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Following the Path from Basic Biology to Stem Cell Therapy
CHORI Scientist Wins Coveted NIH K18 Award
CHORI is pleased to announce that senior scientist Robert Ryan, PhD, Chair of the Center for the Prevention of Obesity, Cardiovascular Disease and Diabetes, has garnered a highly competitive National Institutes of Health (NIH) Career Enhancement Award for stem cell research, otherwise known as a K18 award. Established to address the urgent need for scientific expertise in the United States in the area of stem cell research, the K18 award was designed for both junior scientists who are trying to get training as well as established investigators like Dr. Ryan who wish to redirect their research toward the stem cell arena.

"Stem cells have incredible potential for use in treating disease, so there is a great deal of interest in trying to understand what it is that regulates their proliferation and differentiation," says Dr. Ryan. "This grant is a part of that overall effort."
“There is a great deal of interest in trying to understand what it is that regulates stem cell prolif-
eration and differ-
entiation.”

Pluripotent stem cells, regardless of whether they are cord blood stem cells or embryonic stem cells, naturally become any kind of cell in the body, from bone cells to tissue cells to organ cells, depending on how they are programmed by the body to develop. Researchers hope that understanding what is involved in the process by which one stem cell becomes one type of cell and another stem cell becomes a different kind of cell (differentiation) will allow them to harness that capability and direct it toward new therapeutic approaches to treat or cure disease.

"While the long term goal is to get to the point at which stem cells could be used as the basis for new therapeutic modalities, we are really only at the beginning of this process, " says Dr. Ryan.
“Before you can utilize the great potential inherent in stem cells, you first have to understand the basic biology, in particular how stem cells are regulated.”
With the new K18 grant, Dr. Ryan hopes to get closer to answering the critical question of stem cell regulation by combining his own research expertise in lipid transport and metabolism with that of Roel Nusse, PhD, a Howard Hughes Investigator at Stanford University, who is a premier researcher in the area of stem cell fate, and in particular, a family of regulatory agents, termed Wnt proteins.

"Wnt functions as a morphogen. In other words, it is secreted by one type of cell, and then goes on to affect the development of other cells in different parts of the body," Dr. Ryan says.

Dr. Nusse's extensive body of research has implicated Wnt proteins in the control and regulation of stem cell proliferation, and their differentiation into different kinds of cells. However, the protein is particularly challenging to investigate because it contains two covalently bound lipids, making it highly hydrophobic, or water resistant.
"This means the protein is poorly soluble in water, and that makes it very difficult to study," says Dr. Ryan. "At the same time, it's been shown that the lipid structure is essential to the Wnt protein's functional capability, it needs those lipids in order to maintain its optimal conformation to elicit its regulating affects on stem cell fate."

Dr. Ryan, however, has been pioneering a new biotechnology, called nanodisks, nanoscale-sized complexes of apoliprotein and phospholipid that are capable of interacting with hydrophobic molecules in order to make them water-soluble without changing the activity of the molecules themselves.

"Nanodisk technology is a way to solubilize hydrophobic materials so that they can be fully integrated into the blood stream for transportation and delivery to various cell types," Dr. Ryan explains.

Dr. Ryan and his colleagues at CHORI have already successfully utilized nanodisks as a means to solubilize anti-fungal and anti-cancer agents. The K18 grant provides Dr. Ryan with the unique opportunity to investigate a parallel application, which has profound therapeutic potential.

"The hypothesis is that combining nanodisks with the Wnt protein will stabilize Wnt, conferring solubility with retentions or enhancement in biological activity," says Dr. Ryan.

While the therapeutic endpoint of such research is still a long way off, the hope is that nanodisk-Wnt complexes will at a minimum provide a revolutionary new method for researchers to utilize on their way to fully understanding the basis of stem cell proliferation and differentiation, and the ways in which these cells may be used for novel therapeutic treatments.

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Tuesday, May 17, 2011 8:19 AM

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