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Stanford Medicine News Center - October 6th, 2015 - by Bruce Goldman, Jennie Dusheck, Rosanne Spector, and Bjorn Carey

Seven Stanford scientists have received awards totaling $11.5 million to pursue high-risk, high-reward research, the National Institutes of Health announced today.

They are among the 78 recipients of the 2015 Pioneer, New Innovator, Transformative Research and Early Independence awards from the NIH. The awards are designed to encourage scientists to pursue creative research projects with the potential of leading to big improvements in health care.

“Our scientists exemplify the spirit of excellence and innovation for which Stanford’s research program is known,” said Lloyd Minor, MD, dean of the School of Medicine, which is home to six of this year’s Stanford recipients. “I congratulate all of the award winners on this tremendous honor and thank them for helping Stanford Medicine lead the biomedical revolution in precision health.”

This year, the NIH handed out 13 Pioneer Awards, 41 New Innovator Awards, eight Transformative Research Awards and 16 Early Independence Awards. The total funding came to about $121 million.

This program has consistently produced research that revolutionized scientific fields by giving investigators the freedom to take risks and explore potentially groundbreaking concepts,” said NIH director Francis Collins, MD, PhD. “We look forward to the remarkable advances in biomedical research the 2015 awardees will make.”

Pioneer Award

Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, and a senior research career scientist at the Palo Alto Veterans Administration, received a Pioneer Award. The $2.5 million grant, dispensed over five years, goes to scientists proposing creative, potentially high-impact research in the biomedical and behavioral sciences.

Wyss-Coray’s group studies the role of immune and injury responses in brain aging and neurodegeneration, with a focus on Alzheimer’s disease. Wyss-Coray’s research has revealed insights into how functional defects in the brain’s own immune cells, microglia, can contribute to neurodegeneration, as well as how factors in blood can advance or retard cognitive decline.

Wyss-Coray plans to use his award to reprogram the genetic code in mice so that specific cells or tissues will synthesize proteins containing “designer” amino acids that can be chemically tagged. Researchers can then identify, track or isolate these proteins. This will allow researchers to study the collection of proteins within specific cell types and tissues during aging and in neurodegenerative diseases, including Alzheimer’s disease.

New Innovator Award

The New Innovator Award provides $1.5 million over five years to fund innovative research by an investigator who has not yet received a research project grant or the equivalent from the NIH.

Sanjay Basu, MD, PhD, assistant professor of medicine, specializes in the development of mathematical models that help improve disease-prevention programs, in part by predicting unexpected or adverse health consequences of public health, fiscal and regulatory policies. He investigates how such programs can help prevent chronic diseases, especially obesity and Type 2 diabetes, that disproportionately affect low-income populations around the world.

For example, his recent work on the Supplemental Nutrition Assistance Program found that adding grocery stores well-stocked with fresh produce in inner-city “food deserts” does not increase the amount of fruits and vegetables that people buy and eat. But preliminary work suggests that delivering food stamp benefits weekly instead of monthly may increase how much people spend on fruits and vegetables by encouraging weekly shopping at local stores instead of monthly shopping at big box stores. With his New Innovator Award, Basu plans to bring in two new postdoctoral scholars and purchase some expensive data sets that would otherwise be unavailable.

Basu is a member of the Stanford Prevention Research Center, an affiliate of the Stanford Center for Poverty and Inequality and a senior fellow of the Stanford Center for Innovation in Global Health.

Jessica Feldman, PhD, assistant professor of biology, studies cell specialization, which is a critical step in development and for normal physiology. Cells specialize by expressing different proteins that give them unique identities, but they must also shape and form themselves in unique ways to be able to carry out specific functions. 

A critical regulator of cell form is the microtubule cytoskeleton, a network of polymers that becomes spatially organized within cells during development. Feldman studies how this cytoskeleton forms in C. elegans, a tiny, transparent worm. She aims to understand the mechanisms that regulate microtubule organization during development, specifically the molecules that control and contribute to microtubule organization and how specific microtubule organization is coupled to the cell cycle and cell polarization.

Feldman will use the award to identify new molecules that link microtubules to specific sites in the cell, and also to uncover the regulatory mechanisms that control microtubule organization during development. She hopes that by understanding these basic principles, scientists can better understand the cause and consequences of aberrant microtubule organization that occurs in specific birth defects and in cancer.

Liang Feng, PhD, assistant professor of molecular and cellular physiology, will use his award to study the molecular mechanisms of Alzheimer’s disease and to explore new therapeutic strategies. During the course of this work, he plans to develop new tools that might also find applications in a variety of biological systems.

The Feng group has focused on proteins embedded in or anchored on biological membranes. These membranes act as selective barriers separating the interior of cells from their outside environment. Membrane proteins play crucial roles in a wide range of biological and physiological processes and are targeted by a large number of pharmacologically active compounds.

Feng’s research interest lies primarily in understanding the mechanism and regulation of these dynamic membrane proteins, and in developing new tools and approaches to understand their functions. To further that understanding, his group employs biochemical, biophysical, structural, computational and engineering approaches.

Juliana Idoyaga, PhD, assistant professor of microbiology and immunology, wants to create better treatments for autoimmune diseases. As many as 24 million Americans are affected by autoimmune diseases. There are currently no clinically approved therapies that can cure or prevent these diseases without causing side effects due to generalized immunosuppression.

Idoyaga’s research focuses on the function and biology of dendritic cells, which are specialized antigen-presenting cells that initiate and modulate our body’s immune responses. She aims to use her award to design new immunotherapies that harness the natural capacity of dendritic cells to generate antigen-specific regulatory T cells. These regulatory T cells can silence the undesired immune responses that lead to autoimmunity. She has found strong evidence in experimental models that engaging selected dendritic cell subsets can be used as a safe therapeutic approach for autoimmune diseases.

As a graduate student at the Massachusetts Institute of Technology, New Innovator Award recipient Daniel Jarosz, PhD, investigated how mutations are made in DNA. After graduating in 2007, he pursued postdoctoral training at the Whitehead Institute with Susan Lindquist, a pioneer in the field of protein folding. Jarosz joined the Stanford faculty in 2013 as an assistant professor of chemical and systems biology and of developmental biology. His research explores how organisms balance competing needs to retain their genetic integrity yet also adapt to new environments. Jarosz’s work has revealed that links between protein folding and environmental stress strongly influence the evolution of new traits, the effects of disease-related mutations and developmental processes.

Recently the team has investigated whether wrongly folded proteins are always a problem. Prions, which are misfolded proteins that act as templates to create more misfolded proteins, are best known for causing neurodegenerative disease. But Jarosz’s work in fungi suggests that they can also drive beneficial traits.

Jarosz plans to use his award for new work characterizing prionlike complexes formed by molecules that regulate cellular information flow: transcription factors and RNA binding proteins. 

Manu Prakash, PhD, assistant professor of bioengineering, works in the broad area of organismic biophysics and frugal science, developing low-cost, precision measurement tools for the masses. For example, he and his group invented the Foldscope, a $1 origami microscope assembled out of folded paper. Foldscopes are now being used by a worldwide community in applications ranging from environmental monitoring to science education. Foldscopes can also be configured for diagnostic applications, with ongoing field-validation studies in Kenya for a number of diseases including helminth infections and schistosomiasis. 

For his latest work, Prakash is studying disease vectors such as mosquitoes that transmit deadly diseases like malaria and dengue. These vector-borne diseases take a huge toll on human health. Yet no high-throughput, high-resolution tools exist for mosquito surveillance and the pathogens they harbor. With the support of this new award, Prakash aims to bring his low-cost, scalable design approach to creating a toolbox to enable the assessment of spatial-temporal population dynamics of mosquitoes and corresponding human pathogens in field conditions. If applicable broadly, these tools could provide a new window into host-pathogen dynamics in mosquitoes at ecological scales.

Originally published at Stanford Medicine News Center