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Mark of Excellence
CHORI Senior Scientist Robert Ryan, PhD Wins NIH MERIT Award

CHORI is pleased to announce that Senior Scientist Robert Ryan, PhD, of the Center for the Prevention of Obesity, Cardiovascular Disease and Diabetes, is a 2010 National Institutes of Health (NIH) Method to Extend Research in Time (MERIT) Award recipient. One of the most coveted and distinguished awards available, the MERIT award is given to less than five percent of NIH researchers.

“It demonstrates that Dr. Ryan is a leader in his field and that his research is recognized as having made major contributions to his area of study,” says CHORI Executive Director Alexander Lucas, PhD.

”To be recognized by the MERIT program is to be exceptional.”


NIH MERIT Awards convert existing NIH R01 research grants, which generally require renewal procedures on a two to five year basis, into ten-year grants during which time researchers do not have to bear the administrative burdens of renewals.

"It's not only an incredible honor, but MERIT Awards are also of huge benefit to researchers," says Dr. Lucas. "Meeting the rigorous demands of grant renewal can be very time consuming. It allows a great deal of breathing room to focus entirely on the research itself."

Those who receive MERIT awards do not apply for them. Instead, recipients are chosen by program staff at the respective NIH institutions, in this case, the National Heart Lung and Blood Institute (NHLBI). The NHLBI selects MERIT Award recipients on the basis of their exceptional talent and imagination, as well as on their record of preeminent scientific achievement and contributions of lasting scientific value.

"I've had the original grant for as long as I've been at CHORI, since 2000. I've been lucky enough to have it renewed twice, and now, to have it converted into a MERIT Award," says Dr. Ryan.
“While I am very grateful for the continued support, I can't emphasize enough, that whatever success this grant has had is the result of our lab as a whole.”
"We've assembled a fantastic team of people who are motivated and dedicated scientists, and they are really the reason for the progress we've made at the bench. CHORI also has a team of specialists and administrators who do all the other things related to grant management that I'd rather not think about. Without this whole team, none of this would be possible," says Dr. Ryan.

The winning grant, entitled Effect of Apolipoprotein Structural Adaptability, is geared toward understanding the structure and functional mechanisms of apoliprotein E (apo E) – a protein that transports lipids through the bloodstream – and apo E's binding mechanisms with low density lipoprotein receptor (LDLR), a critically important player in diseases related to cholesterol metabolism.

"We know both apo E and LDLR are important because knockout mice that are genetically engineered to lack these show a much greater increase in heart disease. We also know that one of the three different structural forms of apo E, apo E4, is linked to early onset Alzheimer's disease (AD)," says Dr. Ryan. "We are trying to clarify the mechanisms by which apo E and LDLR regulate these diseases."

Throughout the course of the grant, Dr. Ryan's team will be using a novel technique to evaluate apo E and LDLR, called expressed protein ligation, which allows researchers for the first time to study apo E at high resolution while it is actually in a lipid-bound state, as well as while it is bound to LDLR.

"One of the real bottlenecks in structural biology has been the study of lipid-bound systems, including proteins like apo E that function primarily when they are bound with lipids," explains Dr. Ryan. "Expressed protein ligation allows us to simplify the complexity of lipid-bound systems by selectively labeling only one portion of the protein at a time. It allows you to interpret your data with much greater clarity in order to truly understand what the interaction is between apo E and LDLR."

Dr. Ryan hopes to be able to utilize expressed protein ligation to illuminate fundamental questions regarding how a single amino acid difference between apo E4 and other apo E forms can cause such a dramatic affect, as well as how LDLR and apo E interact to make sure that lipids are delivered to their correct locations.

"By understanding the nature of apo-E interaction with other proteins, how those interactions occur, and what might be modifying those interactions, we hope to elucidate the fundamental mechanisms that get at the root cause of both coronary heart disease and AD," says Dr. Ryan.

"Understanding the mechanism of disease ultimately provides an opportunity to develop new strategies to diagnose, prevent and treat these debilitating diseases that have such an impact in our society today."
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Tuesday, May 17, 2011 8:19 AM

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