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Three OHSU scientists earn $2.25 million to accelerate innovation, collaboration

Inaugural Faculty Excellence Awards will fund research in marijuana use in pregnancy, new therapies for heart disease, leukemia
Jeffrey Tyner, Ph.D., lab setting. Jeffrey Tyner, Ph.D., above, Steven Mansoor, M.D., Ph.D., and Jamie Lo, M.D., MCR, are the first recipients of the new Faculty Excellence and Innovation Award. (OHSU)
Jeffrey Tyner, Ph.D., above, Steven Mansoor, M.D., Ph.D., and Jamie Lo, M.D., MCR, are the first recipients of the new Faculty Excellence and Innovation Award. (OHSU)

A new award, made possible by the Silver Family Innovation Fund, recognizes exceptionally creative early- and middle-stage investigators with a total of $750,000 for each researcher over three years.

Jeffrey Tyner, Ph.D., Steven Mansoor, M.D., Ph.D., and Jamie Lo, M.D., MCR, are the first recipients of the new Faculty Excellence and Innovation Award.

Peter Barr-Gillespie, Ph.D.
Peter Barr-Gillespie, Ph.D.

“These scientists and physician-scientists represent the next generation of faculty leaders at OHSU,” said Peter Barr-Gillespie, Ph.D., OHSU chief research officer and executive vice president. “Obtaining unrestricted funds like the Faculty Excellence and Innovation Award early in your career is a fantastic boost to your research program. For these creative scientists, such funds will allow them to take additional scientific risks, which may lead to extraordinary intellectual payoffs in the future. I am confident that these investments will not only catalyze innovation in these scientists’ labs but also spark new collaborations, which may benefit many other scientists at OHSU as well.”

OHSU deans, directors and chairs nominated candidates from their respective schools, programs and departments, and applications were reviewed by prominent scientists from institutions around the country. A new round of funding will be announced in spring 2020. Only early- and mid-career scientists are eligible.

 

Awardee profiles

 

Jamie Lo, M.D.
Jamie Lo, M.D.

Jamie Lo, M.D., MCR

Assistant professor of obstetrics and gynecology (perinatology and maternal-fetal medicine), OHSU School of Medicine; Reproductive & Developmental Sciences, OHSU Oregon National Primate Research Center

Understanding how chronic exposure to marijuana in pregnancy affects infants 

Prenatal marijuana exposure has been associated with stillbirth, low birth weight and problems with offspring brain development and behavior. It also is the most commonly used federal illicit drug in pregnancy. Although multiple organizations, including the Surgeon General, American College of Obstetricians and Gynecologists, and American Academy of Pediatrics, all advise pregnant and lactating women to abstain from marijuana use, many continue to use, given the lack of robust safety data. Because marijuana is commonly used to help with morning sickness during the first trimester — the period that is most critical for the vulnerable and developing fetus — there is an acute need to better understand the effects of marijuana-containing products during pregnancy and breastfeeding.

In response to the growing prevalence of prenatal marijuana use, the National Academies of Sciences, Engineering, and Medicine recently identified and prioritized critical research gaps, including limited evidence on prenatal or perinatal outcomes from maternal marijuana use; a need to study newer cannabis products with present-day THC doses; and a need to study the effects of THC only.

“All patients deserve to know the potential effects that marijuana may have on their developing child. My research vision is to address these important research gaps by developing an innovative nonhuman primate model that overcomes barriers in human research and facilitates understanding of the prenatal and postnatal effects of chronic maternal marijuana use during pregnancy,” said Lo. “This knowledge is sorely needed to accurately inform thousands of mothers who use marijuana and marijuana-derived products of any risks that might be associated with their use.”

The award will allow a multidisciplinary approach, synergizing the scientific collaborations of the OHSU OB-GYN Department, Oregon National Primate Research Center, and Advanced Imaging Research Center. Investigations into the effects of chronic prenatal marijuana use on the developing brain will inform new avenues of prenatal substance use research. Ultimately, this funding will deliver new insights regarding the impact of chronic prenatal marijuana use and facilitate the design of human studies. Lo’s long-term goal is to establish evidence-driven recommendations and frame policy guidelines for marijuana use in pregnant and lactating women.

Steven Mansoor, M.D., Ph.D.
Steven Mansoor, M.D., Ph.D.

Steven Mansoor, M.D., Ph.D.

Assistant professor of medicine (cardiovascular medicine) and chemical physiology and biochemistry, OHSU School of Medicine; OHSU Knight Cardiovascular Institute

Determining the structure and function of cardiovascular proteins to treat heart disease

The structure and function of proteins, especially complex cell surface receptors such as ion channels, are critical to cellular physiology and signal transduction, and to the pathophysiology of disease. Despite their central function in human physiology and as potential targets of therapeutic agents, we do not have enough information about their structure to design drugs that could specifically target these receptors.

As Mansoor sought treatments for his patients, he wondered how protein receptor signaling really worked and whether it could be strategically manipulated to alter physiology or even treat disease. This led him to study the relationship between the structure and function of these proteins.

“The structure-function relationship of proteins sits at the heart of these questions,” said Mansoor. “The further I got in my medical training, the more I realized that this relationship is fundamentally important to pharmacology and to the majority of medicines I use daily to treat patients with cardiovascular disease.”

Understanding the structure of receptor drug targets and how ligands influence that structure, and ultimately, the receptor’s function will allow for the rational design of pharmaceuticals for the treatment of cardiovascular conditions such as angina, hypertension and platelet aggregation.

Mansoor is investigating purinergic receptors, which play important roles in cardiovascular, neuronal and immune systems. The award will allow him to use single particle cryo-electron microscopy, X-ray crystallography and techniques in electrophysiology to study the structure, function and signaling of these receptors. This will span studies of ligand/receptor interactions at the bench to the development of novel drug therapies that will be tested for safety in animals and efficacy in humans, through clinical trials, to ultimately treating patients with cardiovascular disease at the bedside.

Jeff Tyner, Ph.D. (2018)
Jeff Tyner, Ph.D.

Jeffrey Tyner, Ph.D.

Professor of medicine (cell, developmental, and cancer biology), OHSU School of Medicine, OHSU Knight Cancer Institute

Working toward a cure for blood cancers 

The goal of Tyner’s research program is to improve therapies for patients with leukemia and other blood cancers through a discovery-based platform of functional genomics. Several of his findings have been, and are being, tested in clinical trials, the earliest of which are now complete and likely to lead to regulatory approvals.

The basic premise of this functional genomics platform is to collect as much information as possible from samples of patient cancers — information such as analyses of tumor cell drug sensitivity, signaling, genetics and other cellular processes, as well as data regarding the state of the tumor microenvironment — to mine these expansive patient sample data sets and perform complementary experiments using laboratory models.

Tyner said that he had applied this research strategy to the study of numerous forms of these cancers for more than 10 years: “My team has made a number of discoveries that have led to better understanding of the origins of these diseases. When we couple these biological insights with clinically oriented information, we can make significant advances in the manner by which blood cancers are diagnosed and treated.”

With the Faculty Excellence and Innovation Award, Tyner will further develop the platforms his team is using to study these hematologic malignancy patient samples. In particular, they will be able to incorporate more sophisticated and precise analyses of cancer cell phenotypes with single-cell granularity. This data generation will be coupled with expansive mechanistic follow-up experimentation that will enable prioritized testing of novel drug combinations.

The culmination of the whole research program will support clinical trials to be developed for novel drug combinations to improve outcomes for patients with cancer.

Silver Family Innovation Fund

Faculty Excellence and Innovation Awards nominees, Fall 2019

Deans, directors and chairs at OHSU were asked to nominate a single faculty member for the Faculty Excellence Awards. These nominees represent some of the most accomplished early- and middle-stage investigators at OHSU and are among the most promising thinkers in their fields.

*Finalists.

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