long QT syndrome, a rare genetic disease that is a cause of sudden infant death syndrome, or SIDS. We are a full-cycle bioscience hub that starts at the bedside then goes to the bench and beyond, often launching startups that lead to full-fledged businesses that circle back to the bedside.
As Chair, my highest priority is to con tinue to strengthen the bond between TLI investigators on the board with our community board members. I want to make sure our community board members and investigator board members are in sync and build a synergistic unity. If our community board members appreciate the efforts and activities of our investigators and our investigator trustees appreciate the time, effort, and serious commitment made by our community members, the board can speak with a unified voice. To be effective, we must understand each other’s perspectives and use them to build a mutu ally trusting relationship. My predecessors made huge strides in achieving that, but we can still do more going forward.
My hope is that we energize our fund raising efforts and achieve our long-term financial goals by maximizing these chan nels of communication and using them to create philanthropic opportunities that have not yet been realized. It has been a wonderful 70-year ride, but I expect much more to come between now and our dia mond anniversary in 2027.
Finally, it is important to keep in mind that our investigators are the essence of what we do here. Without them there are no breakthroughs, no discoveries, no startups, no new therapies, nor any new medical devices.
While we endeavor to realize the phil anthropic successes that our combined ef forts promise, I urge you to read on in this issue of Reach and learn more about what we do here at The Lundquist Institute and what is on the horizon.
Mitch Sayare Chair of the Board, The Lundquist Institute
“Since 2018, we have a graduate education program leading to the PhD. Our ‘newly recruited’ have participated extensively in the TLI PhD Program in Translational Research. Fully 35 PhD student research rotations have been carried out in the labs of the recruits over the past four years, and the majority of our students are now pursuing their thesis research in one of those labs.”
As part of their pledge agreement, leading to the renaming of LA BioMed to The Lundquist Institute, our benefactors, Melanie and Richard Lundquist stipulated that their donation should be applied to the recruitment and retention of the best and the brightest. This is what we are doing, and our success in this regard can be directly traced back to this request by the Lundquists.
As you will see from this edition of Reach, our highly successful recruitment of several new investigators is starting to pay off. As you may recall, in 2020, in the height of the nascent COVID-19 outbreak, seven new investigators were recruited and transitioned to the Lundquist Insti tute (TLI). Six of the seven were what we refer to as “early-career.” To date, and some two years after their arrival, they are bringing in the extramural funding need ed to continue TLI’s 70-year tradition of biomedical innovation.
In ice hockey or soccer, scoring de pends on the number of “shots on goal”. Same with research funding. Very often, getting that proposal funded depends on a number of factors. These could include the number of competitors in the same field who are applying at the same time, the amount of funds available and the consequent pay-lines, or even who exactly has reviewed one’s proposal; friend or foe. And so, taking all of this into account, the number of shots on goal, or the number of proposals submitted must be great. And indeed, it was. Since their arrival, such a short time ago, this cadre of “newbies” has submitted 88 proposals to numerous sources, but predominantly federal ones, in support of their research. Shots on goal.
Since 2018, we have a graduate edu cation program leading to the PhD. Our “newly recruited” have participated extensively in the TLI PhD Program in Translational Research. Fully 35 PhD student research rotations have been car ried out in the labs of the recruits over the past four years, and the majority of our students are now pursuing their thesis re search in one of those labs.
And they teach. We have an extensive curriculum for our PhD students and many of our Early-careers spend time lec turing or serving as preceptors in courses devoted to TLI’s translational research. And now, with our High School Summer Fellowship Program in its 44th year, they are involved not only in the didactic part of the program, but in the hands-on lab experience as well.
And so, my friends, the good news is that in the last two years, the average age of our investigators has dropped pre cipitously. Yes, in part because we have a number of senior investigators who have retired from clinical duties, and are, thankfully, continuing their highly successful, and well-funded research projects, but also because of a highly successful recruitment effort by TLI for a youthful, energetic and successful cadre of investigators.
David Meyer President and CEO
Our highly successful recruitment of several new investigators is starting to pay off. As you may recall, in 2020, in the height of the nascent COVID-19 outbreak, seven new investigators were recruited and transitioned to TLI. To date, and some two years after their arrival, they are bringing in the extramural funding needed to continue TLI’s 70-year tradition of biomedical innovation.
“ Whether it’s being on the Institute Board or the CFO of a cutting-edge company, being challenged and keeping your options open is about freedom. That’s my reason for living and doing what I do.”
For Institute Board member Paul Kuc, freedom is his raison d’être. “I like being challenged,” he says.
“I like to always find something that would be disruptive, and that’s why I worked for companies in my career that challenged me. That’s also why I believe research is there—to disrupt and to move our science forward. Whether it’s being on the Insti tute Board or the CFO of a cutting-edge company, being challenged and keeping your options open is about freedom. That’s my reason for living and doing what I do.”
As a member of the Lundquist Board of Directors since 2021, Kuc brings a breadth of international experience and unique financial expertise to the role. Born and raised in Poland, he attended the Uni versity of Lodz School of Economics and spent time as an exchange student, first in Spain and later in Holland. He is fluent in four languages, Polish, Spanish, English, and Portuguese.
Upon receiving a master’s degree in economics, Kuc returned to the northwest province of Asturias in Spain, eventual ly forming a marketing company with friends from his foreign exchange years.
“It was a data capturing company,” ex plains Kuc. “That was quite innovative at the time. Now, it’s very common to use big data and computers. At the time, especial ly in Spain, that wasn’t very common.”
After spending a few years in Asturias and marrying a woman from his native country, Kuc’s next move was to Toronto, Canada. He and his new wife were inter ested in finance and economics, so they decided to attend the Ivey Business School at the University of Western Ontario— long ranked as the number one business school in Canada—to earn MBAs.
As Kuc recalls, “Most of my peers from University of Western Ontario went to work for financial institutions, including my wife. We started together, and ever since, she has worked for either banks, or financial advisors, or portfolio managers, and so on. So, I was one of those who went to a more corporate career. After gradua tion, I joined the Eli Lilly company.”
While at Eli Lilly, he was a financial analyst for big project on antidepressants. Next, he went to work for Monsanto, which, at the time, was shifting from being a chemical company to becoming a plantbased biotech company.
With Spanish under his belt, Monsanto sent him to Argentina where he spent four years as a lead financial analyst for a venture with an agricultural focus. Kuc
explains his professional journey from that point. “I decided to move on from Monsanto to help with climate change and how people live their lives. I joined a company called Ceres Bioscience, whose purpose was to replace fossil fuels with biofuels.”
In 2016, Kuc was approached by the Institute, then known as LA BioMed, to serve as chief financial officer (CFO). As Kuc tells it, “I was quite excited about the story of an incubator that was already ger minating, I think, in Dr. Meyer’s head. It was before the Lundquist donation, but it was in a time where there was already talk about the new Medical Research Labora tory building. So, when I joined, one of the challenges was to build that new research center, to have several companies join, and to develop a platform where we could sell our rights to some of our inventions in exchange for royalties. It was a very inter esting proposition.”
In the end, Kuc spent only one year at the Institute. In 2017, he was approached by a company in Santa Monica built on an intriguing concept. In his own words, “I really couldn’t resist that temptation to be come a CFO for a company called Provivi. It was founded by only the fifth woman to get the Nobel Prize in Chemistry, Frances Arnold from Caltech, and based on the science of using insect pheromones for pest control in crops.”
But Kuc did not take his decision to leave the Institute lightly and was happy to stay involved in various ways, including as a member of its Board. “I really love the Institute and wanted to maintain a very good relationship as a frequent visitor to all the events and was later invited to become a chair of the Audit Committee, which is something quite rewarding, and then a member of the board in 2021,” he
says. “Being part of the Institute board is quite an honor,” he continues. “We take certain things for granted here in the States, but I have seen real inequality in places like Brazil and Argentina. What I like about the Institute is it helps under served populations in the area around Torrance and beyond. The diseases that they are trying to solve is, sometimes as we know, for a very small niche of society, and it’s very novel to do that. So, I’m very happy about. It’s quite rewarding.” Ever the explorer of new professional opportunities and adventures, Kuc left Provivi earlier this year. He is now part of a company called Sensei Ag, an agricul tural company focusing on cutting-edge technologies related to growing food indoors and improving the environment and human nutrition at the same time. Kuc joined as CFO and is quite excited about
“I was quite excited about the story of an incubator that was already germi nating, I think, in Dr. Meyer’s head. It was before the Lundquist donation, but it was in a time where there was already talk about the new Medical Research Laboratory building. So, one of the challenges when I joined was to build that new research center, to have several companies join, and to develop a platform where we could sell our rights to some of our inventions in exchange for royalties. It was a very interesting proposition.”
the future expansion of these greenhouses. Kuc explains that many factors help make Sensei a company of the moment and relate to his being on the Institute Board. “I really hope that my new company can make a positive difference in agriculture,” he says, “Just as I know that the Lundquist Institute is making a real difference every day in the world of biomedical research.”●
The Lundquist Institute’s longtime focus on researching and treating respiratory diseases gains a boost in funding
here is a saying among lung health advocates that “if you can’t breathe, nothing else matters.” This adage rings particularly true for people with chronic obstructive pulmonary disease, or COPD, as every breath can feel like a struggle for life. COPD is a group of diseases—including chronic bronchitis and emphysema—that cause breathing-related problems like frequent coughing, excess phlegm, and shortness of breath.
“COPD research is chronically underfundeD. It’s the third or fourth leading cause of death in the United States, yet it’s way, way down on the funding list of chronic diseaseS or medical conditIons. And it’s a very deserving patient population that, frankly, has been very long ignored.”
– Richard CasAbuRi, PhD, MD
“by supPorting us, PeRF is also reaching diverse populations and bringing research to those indivIduals who traditIonally don’t have goOd acCesS to it.”
– HarRy RosSiter, PhDThanks to a new infusion of resources, The Lundquist Insti tute (TLI) will now be able to dedicate more time and money to COPD research and patient care. The Pulmonary Education and Research Foundation (PERF), a not-for-profit organization cre ated in 1984, and based in the South Bay area like TLI, recently donated more than $700,000 to the “Pulmonary and Exercise Research Fund” at TLI to support investigators and trainees to continue this important work. According to TLI investigator, Richard Casaburi, PhD, MD, “Their mission is to promote pul monary rehabilitation as a therapy, and we’ve had a very close interaction over the years, doing many projects together.” Dr Casaburi has served as President of the PERF Board of Directors for 29 years, and adds, “It’s had the reputation of being a small foundation that accomplished big things, sort of the little engine that could.”
Over the years, PERF has funded a series of pilot projects that have later served as an entrée to larger grants. In fact, PERF board members—including Dr. Casaburi and other TLI investi gators—have published over 700 research articles in the fields of pulmonary medicine and exercise sciences.
At TLI, researchers have been investigating COPD for more than 35 years to help the more than 16 million Americans who suffer from the disease. But COPD research is chronically under funded. It’s the third or fourth leading cause of death in the Unit ed States, yet it’s way, way down on the funding list of chronic diseases or medical conditions.
At TLI, PERF funds will go to its Institute of Respiratory Medi cine and Exercise Physiology, a world-leading venue for respira tory medicine research spanning basic and clinical science. This
Institute-within-the-Institute at TLI aims to identify mechanisms, develop diagnostic tools, and test treatments for respiratory dis ease by nurturing and promoting research activities in the fields of physiology and medicine that involve the lungs, heart, blood, muscles, and the immune and nervous systems.PERF has also funded a sizable research registry at the Institute that currently has over 400 members, which will continue once the PERF tran sition is complete. According to TLI Investigator Harry Rossiter, PhD, “You go to any of the big research powerhouses in this area, and you’ll find a very one-color, one-dimensional type of partici pant. We are proud to have good representation from our African American and Hispanic community members who regularly participate in our research studies. So, by supporting us, PERF is also reaching diverse populations and bringing research to those individuals who traditionally don’t have good access to it.”
In addition to the infusion of funding from PERF, Dr. Rossiter recently received a grant of $112,000 from the Johnny Carson Foundation, which will support the training of the next genera tion of COPD researchers. “This grant will go toward our unique research training program that brings together basic, transla tional, and clinical researchers, devoted to the understanding of physiological impacts of chronic respiratory disorders on respi ratory and physical function and to translate this knowledge into therapeutic strategies,” says Dr. Rossiter. “Our research efforts are embedded alongside the County Hospital system, focusing on patients from diverse and underserved backgrounds. This new support will build on our 30 years of research success to identify new COPD therapeutics, and our excellent track record in train ing the next generation of COPD researchers. We are also pleased to be addressing COPD, the very disease that Johnny Carson suf fered from in his life.” ●
In the late 1970s, Mary Grancell, who suffered with COPD, was treated in the Pulmonary Rehabilitation Program at the Little Company of Mary Hospital in Tor rance, California. Mary Burns, RN was the program leader. Seven years later, the special care she gave would be the catalyst that launched the Pulmonary Education and Research Foundation (PERF) with a gift from Mary’s widower, Alvin Grancell.
With Mr. Grancell as its vice president and key donor, and Ms. Burns as its executive vice president, PERF grew from a two-per son operation to a leading funder of chronic obstructive pulmonary disease (COPD) research and patient education efforts. At 93 years old, Ms. Burns still serves as exec utive vice president.
After earning her RN degree from the Hartford Hospital School of Nursing in Connecticut, Ms. Burns was a staff nurse at the Little Company of Mary Hospital. In 1976, she founded the Pulmonary Rehabili tation Program. The discipline of pulmonary rehabilitation had only been recently estab lished and Ms. Burns reveled in innovating. Ocean cruises for COPD patients and annual Respiratory Rallies were only two of her many inventions. She’s been a leader in the development of the field of rehabil itative sciences and the recipient of many awards for her work in pulmonary rehabili tation, including the California Medal of the American Lung Association of California in 2001 for her outstanding contributions to the field of pulmonary medicine.
As an advocate for those with COPD, Ms. Burns is also known for her work in breathing training and long-term oxygen therapy. She has even participated in research herself. As a former smoker of 20 years, Ms. Burns was the first local resident to sign up for a large-scale NIH-sponsored study at TLI in 2008 that investigated why some heavy smokers end up with COPD and others do not.
“She’s always been the spark for this organization over the years,” says Richard Casaburi, PhD, MD, president of PERF for the past 29 years and Co-Director of the Institute of Respiratory Medicine and Exer cise Physiology at TLI. ●
Mary Burns, RN has been a leader in the development of the field of rehabilitative sciences and the recipient of many awards for her work in pulmonary rehabilitation, including the California Medal of the American Lung Association of California in 2001 for her outstanding contributions to the field of pulmonary medicine.
Learn more about how PERF is helping people with COPD perf2ndwind.org
Researchers across North America were invited to submit images and video from biological samples images with MACS Imaging and Microscopy systems. This image by Dr. Soula Danopoulos taken in Dr. Denise Al Alam’s lab was the Grand Prize Winner from Miltenyi Biotech in its North America Micrcoscopy Award Competition.
Light sheet microscopy enables comparative analysis of branching morphogenesis in the intact developing human lung. At 11 weeks of development, an intact human fetal lung was immunolabeled with antibodies against SOX9 (cyan, distal progenitor cells) and ACTA2 (red, smooth muscle cells). The sample was then cleared in BABB and imaged with an UltraMicroscope II with Zoom configuration, using 90 tiles at 12.6x total magnification. The images were stitched and processed with ImageJ and Arivis software. (Imaged at the Children’s Hospital of Los Angeles Cellular Imaging Core.)
Meet Our Scientists is a feature that introduces our readers to Lundquist scientists who are making a difference in their field.
oula Danopoulos was a graduate student in Molecular and Experimental Pathology at the University of South ern California (USC) when she first met Denise Al Alam, PhD, then a postdoctoral fellow. As researchers in the laboratory of Saverio Bellusci, PhD, at Children’s Hos pital Los Angeles (CHLA), the two women shared an interest in lung development and pediatric care. As their careers progressed, so did their partnership.
Now, Danopoulos and Al Alam work together as inves tigators at The Lundquist Institute (TLI). The two have been recognized for their work. Al Alam arrived in 2020 with NIH funding in tow. Danopoulos is the recipient of the prestigious Parker B. Francis Fellowship and received a Research Project Grant (R01) grant from the National Heart, Lung, and Blood Institute at the National Institutes of Health. In recognition for her mentorship and numerous scientific contributions, Dr. Al Alam recently won the American Thoracic Society’s Assembly on Pediatrics Mid-Career Outstanding Contributions Award.
According to Dr. Danopoulos, “Both scientifically and professionally, Denise has proven to be an exceptional mentor to me. We work very well together and comple ment one another, and as a result, we have established a powerful and fruitful part nership. Peers in the scientific community view us as a team and are often inspired by the partnership we have created. In general, women in science face many obsta cles and hurdles, and such partnerships may help overcome many of these hurdles and allow for success and advancement of both careers.”
Their research has and continues to focus on human lung development and pe diatric lung diseases. They are interested in understanding the processes that take place during normal prenatal lung development, which then provides them with better insights into understanding how and why certain congenital anomalies arise, such as pulmonary hypoplasia, bronchopulmonary dysplasia, and the several com plications observed in the lungs of individuals with Down Syndrome (Trisomy 21).
Through their studies, the two researchers have built a solid foundation on under standing the molecular and cellular aspects as well as the interactions between dif ferent cell types in the lung that are important for normal human lung development.
Dr. Al Alam’s passion and commitment for lung research started during her PhD studies where she had the opportunity to interact with pediatric patients with cystic fibrosis.” She says, “I was fascinated by the complexity of the lung and touched by the resilience of these young patients, which steered my commitment toward lung diseases. It was only after my twins were born prema turely, that my interest for human lung development, prematuri ty, and congenital lung diseases took on a whole new dimension.”
Al Alam’s group was among the first to demonstrate how lung development in humans differs significantly, at the molecular level, from what has been reported in mice, highlighting the need to complement animal studies with research on human cells and tissues. “If we don’t know how it works, we won’t know how to fix it,” says Al Alam, pointing to the importance of understanding human lung development to be able to design therapies.
Dr. Danopoulos calls herself a puzzle solver. She likes to learn about things in detail and understand the mechanics behind how something—like a lung—operates. “This made research a natural fit for me,” she says.
With Al Alam, Danopoulos’s early work focused on studying lung branching morphogenesis—the process by which the tubular structures that make up most of a lung’s architecture and cellular organization are formed—in both mouse models and humans.
She elaborates on this: “Being that the lungs are one of the last organs to fully mature, complications with breathing are one of the primary sources of neonatal intensive care unit (NICU) ad missions. Therefore, I knew that I wanted to focus my research on
lung development to help provide insight for possible therapeutic targets to these babies.”
Using a macro to micro holistic approach, Al Alam and Danopou los look forward to expanding their work on trisomy 21 lung de velopment at TLI. Typically, their studies start off with a whole tissue sample to assess whether there are any structural issues using a simple staining process to identify different cell and tissue types. Then they drill down to analyze the tissue at the cellular and molecular level.
To complete their research, Dr. Danopoulos and Dr. Al Alam utilize new approaches including the ex vivo human lung explant culture, state of the art 3D imaging to assess protein localization and gene expression in lung tissues, and single cell RNA sequenc ing-based molecular analysis of multiple human lung cell lineag es. They have recently expanded on these techniques and are also using induced pluripotent stem cells for several mechanistic and lineage specific studies. Each of these methods allow them to vi sualize the tissue or cells in a living environment.
They are also able to treat the different cultures with different inhibitors or activators and assess in real-time how these treatments affect the cultures. “The translational edge of TLI is what initially drew me here as our work focuses on human translational research,” adds Dr. Al Alam. “In addition, the environment at TLI seems ideal to get our team and our research to the next level.”
●
“TLI provided both of us the opportunity and support to grow as individuals while still being able to work together as a team.”
– Dr. Soula Danopoulos
blockages required the insertion of catheters. These procedures, known as invasive angiography or cardiac catheterization, came with associated risks and very high costs upwards of $10,000. Furthermore, well over 50% of these invasive tests do not result in additional action, like a stent or bypass, and a small number result in harmful side effects, including heart attacks, infec tions, and blood vessel injuries.
At The Lundquist Institute (TLI), we have decades of experience in developing and validating a noninvasive artery imaging test using computed tomography (CT) known as a coronary CT angiogram. It is now widely available through most insurance companies and affords a 20-fold lower cost and a safer method (with 1/10th the radiation exposure and mini mal risk) than more invasive tests to assess the coronary arteries.
In addition, coronary CT angio grams perform with at least 95% accuracy when compared to tra ditional, invasive angiograms.
These scans represent two im portant advances for patients and their physicians. First, the coronary CT angiogram is the most accurate noninva sive method to detect blockages in the coro nary arteries. It is much more accurate than widely used nuclear scans, requiring 16-fold higher radiation doses, at higher costs and with lower accuracy. The newest guidelines from the American Heart Association, published in 2021, now strongly advocate for coronary CT angiograms over nuclear scans for patients.
But the second advance is even more compelling. Most heart attacks are caused by a 30% blockage that brakes and abruptly blocks blood flow. But nuclear scans and other noninvasive tests only detect severe blockages and are considered normal if there are mild blockages present. The CT angiogram can detect a blockage down to 10% irregularities in the blood vessel, allowing doctors and patients the opportunity to change
strategy to prevent buildup in the arteries and hopefully avoid any heart attack or stroke.
If we find these mild blockages, the treatments may be as simple as one’s ABCs: A = aspirin (low dose, 81 milligrams a day); B = blood pressure control (try to get blood pressure to 120/80 or better); C = cholesterol treatment; D = diet (such as the Mediterranean diet, which is very effective in preventing heart disease); and, E = exercise (most effective, but many of us need some impetus to get to our goals).
Bruce Brundage, MD, a pioneer of this modality, and the one who brought this technology to TLI back in 1991, called this coronary CT angiogram the “Mammogram of the Heart.” While we don’t quite yet have a Star Trek “medical tricorder” device that we can wave over you and detect all ailments, the coronary CT angiogram makes diagnosing heart disease much less invasive and much easier and safer than before while we continue to seek out approaches to better the test and apply it in innovative and novel ways to improve heart health. ●
“At Lundquist, we have decades of experience in developing and validating a noninvasive artery imaging test using computed tomography (CT) known as a coronary CT angiogram.”
or nearly 40 years, obstetrician and gynecologist Anita Nelson, MD, has been a fierce advocate for women’s health, directing essential family planning clinics, per forming innovative research and patient care, and teaching the next generation of nurse practitioners and OBGYN residents.
But medicine was not her initial career path. Nelson’s first de gree was a BA in economics from Occidental College, after which she spent seven years with the US Army Corps of Engineers doing economic analyses of harbors, dams, and flood control projects.
Toward the end of her time with the US Army Corps, Dr. Nel son became interested in medicine through volunteer work and started taking classes at UC Irvine toward a second bachelor’s— this time in Biology. One year after leaving the field of economics, she was on her way to earning an MD from UCLA, during which time she did rotations at Harbor-UCLA Medical Center. “I fell in love with it,” she says. “I rated Harbor as my first choice for resi dency and was lucky enough to get chosen.”
Toward the end of her residency in 1985, which ran from 1981 to 1986, she was offered the opportunity to oversee the Wom en’s Health Care Nurse Practitioner Education Programs at LA BioMed, now known as The Lundquist Institute (TLI). “It was a really unique position because it was in many ways a direct part nership between the Institute and Los Angeles County, which had established a training program for nurse practitioners from 17 Western states and Micronesia,” says Dr. Nelson, who was medi cal director of the program from 1985 to 2013. “We had graduates
from the Bering Straits, from the inner cities of Los Angeles, from North Dakota, the rural areas of Oregon, from Samoa and Guam and just all kinds of areas where they were able to bring services to women who otherwise wouldn’t get them.”
But running the Nurse Practitioner pro gram wasn’t the only position she added to her resume in 1985. All while finishing out her residency, she became the medical di rector of the Women’s Health Care Clinic in building N-28 on the Institute campus, a member of the Division of Gynecolo gy at Harbor-UCLA Medical Center, an assistant professor in the Department of Obstetrics and Gynecology at the UCLA School of Medicine, and Medical Direc tor for the Women, Infants and Children (WIC) Program for the southern part of Los Angeles County.
“I inherited this really rich system and was able to, in conjunction with the res idency that was ongoing and all the care that was going on at the hospital, really make new innovations,” says Dr. Nelson, of the collaborative care network she and
“ We had graduates from the Bering Straits, from the inner cities of Los Angeles, from North Dakota, the rural areas of Oregon, from Samoa and Guam and just all kinds of areas where they were able to bring services to women who otherwise wouldn’t get them.”
her colleagues were able to build between the Nurse Practitioner program, the women’s health clinic, the WIC program, and TLI. “We were able to transform the clinic into a very productive site for research because we were seeing so many patients and many of them were excited to be involved in the development of new contraceptive options or new ways of providing care.”
Nelson says she and her colleagues tested, at the Institute, just about every new birth control product that came out for ten years, including, in recent years, male contraceptive implants. In the late nineties, Nelson was part of a study examining whether a woman needed a pap smear, a full physical examination, STD tests, and a breast exam just to get a prescription for birth control pills. “Our clinic was very vigorous in studying this. We put our little project in the WIC center in Compton so women coming to pick up their food coupons could get started on contraception right away,” says Dr. Nelson. “The results of the study, published in the Journal of the American Medical Association, showed that women did seek other care, but they didn’t have big delays in getting their contraception by all these barriers being in the way. But I’ll tell you, it took ten years before the Centers for Disease Control adopted that as the standard of care.”
Another major study to which Nelson and TLI researchers made significant contributions was an exploration of what could be done to reduce the spread of sexually transmitted infections.
According to Nelson, the classic model was that a patient is tested, found to be positive, treated, and then a report is sent to public health officials to track down her contacts to try and treat them. The study team proposed a new model in which women who knew the partner that infected them could simply take home a prescription or even the drug to share. “If we treated her partner directly, would that reduce her chance of getting reinfected? And the answer was yes, it did,” explains Dr. Nelson. “And that’s now a CDC standard called expedited partner therapy.”
The driving force behind these research successes, and many others—Nelson has been involved in nearly 200 research projects and coauthored more than 150 peer-reviewed papers—as well as her career in general, is a deep belief in the power of education. “The investment, not only in the residents and the residency programs, but from the Institute standpoint, going into the high
schools and getting people interested in medical research is so important,” says Dr. Nelson. “We also gave continuing education to a lot of the community members. Anytime something new came out, we would teach them how to use it, or we would do continuing education courses for nurses and physicians, so we were able to really contribute in so many ways to the quality of care that women basically throughout Southern California got.”
In fact, although no longer a practicing physician or a faculty member at TLI, she is still very active in research and education and says that her time at the Institute was an absolute honor. Ever the multi-hyphenate, Nelson now serves as a volunteer teacher at USC and Children’s Hospital Los Angeles, as Medical Director of the research division at Essential Access Health, which conducts clinical trials, and as Professor and Chair of the Department of Obstetrics and Gynecology at Western University of Health Sci ences, College of Osteopathic Medicine of the Pacific.
“What I love is that, even though I’m not on faculty at Harbor, I’m able to collaborate and bring my students from Western who are interested in women’s care over to Harbor, and through the Institute they get to do research with the faculty,” says Dr. Nelson. “Paying it forward is the important thing. You’re turning out new people who have been inspired and intrigued by research. Getting them started in meaningful research and putting together this powerful package where you’ve got patients that have problems and minds in the Institute who can help solve them is just incredible.”●
“I inherited this really rich system and was able to, in conjunction with the residency that was ongoing and all the care that was going on at the hospital, really make new innovations. We were able to transform the clinic into a very productive site for research because we were seeing so many patients and many of them were excited to be involved in the development of new contraceptive options or new ways of providing care.”
The Lundquist Institute has launched an exciting new program that introduces elementary public school students to science. The new Institute initiative began offering its sciencebased curriculum to elementary school students in December of 2021 and extended its workshops through May 2022, which culminated in a graduation ceremony on May 21 of this year. Senior Vice President for Public Affairs, Jody Spillane, conceived the program’s name—Little Einsteins—as well as the educational concept behind it and is spearheading the project.
“This new endeavor brings together young grammar school students with our PhD students who will mentor them,” said Spillane. “The concept is designed to expose the students to science through a curriculum created by our grad students. Each month, the elementary school students, ages 8-10, will learn about new aspects of science from PhD students working at the cutting edge of discovery. We are very excited about this program since it now extends the Institute’s education enterprise from elementary school through Little Einsteins to our high school Summer Fellows program to our undergraduate internships, and, at the highest level, the graduate PhD program in translational research.” ●
The Little Einsteins program began in December with an introduction to the different fields of science and cell biology. In the second lesson, held in February, the focus was on human anatomy where the students learned about different organ systems in the human body and were able to work with a human torso model. The third module in March covered human embryonic development and students were able to view human model replicas. For the fourth module in April, the focus was on microbiology and how to use a microscope. The fifth and final lesson took place in May and was on chemistry and concluded with a graduation ceremony attended by Dr. David Meyer, the Institute’s President and CEO.
Abdullah Alqarihi, Ashley Barbarino (above), and Jackie Hernandez are leading the effort on the educational front.
The Lundquist Institute (TLI) has received a generous $5 million, 5-year grant from the California Institute for Regenerative Medi cine (CIRM) that will allow its PhD students, postdoctoral fellows, and clinical fellows to pursue careers in stem cell biology and regenerative medicine. This award will also support the creation of a stem-cell focused program that will enable the Institute to recruit and train researchers in stem cell research while emphasizing its translational significance, underlying ethical consider ations, and efforts to keep the community updated on the technological advances
in the field. The grant will also make it possible to retain stem cell researchers by providing access to the new and emerging companies based on TLI campus.
“This is monumental and places the Insti tute among the ranks of leading research centers for innovative stem cell research” said David Meyer, PhD, President and CEO of The Lundquist Institute. “Without a doubt, this grant means that the Institute can now recruit, train, and retain the best researchers in regenerative medicine while expanding and enhancing our already groundbreaking work in translational
research.” Jody Spillane, Administrative Director of TLI’s PhD program, added “We are thrilled to have received this distin guished award from CIRM. We are very proud that our PhD program has a very diverse graduate student cohort, 50% of whom are first-generation college students. Coupled with our existing community out reach programs, focused on translational research, including stem cell research and regenerative medicine, this award will add to the Institute’s growing impact as a research powerhouse.” ●
“ We are very proud that our program has a very diverse graduate student cohort, 50% of whom are firstgeneration college students.”
Jody SpillaneFrans Walther, MD, PhD
The Lundquist Institute’s investigator Frans Walther, MD, PhD, has received a twoyear grant from the Bill & Melinda Gates Foundation in the amount of $471,858.00 to support the development of a synthetic aerosolized lung surfactant and a non-inva
sive delivery device for use in infant respi ratory distress syndrome (RDS), a significant cause of neonatal mortality and morbidity. Newborns experiencing RDS must dramati cally increase the effort to take each breath due to lack of adequate, naturally occurring
surfactant production in their lungs. This de ficiency of lung surfactant leads to fatigue, episodes of apnea, hypoxia, wasting, and potentially death if left untreated.
The target completion date for the funded research leading to the development of an aerosolized lung surfactant is March 2024. This research is part of a multi-dimensional research project under the direction of Dr. Walther, and aimed at developing a synthetic lung surfactant to treat breathing problems in preterm infants with surfac tant-deficiency and lung immaturity and in near-term infants with surfactant inactivation due to meconium aspiration syndrome.
“I am very pleased to have received this generous grant from the Bill & Melinda Gates Foundation,” said Dr. Walther, Princi pal Investigator at The Lundquist Institute and Professor of Pediatrics at the David Geffen School of Medicine at UCLA. “This grant will allow us to test the efficacy of both liquid and dry powder surfactant formula tions along with developed delivery devices in vitro and in vivo, and to determine the best formulation of peptide, phospholipid, and excipient for lead candidate selec tion along with a device and subsequent IND-enabling studies. Our goal is to design, synthesize, and bring effective lung surfac tant peptides, modeled after the sequence of human surfactant proteins B and C to clinical care. This grant will help us achieve these research goals.” TLI CEO David Meyer, PhD, added. “This is the type of trailblazing and state-of-the-art research that we are known for, and caps off extensive innovation in the field of lung surfactants, which began at TLI as far back as the 1980s.” ●
“Our goal is to design, synthesize, and bring effective lung surfactant peptides, modeled after the sequence of human surfactant proteins B and C to clinical care. This grant will help us achieve these research goals.”
Dr. Eric Daar has received a grant from the National Institutes of Health (NIH) to study a treatment for monkeypox. The disease has been spreading throughout the world.
Dr. Daar will be testing the safety and efficacy of Tecovirimat, the currently available, but never formally studied treatment for monkeypox.
The study will enroll those with suspected or documented infection. The trial began in September 2022. ●
A major funding source is derived from the tobacco companies’ settle ments with the states, and in this case, California has created the UC-TRDRP. TLI investigators, working on various aspects of the exposure to cigarette smoke, vaping and/or nicotine have recently received major funding from this agency. TLI investigators Virender Rehan, Nick Jendzjowsky, Begoña Diaz and Lina Nih have collectively accumulated 3-year awards totaling nearly $5.5 million. ●
This highly prestigious ASM fellowship supports doctoral graduate students interested in the microbial sciences and who seek mentorship in navigating their career trajectory. Barbarino and Alqarihi were selected from a pool of thousands of applicants for this esteemed ASM Fellowship. They will be mentored for the year by seven highly accomplished mentors in various areas of microbiology.
“We at the Institute are so proud of Ashley and Abdullah,” said Jody Spillane, Sr. Vice President of Public Affairs and and Administrative Director of the PhD graduate program in translational research. “The fact that they were selected from a pool of thousands of applicants speaks to the quality of our PhD students and to their outstanding promise as future leaders in science.”
The ASM Future Leaders Mentoring Fellowship is designed to support senior undergraduate, postbaccalaureate, master’s and doctoral graduate students from underrepresented groups who demonstrate an interest in the microbial sciences and seek mentorship in navigating their careers. Microbiology sectors include, but are not limited to, academia, industry, government, nonprofit and entrepreneurship.
In the first year, mentees will be matched with a team of mentors and participate in skillset training, structured mentoring, community building and networking activities at ASM Microbe. In the second year, mentees will become peer mentors to the Annual Biomedical Research Conference for Minority Students (ABRCMS) undergraduate students in the microbiology discipline and serve as ABRCMS session moderators. In an optional third year, selected mentees will be invited to serve as an ASM mentoring ambassador to incoming cohorts and an ABRCMS judge. ●
The ASM fellowship supports doctoral graduate students interested in the microbial sciences and who seek mentorship in navigating their career trajectory.
DIABETES IS A COMPLEX DISEASE THAT affects more than 30 million people in the US alone and over 463 million people worldwide. Discovered 100 years ago, insulin has been the go-to treatment for di abetes to maintain blood sugar levels. Pro duced from pancreatic islet β cells, insulin is also the most important hormone for growth and metabolic regulation in our body.
Type 1 diabetes (T1D) often begins in childhood and is a lifelong condition in which a patient’s blood sugar levels become too high due to lack of insulin. Type 2 dia betes (T2D) is caused by loss of functional β cells and often accompanied with stress in ducers such as obesity, smoking, and aging.
Unlike salamanders that have the capac ity to fully regenerate parts of their bodies, humans have very little ability to regenerate lost cells. Since injected or infused insulin is a life-saving treatment for diabetic patients, learning how to regenerate and replace pancreatic islets has become a critical issue.
In 2000, researchers demonstrated that replacing functional islets can provide full glycemic control and a functional cure for di abetes. These therapeutics, however, have several limitations. First, there is a supply issue regarding donated cadaveric human islets. Second, transplantation of islets requires a patient to take life-long toxic im mune-suppressive drugs to avoid the iden tification of them as a foreign body and their rejection by their immune system.
Instead, the generation of functional human pancreatic islets from stem cells, which can avoid attack from host immune cells, could provide an infinite source for transplantation therapy.
Human-induced pluripotent stem cells (hiPSCs) offer an infinite supply of cells due to their self-renewal and ability to differentiate into various cell types. Using state-of-the-art technologies, our team has successfully developed a new method for generating “immune evasive” functional human pancreatic islets from hiPSCs. De livering them to patients via transplantation
“Using state-of the art technologies, our team has successfully devel oped a new method for generating ‘immune evasive’ functional human pancreatic islets from hiPSCs. Delivering them to patients via trans plantation could obviate the need for life-long immunosuppression drugs or an immune-protective device to prevent autoimmune attack in people with T1D and T2D.”
could obviate the need for life-long immuno suppressive drugs or an immune-protective device to prevent autoimmune attack in people with T1D and T2D.
We designed a novel three-dimensional culture system that generates fully scalable hiPSC-derived islet-like organoids (HILOs). In addition, we engineered the molecules that induce immune tolerance in HILOs.
When these HILOs were transplanted into immuno-competent humanized mice that possess human immune sys tems, a significant reduction in transplant rejection was observed.
To further increase the efficacy and accurate control of human organ development, I am seek ing to understand the developmental pathway of how stem cells can be directed to become human islets and how they adapt in the body. Findings from recent studies in our laboratory suggest that the functional insu lin producing β cells we generated trans formed spontaneously into immune-tolerant and immune-evasive β cells, which are characterized by the sustainable expression of immune modulating surface molecules and intracellular resistance of immune stress-induced cell death. Since immune cells directly and indirectly contribute to the immune rejection of transplanted cells, un derstanding the mechanisms of how β cells undergo this transformation and acquire the function for tolerance from autoimmune re jection may be the key for successful stem cell-based therapies for diabetes.
And, since diabetes leads to many complications associated with neuropathy, kidney failure, stroke, cancer development, and Alzheimer’s disease, among others, finding better treatments for diabetes may contribute to improving lives in many other ways. ●
2022 is the 70th Anniversary of The Lundquist Institute.
Here is a sampling of what took place during these 70 years:
• The successful fertilization through artificial implantation of the ovum, which would lead to the first ovum transfer birth 20 years later.
• The first paramedic model and first nurse practitioner training program
• The test for high cholesterol that is still in use today.
• The first Thyroid Deficiency Test for newborns
• The development of Synthetic Lung Surfactants that allow newborns with underdeveloped lungs to breathe.
• The manufacture of low-cost eye drops to treat eye infections in newborns, especially effective in developing countries, saving the eyesight of hundreds of thousands.
• The creation of Enzyme Replacement Therapy to treat Hurler-Scheie Syndrome
• The invention and production of infant heart monitors to prevent SIDS, and test for congenital heart disorders in newborns
• The first treatment for sickle cell disease ever approved for children
And so much more…from groundbreaking work in developing the first male contraceptive to advances in noninvasive breast cancer detection, our trailblazing research continues.
