Four medical school faculty receive NIH awards for innovation

- By Erin Digitale

Brian Feldman

Brian Feldman

Innovative projects proposed by four School of Medicine faculty members have received funding from the National Institutes of Health through two programs that support high-risk research.

Brian Feldman, MD, assistant professor of pediatric endocrinology, has received one of this year’s NIH Director’s New Innovator Awards, which will provide him with $1.5 million in research funds over five years. The award is designed to support unusually creative investigators at an early stage of their careers. Two other researchers at Stanford — Lynette Cegelski, PhD, assistant professor of chemistry, and Alexander Dunn, PhD, assistant professor of chemical engineering — also received similar awards.

Two projects from the medical school — led by researchers Gary Peltz, MD, PhD; Marius Wernig, MD; and Thomas Sudhof, MD — also received Transformative R01 Awards. Both sets of awards were announced Sept. 30.

Feldman will use his $1.5 million New Innovator Award to study how hormones influence the fate of maturing stem cells.

His research on the basic biology of this relationship could lead to new therapies for a variety of diseases. In the long term, Feldman said, "We're trying to design new tools that will allow us to regulate stem cells in vivo. It might be possible to redirect stem cells towards more healthful lineages, or even induce their regenerative properties, without taking them out of a person." He imagines possibly heading off obesity by diverting stem cells away from the pathway that leads to fat cells, or treating muscle-wasting conditions by cueing stem cells to form more muscle.

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Gary Peltz

Feldman will use the New Innovator Award to develop experimental systems, such as transgenic mice, to examine the regulation of stem cell fate in living animals. His prior research has shown that the circadian clock, the body's mechanism for setting daily rhythms, is embedded in specific hormone signaling pathways that regulate stem cell fate decisions.

Feldman's lab is now creating transgenic mice with altered circadian clock function in their mesenchymal stem cells, the cells that give rise to tissues such as muscle, bone, cartilage andfat. The altered mesenchymal stem cells will be specially tagged with tracers to let the researchers follow them and reveal the potential of this approach to redirect stem cells' fates in a living animal.

The Transformative R01 Awards support projects that have the potential to create or overturn fundamental paradigms in biomedical research. The funding amount varies by project; in some instances, the funding amount has not yet been finalized.

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Marius Wernig

Peltz, professor of anesthesia — in collaboration with research associate Toshi Nishimura, MD, PhD, and postdoctoral scholar Yajing Hu, PhD — will use his $2.5 million award over the next five years to study the effects of common drugs, including cholesterol medications, on mice with livers grown from human liver cells. One of the liver's main functions in the body is to break down, or metabolize, toxic chemicals, which can include drugs.

"What we will do is determine if the rate of metabolism of drugs that we test is determined by the genetic factors within the donor human liver cells that are used to reconstitute the human liver," Peltz said.

He expects that some livers will process a given drug more quickly than others, which would potentially change the drug's effects on the body. This study could provide insight into why people's responses to the same drug sometimes vary.

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Thomas Sudhof

Wernig, assistant professor of pathology, and Sudhof, professor of molecular and cellular physiology, discovered earlier this year that skin cells taken from mice can be converted directly into fully functional neuronal cells, skipping the intermediary stem cell step. Wernig and Sudhof will use their award funding (the exact amount is still being determined) over five years to see whether the same technique can be used on skin cells from humans.

Neurons grown from cells of patients with brain disease would preserve the genetic information contained in the original cell, enabling scientists to study the cellular mechanisms of disease up close in a way that imaging studies and postmortem analyses do not allow.

This study will focus on neuropsychiatric diseases thought to arise from problems at the synapse – the space between neurons that signals must traverse to move from one cell to the next. But the potential is enormous.

"It could be applicable to any brain disease you can think of," Wernig said of the new method.

Sascha Zubryd is a science-writing intern for the school's Office of Communication & Public Affairs.

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