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Praveen Sethupathy: MicroRNA, Regulation, and Complex Diseases

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Recommended by: Francis Collins, NIH

The genes expressed in a cell give that cell its identity and determine its function. Something, however, has to control that gene expression to give the cell stability in a changing environment. The University of North Carolina at Chapel Hill's Praveen Sethupathy wants to know how that control is regulated, particularly in disease. MicroRNAs, he says, are emerging as regulators of cellular robustness.

"That arena is exciting to me because I believe that it's going to advance our basic understanding of mechanisms that underlie this concept of cellular robustness, but it is also going to suggest novel therapeutic strategies for the diseases," he says.

Currently, Sethupathy is applying that idea to the study of type 2 diabetes. He is trying to identify which miRNAs govern the function of the pancreatic islet. "The hope is to be able to understand microRNA networks in ground state, and then be able to decipher how those network interactions — connectivity — is changing in the context of disease or islet dysfunction," he says.

To do so, he and his lab are combining computational and experimental genomics, beginning with next-generation sequencing and then moving to computational models to analyze their sequencing data before moving into cell cultures. For further in vivo validation, he adds, they team up with collaborators.

Publication of note

Sethupathy and his colleague in the Collins lab, Michael Stitzel, published a paper in Cell Metabolism in 2010 in which they profiled the epigenome of the pancreatic islet. This, Sethupathy says, was to better understand transcriptional regulation in the islet and provide insights into the etiology of type 2 diabetes.

And the Nobel goes to…

Rather than winning a Nobel Prize, Sethupathy would prefer to be recognized for helping his students. "If there was some sort of recognition about the impact you've had on your students or your colleagues, I think I'd be really happy about something like that," he says.

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