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2 UCSF scientists recognized for transformative research

Two UCSF scientists are among the 31 nationwide who have received 2008 New Innovator Awards from the National Institutes of Health. The awards are designed "to enable recipients to pursue exceptionally innovative approaches that could transform biomedical and behavioral science."

The grants, which provide $1.5 million in direct costs over five years, were awarded to Yuriy Kirichok, PhD, assistant professor of physiology, and Miguel Ramalho-Santos, PhD, assistant professor of obstetrics, gynecology and reproductive sciences and a researcher in the Institute for Regeneration Medicine.

Kirichok will study molecular mechanisms of cell energy production and cell death to open new avenues in the treatment of age-related metabolic and degenerative diseases. Ramalho-Santos will study the genetic mechanisms that control how stem cells specialize as many different cell types, research that has implications for regenerative medicine and cancer biology.

"These highly creative researchers are tackling important scientific challenges with bold ideas and inventive technologies that promise to break through barriers and radically shift our understanding," said NIH Director Elias A. Zerhouni, MD, who announced the awards on Monday, Sept. 22.

The programs, said Zerhouni, are central elements of NIH efforts to encourage and fund especially novel investigator-initiated research, even if it might carry a greater-than-usual degree of risk of not succeeding.

Kirichok is studying the dysfunction of the cell's mitochondria, which plays a key role in energy production and participates in such processes as cell-to-cell communication, cell differentiation, or specialization, cell death and cell cycle and growth. Dysfunction of mitochondria is implicated in neurodegeneration, obesity, diabetes, and cancer.

While pharmacological interventions at the level of mitochondria could become an effective way to treat these conditions, he says, the development of such therapies has been prevented by scientists' incomplete understanding of the molecular mechanisms that underlie major mitochondrial functions, including energy production, setting the pace of aging, and controlling cell death.

"The transport of ions and molecules across the mitochondrial membranes is the foundation of the mitochondrial physiology and a lack of direct methods to study mitochondrial transmembrane transport is likely the most significant barrier to a better understanding of mitochondria," he adds.

His goal is to develop a method for the application of the patch-clamp technique which revolutionized the study of ion channels and electrogenic transporters of the plasma membranes -- to both the inner and outer mitochondrial membranes for routine use in mitochondrial research. "This would provide an unparalleled functional essay for the key mitochondrial transport proteins, which, when combined with molecular biology, genetics, and protein crystallography, would facilitate significant advances in our understanding of the molecular workings of mitochondria and the subsequent development of therapeutic tools that control mitochondrial functions," he says.

Ramalho-Santos is studying the genetic mechanisms that give embryonic stem cells their capacity to differentiate, or specialize, into all of the cell types of the body. To date, most studies aimed at understanding this capacity, known as pluripotency, have been performed in the cell culture dish rather than in animal models.

During the last two years, however, his lab has gathered significant data in mice. In his upcoming work, his team will test the hypothesis that the genetic program for pluripotency plays an essential role in the development of germ cells, the precursors to eggs and sperm. To accomplish these goals, his team is exploring novel methods for rapid genetic manipulations in mouse germ cells.

By identifying the molecular mechanisms that regulate pluripotency, "it may be possible to tailor the differentiation of embryonic stem cells to particular cell types of choice that are need by patients, such as insulin-producing beta-cells in the case of diabetes," he says. "It may also be possible to safely and efficiently reprogram cells from patients to become pluripotent like embryonic stem cells. This will allow the generation of patient-matched embryonic stem cells that may be used to study the patient's disease in detail in the lab or to generate cells needed by the patient that would not be rejected upon transplantation."

Likewise, if the research is successful, he says, the team will have uncovered "routes towards preventing embryonic stem cell-induced tumorigenesis" and reversing the course of testicular cancer and potentially other cancers.


Contact: Jennifer O'Brien
University of California - San Francisco

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