Methodology Newsletter - Summer 2017

METHODOLOGY The Research and Education Newsletter of Houston Methodist

Summer 2017

Department of Defense grant drives metastatic breast cancer treatment to clinical trials in record time

by Gale Smith

The Houston Methodist Research Institute received a $16 million Department of Defense (DoD) grant to accelerate a possible treatment for metastatic breast cancer. This grant is the largest the DoD has awarded for a breast cancer clinical trial. Metastases to the lungs and liver are responsible for approximately 90 percent of breast cancer deaths every year in the United States, yet there is no cure. Existing cancer drugs provide limited benefit due to their inability to overcome biological barriers in the body and reach the cancer cells in sufficient concentrations.

Mauro Ferrari, Ph.D, president and CEO of the Houston Methodist Research Institute, and Haifa Shen, M.D., Ph.D., a lead scientist within the department of nanomedicine, led teams that developed a multi-component therapeutic drug called polymeric doxorubicin (pDox), a nano-version of a standard chemotherapy drug used for decades. The grant will allow their team, along with a cancer research team led by principal investigator Jenny Chang, M.D., to fast-track the start of a clinical trial in 2018. Chang is a partnering principal investigator on the DoD grant and will lead the planned clinical trials at Houston Methodist. >> CONT. PAGE THREE

“

The biggest challenge in medical research is successfully translating a lab discovery into a viable treatment option for people. The cycle of a cure usually takes 17 years and costs billions of dollars. We’re going from drug creation to Phase I and II clinical studies in five years.

”

– Mauro

Ferrari, Ph.D. President and CEO Houston Methodist Research Institute

Contents

FROM THE PRESIDENT On the cover of this issue of Methodology is a story that outlines a journey from an “idea to an invention” that is my life’s work and the work of hundreds of researchers over the last 25 years. It began in the early 90’s, with an idea to apply nanotechnology to one of the fundamental challenges in cancer

Featured News

therapy – achieving targeted drug delivery to cancer cells. After years of

DoD grant drives metastatic breast cancer treatment to clinical trials in record time.............. 1

iterations, a team of researchers led by Haifa Shen, M.D., Ph.D. and I, have refined the approach so that it doesn’t just improve outcomes for animal models with metastatic breast cancer, it causes full and complete remission.

Research Highlights: Using drug repurposing to give an old drug a new lease on life...........4

We are now at a crossroads – we are ready to see if this will benefit people in clinical trials. Our partner

Nanoparticles protect fetus from side effects...........................................6

proven track record of bringing new treatments to the clinic. I am very honored to work with Dr. Chang

Researchers discover key to long-lasting malaria immunity............8

hope. Join us as we take the next step toward our goal - making real advances that save lives.

Gene deletion points way to flu treatment..................................... 9

Jenny C. Chang, M.D., Director of the Houston Methodist Cancer Center has the experience and a and eternally grateful to the teams of people and the funding that has fueled this journey of faith and

Mauro Ferrari, Ph.D.

Handle with care: Portable device mimics body conditions to keep donor livers alive.............................10

Ernest Cockrell, Jr. Presidential Distinguished Chair President and CEO, Houston Methodist Research Institute Director, Institute for Academic Medicine at Houston Methodist Hospital Executive Vice President, Houston Methodist

Cytotoxins make bacterial infections more deadly...................12

Senior Associate Dean and Professor of Medicine Weill Cornell Medical College, New York, NY

Education News Amgen Scholar Joy Wolfram, Ph.D.... 14 Clinical Translation Management Program goes online........................ 15

From idea to clinic

Of Interest Awards & Accolades.......................16 Greg Nelson, appointed chair of the Houston Methodist Board of Directors.............................................18

1992

Conception

of Silicon Microparticle for Cancer Therapy

2011 2008

Development Multistage Delivery System

Discovery iNPG-pDox

2013

Patent Pending iNPG-pDox for Cancer Therapy

DoD Innovator Awards

>> CONT. FROM PAGE ONE

Houston Methodist receives its largest grant in history Through an injectable nanoparticle generator (iNPG) created by the Houston Methodist team, the delivery of pDox led to never before seen results in mice models with triple negative breast cancer that had metastasized to the lungs. A March 2016 Nature Biotechnology paper showed long-term cures for triple negative breast cancer with lung and liver metastases in about 50 percent of the preclinical cases. That’s equivalent to about 24 years of long-term survival following metastatic disease for humans. At the same time, the overall survival benefit, even for mice that were not cured, was also unprecedented.

Doxorubicin has adverse side effects to the heart and is not an effective treatment against metastatic disease.

Due to the body’s own defense mechanisms, most cancer drugs are absorbed into healthy tissue causing negative side effects, and only a fraction of the administered drug actually reaches the tumor. The Houston Methodist treatment strategy would enable sequential passage of the biological barriers to transport the pDox into the heart of the cancer.

The active drug is only released inside the nucleus of the metastatic disease cell, avoiding the multidrug resistance mechanism of the cancer cells.

Ferrari, who is considered one of the founders of nanomedicine and oncophysics (physics of mass transport within a cancer lesion), has spent more than 24 years searching for a solution to effectively deliver cancer therapeutics. The timeline below illustrates his own journey as an innovator and the journey of the iNPG-pDox drug from an idea to an invention. Houston Methodist's next steps include developing good laboratory practices (GLP) for this drug prior to seeking FDA approval and the start of human clinical studies.

“ If the new drug is effective in patients, this could mean a significant

reduction in breast cancer deaths associated with lung and liver metastases, increased long-term survival, and enhanced quality of life.

– Jenny Chang, M.D. Emily Herrmann Chair in Cancer Research & Director, Houston Methodist Cancer Center

2018

2014

Patent Issued for Porous Silicon Manufacturing

2015

Preclinical Validation iNPG-pDox

2016

Clinical Trials

cGMP Manufacturing

”

2021

Goal: Drug in Clinic

iNPG-pDox

DoD Breakthrough Award National Cancer Institute - Center Grants

3

RESEARCH HIGHLIGHTS

USING DRUG REPURPOSING

TO GIVE AN OLD DRUG A NEW LEASE ON LIFE

by Patricia Akinfenwa, Maitreyi Muralidhar and Katie Wooldridge

Drug repurposing involves discovering new uses for existing drugs. The process of bringing a new drug to the clinic is long, expensive, and arduous with daunting failure rates. Using drugs that were tested previously for other indications can be an efficient way to Jenny C. Chang, M.D.

Angel A. Rodriguez, M.D.

Stephen T. Wong, Ph.D.

get new treatments to patients faster.

DRUG IN CLINIC

DISEASE

FDA Approved

Breast Cancer

CLINICAL RESEARCH

CAUSE

Gene Mutation

Phase I, II & III

DRUG REPURPOSING

PRECLINICAL RESEARCH Laboratory Testing

4

SCREENING

Drug Libraries

Jenny Chang, M.D., Emily Herrmann Chair in Cancer

L-NMMA was originally tested in thousands of patients for

Research, and her team have advanced a potential

the treatment of cardiogenic shock, where blood circulation

treatment for metaplastic breast cancer — the most

to the heart is severely restricted and the heart cannot

aggressive subtype of triple negative breast cancer

pump enough oxygenated blood to the body's organs.

(TNBC), into clinical trials in just under four years by

However, the U.S. Food and Drug Administration did not

taking advantage of drug repurposing.

grant approval of L-NMMA to treat cardiogenic shock

The first thing the team did was to analyze tumor samples from metaplastic breast cancer patients. They found the

because the drug did not meet the study objectives and endpoints for the clinical trial.

same gene mutated in 39 of the 40 tumor samples. The

In a paper published in the Journal of the National Cancer

mutation was in the gene RPL39, which like HER2 (a gene

Institute, Chang and her team report that L-NMMA, in

overexpressed in 1 out of 5 breast cancers), is considered

combination with standard chemotherapy, shrunk tumors

an oncogene. This means that cells carrying the erroneous

in mice bearing human metaplastic breast tumors.

form of this gene divide uncontrollably and result in rapid tumor growth. RPL39 regulates the expression of an enzyme called inducible nitric oxide synthase (iNOS).

Houston Methodist researchers found that patients with high expression of RPL39 and iNOS had lower overall survival. Intuitively, the team wanted to investigate the effects of iNOS inhibition on the treatment of TNBC. To identify a suitable iNOS inhibitor, Chang and her team approached Stephen Wong, Ph.D., an expert in bioinformatics.

Wong, the John S. Dunn, Sr. Presidential Distinguished Chair in Biomedical Engineering, and his team mined though digital libraries of thousands of drug compounds and their mechanisms of action, to identify one with the desirable iNOS inhibition properties — Tilarginine Acetate (L-NMMA). Research suggests that L-NMMA inhibits the body from producing iNOS, which controls the production

Encouraged by the positive preclinical data, researchers at Houston Methodist Hospital are now investigating if combining L-NMMA and standard chemotherapy is a safe treatment option for patients with locally advanced or metastatic TNBC. The primary goal of this Phase I clinical study is to better understand the maximum tolerated dose and the toxicities associated with this drug combination.

“L-NMMA combined with standard chemotherapy treatment has already proven to be an effective small molecule inhibitor in mice," said Angel Rodriguez, M.D., principal investigator of the Phase I study and director of the Triple Negative Breast Cancer Clinic at the Houston Methodist Cancer Center. "Our initial findings could lay the foundation for developing new therapies for women with triple negative breast cancer, for which prognosis is extremely poor."

of nitric oxide. The lowered nitric oxide levels reduce the creation of new tumor blood vessels which feed the cancer

Dave B, Gonzalez DD, Liu ZB, Li X, Wong H, Granados S, et. al. Role of RPL39

stem cells, preventing further tumor growth and the spread

in Metaplastic Breast Cancer. J Natl Cancer Inst. 2016 Dec 31;109(6)

of cancer cells.

“ The repurposed drug eliminated cancer in nearly all of the mice when combined with standard chemotherapy. Our goal is to turn metaplastic breast cancer from a debilitating disease into a chronic illness.

– Jenny Chang, M.D.

”

mily Herrmann Chair in Cancer Research & E Director, Houston Methodist Cancer Center

5

RESEARCH HIGHLIGHTS

Nanoparticles target therapy to mother's uterus

protecting growing babies from side effects

by Patricia Akinfenwa

Preterm birth affects one out of every 10 babies born in the U.S. every year. These premature babies miss critical development time and are at higher risk of serious physical and mental disabilities, and even death. Preterm labor can be slowed with drugs like indomethacin that act on the maternal uterus, but these drugs can leak from the maternal blood into the blood stream of the fetus and cause side effects for the developing fetus related to heart, kidney and brain disorders.

Researchers at the Houston Methodist Research Institute tackled the challenge of efficiently targeting the labor-slowing drug indomethacin to maternal uterine tissue and minimized fetal exposure and the risk of side effects. In a study published in Scientific Reports, a journal of the Nature Publishing Group, a team led by Assistant Professor of Nanomedicine Biana Godin, M.Sc. Pharm, Ph.D. created a protective nanoparticle coated with a chemical that specifically binds to oxytocin receptors in the uterus. Receptor binding is followed by targeted release of the drug into the uterus, while the nanoparticle protects other tissues from unnecessary exposure.

The Godin team showed that these nanoparticles delivered higher therapeutic levels of indomethacin to the uterus and reduced fetal exposure. In the next phase of research, the team will examine nanoparticle drug delivery in expectant

6

Oxytocin receptor

QUICK FACTS HOUSTON METHODIST

Uterus

Maternal blood supply This illustration was published in the journal Scientific Reports.

animal models that closely resemble human physiology during

8 2,165 810,880 103,783 21,195

pregnancy. If successful, this work could reduce the risks for fetuses that are associated with current treatments used to prevent preterm labor.

Research on this project was conducted in collaboration with Jerrie Refuerzo, M.D. and Monica Longo, M.D. Ph.D. from the University of Texas Health Science Center.

Our nanoparticle directly targets receptors on the uterus and allows for local drug release. This decreases chances of the drug crossing the placenta and protects the developing baby.

“

“

– Biana Godin, MScPharm, Ph.D. Assistant Professor of Nanomedicine Houston Methodist

Refuerzo JS, Leonard F, Bulayeva N, Gorenstein D, Chiossi G, Ontiveros A, Longo M, Godin B. Uterus-targeted liposomes for preterm labor management: studies in pregnant mice. Sci Rep. 2016 Oct 11;6:34710.

RESEARCH HIGHLIGHTS

Indomethacin in nanoparticle capsule

“

5,591 1,843 622 46 412 23,319 1,075

Hospitals Operating beds Outpatient visits Admissions

Employees

Physicians Credentialed researchers Faculty GME programs Trainees

(residents, postdoctoral fellows & students)

CME, GME & MITIE learners Clinical protocols

440,000

Sq.ft. dedicated research building with 12 stories and 150 lab benches

100,000

Additional sq.ft. research space embedded throughout the hospital

$49.6 M $131 M

Annual extramural funding Annual research expenditures

5

RESEARCH HIGHLIGHTS

Researchers discover

key to long-lasting

malaria immunity and

potential vaccine targets

by Patricia Akinfenwa

Houston Methodist researchers have discovered an immune protein that facilitates long-lasting immunity against malaria. In a study published in Immunity, they reported that elevated production of specific proteins was required for resilient and sustained anti-malarial immunity in mice.

“

Nearly half a million people die from malaria every year, in part due to the lack of an effective

A research team led by Rongfu Wang, Ph.D., carefully dissected pathways in the immune system to identify a sensor in the genes that recognizes malaria DNA and activates interferon type I signaling

malaria vaccine and a limited understanding

following malaria infection.

of the body’s immune response during infection.

Current antimalarial drugs vary by country and are not 100 percent

We have identified immune system pathways

“

activated during infection and potential targets for a malaria vaccine.

– R ongfu Wang, Ph.D. Professor of Inflammation and Epigenetics Houston Methodist

protective, according to the World Health Organization. The Centers for Disease Control and Prevention reports that the malaria-causing parasite, Plasmodium falciparum, has developed resistance to nearly all of the available antimalarial drugs, including chloroquine, making this a serious global threat warranting new treatment options.

Wang hopes that his team’s findings will help researchers understand how lethal malaria blocks type I interferon signaling and how disturbing such signaling will aid in the development of effective anti-malaria vaccines for long-lasting malaria protection.

Yu X, Cai B, Wang M, Tan P, Ding X, Wu J, et.al. Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality. Immunity. 2016 Nov 15;45(5):1093-1107.

8

GENE DELETION POINTS WAY TO FLU TREATMENT

by Patricia Akinfenwa

Researchers at Houston Methodist kept mice from getting

Motif 29, controls activation of lung immune cells after viral

the flu by removing a gene that regulates their immune system.

infections. Zhang’s team infected mice without the gene

According to a study recently published in Nature Immunology,

with the H1N1 flu virus and compared their survival and

mice missing the gene TRIM29 eliminated human influenza

viral load to normal mice. Mice lacking TRIM29 survived

virus within 48 hours, protecting them from infection.

with no detectable infection or virus.

Immune cells around the lungs are the first line of defense

Xing J, Weng L, Yuan B, Wang Z, Jia L, Jin R, Lu H, Li XC, Liu YJ, Zhang Z.

against infections. The gene TRIM29, or Tripartite Interaction

tract. Nat Immunol. 2016 Dec;17(12):1373-1380.

Identification of a role for TRIM29 in the control of innate immunity in the respiratory

“ Influenza is a leading cause of death from infections worldwide.

An effective treatment is vital, especially for children, the elderly and patients with compromised immune systems. Mice that lacked TRIM29, were protected from a full-blown infection and completely cleared the virus, pointing the way to a potential flu treatment.

”

– Zhiqiang Zhang, Ph.D. Assistant Professor, Transplant Immunology in Surgery Houston Methodist

9

RESEARCH HIGHLIGHTS

Handle with Care: Sherrie and Alan Conover Center for Liver Disease & Transplantation

Portable Device Mimics Body Conditions to Keep Donor Livers Alive

10

by Maitreyi Muralidhar

For patients undergoing liver transplants, it is often their last hope for survival. These patients go through many years of complicated treatment regimens before turning to a transplant and they may only get one shot at it.

Ashish Saharia, M.D.

R. Mark Ghobrial, M.D., Ph.D.

In countries like the U.S., the demand for transplants

failure in a patient. According to transplant surgeon

is growing rapidly as people are living longer

Ashish Saharia, M.D., this could change very soon with

However, the supply of donor organs is far from

the availability of the Organ Care System™ (OCS) liver

keeping pace with demand.

device – a small, portable system that maintains the donor liver in physiologic conditions, closely

The supply-demand imbalance is just one part of

mimicking the normal body environment.

the equation. According to data from the United Network for Organ Sharing, almost eight percent of donated livers were unsuitable for transplants in 2016. This is high considering only 57 percent of people requiring transplants, actually got them.

The OCS device keeps the donor liver warm, which prevents fat cells from dying, while continuously perfusing it with oxygenated blood, antibiotics, steroids and other compounds, keeping the liver

Donor livers are rejected for many reasons, one

functioning like it would within the body. In fact,

of them being high fat content. Liver cells with

when inside the device, the liver even produces

high fat content can undergo lysis or breakdown

bile – a key indicator of liver function.

while being transported in ice, which is the standard method for transporting donor organs.

The OCS device also comes equipped with a

Transporting organs across the country can often

monitoring system that continuously measures vital

take several hours, which can make a usable liver

parameters of the liver and settings on the device can

unviable or increase the chances of transplant

be changed to keep parameters within the optimal

range. Blood circulating through the organ can be sampled and tested for several markers. Given that surgeons today

> 14,000

have limited ability to access or control the condition of livers during transport, this technology could be a game-changer by taking away much of the guesswork.

needed liver transplants

In addition, this device can potentially keep the organ viable for up to 24 hours. This would be a remarkable improvement over the current six-hour window of viability in ice, which limits the distances organs can be transported.

8,497

Saharia and a team of physicians led by principal investigator and Professor of Surgery, R. Mark Ghobrial, M.D., Ph.D,. at the Houston Methodist J.C. Walter Jr.

donated livers

Transplant Center and the Sherrie and Alan Conover Center for Liver Disease & Transplantation, are part of a clinical trial currently evaluating this device developed

by TransMedics©. The company has similar devices for

7,841

transporting donor hearts and lungs, both of which are awaiting FDA approval for commercial use.

liver transplants performed

Houston Methodist is one of only eight centers nationwide offering this trial for liver transplant patients. This study will test whether the new machine is as effective in preserving the donor liver as the method already in

8%

use today, which is storage in ice.

Randy Smith, the first patient in this clinical study at

donated livers unused

Houston Methodist, received a new liver transported using the organ care system in August 2016. The story of his experience and recovery was featured on the front cover of Houston Chronicle on December 13, 2016.

U.S. 2016 data sourced from United Network for Organ Sharing.

“ If this trial is successful, it will pave the way to expanding the

pool of donor organs available to patients with end-stage liver disease requiring a transplant. That would be a big step towards bridging the gap in organ availability.

”

– Ashish Saharia, M.D. Assistant Professor of Clinical Surgery Houston Methodist

11

RESEARCH HIGHLIGHTS

Cytotoxins contribute to virulence of

deadly bacterial infections Two toxins increase the severity of group A Streptococcus infections like "flesh-eating disease", according to a new report in The American Journal of Pathology.

by Gale Smith

Beginning in the mid-1980s, an epidemic of severe invasive infections caused by Streptococcus pyogenes (S. pyogenes), also known as group A streptococcus (GAS), occurred in the United States, Europe, and elsewhere. The general public became much more aware of these serious and sometimes fatal infections, commonly known as the “flesh-eating disease.” Potent cytotoxins produced by this human pathogen contribute to the infection. A new study in The American Journal James M. Musser, M.D., Ph.D.

of Pathology reports that the bacteria’s full virulence is dependent on the presence of two specific cytotoxins, NADase (SPN) and streptolysin O (SLO).

Bacteria produce cytotoxins that can cause cell death and result in infections of the deep fascia and other tissues, including necrotizing fasciitis. “Our research revealed that the most severe form of the disease requires two cytotoxins. If either one or both are missing, the infection is much less dangerous,” explained lead investigator James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine and Fondren Presidential Distinguished Chair at Houston Methodist.

12

“ We do not have a group A strep vaccine

that works right now. The information from this research may help develop more effective therapeutics, such as inhibitors of these two toxins, or even a vaccine.

”

– J ames M. Musser, M.D., Ph.D. Fondren Presidential Distinguished Chair Houston Methodist

To evaluate how the toxins SPN and SLO act together,

S. pyogenes could be controlled better because they

Musser's team, including Luchang Zhu, Ph.D. and Randy

were less likely to resist the bactericidal effects of human

Olsen, M.D., Ph.D., along with investigators at the National

polymorphonuclear leukocytes.

Institute of Allergy and Infectious Diseases used mice infected with genetically altered S. pyogenes strains that

According to the Centers for Disease Control and

produced either, both, or neither of the toxins. They found

Prevention, approximately 700 to 1,100 cases of

that mutant strains lacking either SPN or SLO or both do

necrotizing fasciitis caused by group A streptococcus

not cause the most severe forms of necrotizing fasciitis,

have occurred yearly since 2010. Although the disease

necrotizing myositis, bacteremia, and other soft tissue

primarily affects the young and old and those with

infections. Production of both toxins was required for full

underlying chronic conditions, it may also develop

infection virulence.

in healthy individuals. Transmission occurs personto-person, many times through a break in the skin.

Resistance to bacterial infections depends in part on innate immunity conferred by white blood cells, including polymorphonuclear leukocytes. The researchers found evidence that infections with SPN- and SLO-deficient

Zhu L, Olsen RJ, Lee JD, Porter AR, DeLeo FR, Musser JM. Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections. Am J Pathol. 2016 Dec 27. [Epub ahead of print]

13

EDUCATION NEWS

Amgen Scholar to Watch: Joy Wolfram, Ph.D.

by Thomas Ellington

Joy Wolfram, Ph.D., was recently named one of Amgen Scholars’ Ten to Watch – their top ten brightest up-and-coming scientists around the world. She’s also been honored as one of 12 internationally accomplished Finns as part of the 2017 Inspired in Finland campaign, a centennial celebration of Finland’s independence.

When it came time to choose a career direction, Wolfram

The Amgen program sponsored her first research project at

chose biomedical science because it presented a challenge

the Karolinska Institutet in Sweden where she contributed to

and the promise of answers to her curiosity about life. During

the discovery of a protein that accelerates cancer cell migration.

her time in college, this curiosity grew into a passion as she

Seeing the potential this research made, Wolfram realized that

consoled loved ones watching their relatives battle and lose

she wanted to engineer therapeutic applications of discoveries

their fight against cancer.

like this protein to help patients. She began her master’s work at the University of Toronto with this goal.

Just one year following her Ph.D., Wolfram's journey has

14

already taken her to five different countries – Finland, Sweden,

Her master’s thesis work focused on evaluating the performance

Canada, the United States, and China. While at the University

of promising antiangiogenic drugs in preclinical models. “Our

of Helsinki, in her homeland of Finland, Wolfram was awarded

results showed that the drugs worked for a while,” she said,

an undergraduate student travel grant from Amgen Scholars

“but ultimately they made the cancer worse.” Disillusioned with

– a research program supported by the philanthropic arm of

the ineffectiveness of this antiangiogenic strategy, Wolfram

the multinational biopharmaceutical company Amgen. She

decided to take a risk on an approach that she saw as more

didn’t know then, that almost ten years later, they would

innovative and full of promise – applications of nanotechnology

honor her again as one of their top ten alumni.

to cancer research.

EDUCATION NEWS

Clinical Translation Management Program Goes Online

As she searched the field of nanomedicine, she learned about the work of Mauro Ferrari, Ph.D. in transport oncophysics. Ferrari epitomized the kind of mentor Wolfram wanted to learn from – a pioneer and thought leader in translational research. He was leading the Houston Methodist Research Institute, purpose-built to pursue translational research and located in the heart of the world’s largest medical center. The Research Institute is not degree-granting but has affiliated doctorate degree programs around the world. Undaunted by geographic and language barriers, she reached out to Ferrari and joined his team at the Houston Methodist Research Institute as a graduate research fellow in 2011, and chose to earn her doctorate degree from the National Center for Nanoscience and Technology at the Chinese Academy of Sciences.

by Thomas Ellington

Wolfram didn’t speak Mandarin when she started, but learned the basics as

The 2017 University of St. Thomas (UST)

part of her thesis with coursework in the Chinese language, culture and history.

Master in Clinical Translation Management

In 2016, after splitting her time between China and the U.S. and publishing

is changing its format to meet the demands

36 research articles, Wolfram earned her Ph.D. in Nanomedicne. She has now

of learners outside the Houston metropolitan

accepted a faculty position at Mayo Clinic in Florida, and will continue to work

area. UST has worked with Houston

closely with investigators at the Houston Methodist Research Institute.

Methodist to redesign the program so that online coursework plus four week-long

Amgen Scholars chose Wolfram from their pool of over 3000 program alumni

in-person “residencies” will replace the

as one of the ten most promising up-and-coming scientists. This year, as

traditional structure of on-site lecture and

Finland celebrates 100 years of independence, they’ve marked the occasion

full-semester Houston-based capstone

by launching a media campaign recognizing 12 highly accomplished Finns.

project. The new residencies will include

Wolfram will stand alongside Nobel laureates, prominent authors, musicians,

immersive experiences in several locations

and sports stars to represent the best of Finnish talent.

in the U.S. and Europe at various life science companies.

Wolfram emphasized that she hopes to use this campaign as a platform to encourage other young people to study abroad, noting her own international

The program is currently accepting

exploration as critical to her success. “Science is everywhere, but it’s also a small community,” says Wolfram. “If you need a specific technique to advance

applications for its third cohort. The last

your research, it may be unlikely you’ll find it in your own country. You must be

round of applications is due by June 30,

aware of the whole scientific community and not be afraid to venture out to

and the program will begin in August 2017.

discover it.”

Visit stthom.edu/mctm for more information.

Challenges in health care – in science generally ­– are so big you can’t isolate yourself to solve these problems. It needs to be a global effort.

“

“

– Joy Wolfram, Ph.D. Postdoctoral Fellow Houston Methodist

15

AWARDS & ACCOLADES

OF INTEREST

Barbara Lee Bass, M.D., appointed President-Elect of the American College of Surgeons John F., Jr. and Carolyn Bookout Presidential Distinguished Chair Barbara Lee Bass, M.D., was named president-elect of the American College of Surgeons (ACS) at the organization’s annual Clinical Congress on October 19, 2016, in Washington, D.C. Bass is the chair of the Department of Surgery at Houston Methodist Hospital and the executive director of the Houston Methodist Institute for Technology, Innovation & Education (MITIESM).

She is internationally recognized for her scholarly contributions in the fields of surgical education, quality and outcomes sciences, and gastrointestinal and surgical oncology.

Bass has been a fellow of the ACS since 1988 and received its highest honor – the Distinguished Service Award – in 2013. She previously served as an ACS regent and chair of the board of governors. Bass will take the office of ACS president in October 2017.

American College of Surgeons

80K members

World’s largest surgical professional organization

Programs focused on surgical clinical care, education, health care policy and quality, and research.

16

OF INTEREST

Randa El-Zein, M.D., Ph.D., appointed to American Health Council Education Board Professor of Radiology Randa El-Zein, MBChB, Ph.D., was appointed to the Education Board at the American Health Council. This lifetime membership is awarded to only a select few considered to be among the top five percent in their field of specialty. A leading cancer researcher with a translational approach, El-Zein’s expertise lies in the area of biomarkers and their role in influencing predisposition to cancer. Her work focuses on understanding gene-environment interactions and cancer development.

As a member of the Education Board, El-Zein will share her extensive knowledge and experience in areas ranging from epidemiology to education.

John Cooke, M.D., Ph.D., recognized by AHA’s Circulation Research Editorial Board Research published by a Houston Methodist team led by John Cooke, M.D., Ph.D., received one of the five Best Manuscript Awards in 2016 for AHA’s Circulation Research journal. The journal’s editors chose Cooke’s paper “Proton Pump Inhibitors Accelerate Endothelial Senescence” because it met high standards of scientific excellence in terms of novelty, impact and methodology; it was widely read online following publication; and because the paper represented some of the best work published in Circulation Research.

Cooke, the paper’s senior author, and his team showed that chronic exposure to proton pump inhibitors (PPIs) accelerated biological aging in human endothelial cells, which line the inside of blood vessels. When healthy, human endothelial cells create a Teflon-like coating that prevents blood from sticking. When older and diseased, the endothelium becomes more like Velcro, with blood elements sticking to the vessel to form blockages. These findings are a progression of the work that Cooke and his team began more than five years ago. Cooke, who is the Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, wants to see more studies that focus on the impact of long-term use of these drugs on vascular health in a broader patient population.

17

OF INTEREST

BOARD OF DIRECTORS Houston Methodist Research Institute Steven D. Arnold

Mauro Ferrari, Ph.D.

David C. Baggett, Jr.

Antonio M. Gotto Jr., M.D., D. Phil.

John F. Bookout, Jr.

Mark A. Houser

John F. Bookout, III

Catherine S. Jodeit

Marc L. Boom, M.D.

Evan H. Katz

Timothy Boone, M.D., Ph.D.

Rev. Kenneth R. Levingston

Giorgio Borlenghi

Kevin J. Lilly

Carrie L. Byington, M.D.

Vidal G. Martinez

Joseph R. "Rod" Canion

Gregory V. Nelson

Albert Chao

Andrew C. von Eschenbach, M.D.

Augustine M.K. Choi, M.D.

Joseph C. "Rusty" Walter, III

Ernest D. Cockrell, II

Martha Walton

John P. Cooke, M.D., Ph.D.

Elizabeth Wareing

Dan O. Dinges

Judge Ewing Werlein, Jr.

Houston Methodist Research Institute Board Announcement

Greg Nelson, appointed chair of the Houston Methodist Board of Directors Greg Nelson has served on the Houston Methodist

vice chairperson. He has also served as chair of the

Research Institute Board of Directors for 8 years.

Houston Methodist Governance Committee and

During this tenure, he served as chair of the research

Finance Committee. Currently, Nelson chairs the

institute Board of Directors (2010-13) and as chair

President’s Leadership Council. He has also served

of the compliance committee. He took over as

as chair of the board of Memorial Assistance

the new chair of the Houston Methodist Board of

Ministries and has served Memorial Drive United

Directors on February 1. He is office chair of Paul

Methodist Church as its lay leader since 2003.

Hastings’ Houston office, one of the most successful and prestigious law firms in the world. Nelson has been listed in Best Lawyers in America for 15 straight years.

Nelson has served on the Houston Methodist board of directors since 2003 and as board secretary and

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A thoughtful, ethical and principled leader, Nelson has seen the Houston Methodist Research Institute grow from the time it was envisioned. He was involved in the onboarding of Mauro Ferrari, Ph.D., the current president & CEO of the research institute.

OF INTEREST

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UPCOMING EVENTS

UPCOMING EVENTS August 3, 2017

September 16, 2017

3 Annual Houston Methodist Orthopedics,

2017 Emerging Topics in Liver Disease

CME credit available

rd

Sports Medicine and Physical Therapy for the Primary Care Physician

CME credit available

August 18, 2017

September 19, 2017

City-Wide Pulmonary Conference

CME credit available

Houston Methodist Cancer Symposium

CME credit available

September 6, 2017 System Quality & Patient Safety Grand Rounds

Houston Methodist DeBakey Heart & Vascular Center Grand Rounds

CME credit available

CME credit available

September 13, 2017

2017 Sepsis Awareness Day Symposium

CME credit available

September 15, 2017 10th Annual Advances in Neurology

September 21, 2017

September 25, 2017

Novel Therapy for Brain Tumors

CME credit available

September 29, 2017

Endovascular Boot Camp

CME credit available

CME credit available Go to houstonmethodist.org/hpeventslist for more information.

METHODOLOGY The Research and Education Newsletter of Houston Methodist

Editor-in-Chief Rebecca Hall, Ph.D. Managing Editor and Writer Maitreyi Muralidhar, M.S. Copy Editor Thomas Ellington Design & Creative Lead Doris T. Huang

Contributing Writers Patricia Akinfenwa, Ph.D. Thomas Ellington Maitreyi Muralidhar, M.S. Gale Smith Katie Wooldridge Public Relations Contact Gale Smith 832.667.5843 gsmith@houstonmethodist.org

Read more online: issuu.com/instituteforacademicmedicine Office of Communications and External Relations Institute for Academic Medicine Houston Methodist news@houstonmethodist.org IAMNEWS-008 | 07.2017 | 1500