Tamas L. Horvath, D.V.M., Ph.D., chair and professor of comparative medicine, and Haifan Lin, Ph.D., director of the Yale Stem Cell Center, have received 2010 Pioneer Awards from the National Institutes of Health (NIH).

The Pioneer Awards have been given annually since 2004 to scientists “of exceptional creativity who propose pioneering—and possibly transforming—approaches to major challenges in biomedical and behavioral research.”

In contrast to other NIH programs, the Pioneer Award Program aims to support a very small number of applicants. Horvath and Lin were among 17 scientists to be honored this year, and they join just 81 other researchers who have received the Pioneer Award since its creation. Each researcher will receive a $2.5 million grant as well as additional laboratory support over five years.

Lin, also professor of cell biology, is a world leader in understanding the role that bits of genetic material called small RNAs play in stem cell biology.

Until fairly recently, it was believed that an organism could not pass on changes in gene expression to future generations unless the DNA sequence of that organism’s genome was somehow altered, usually by mutations. But in recent years, it has become clear that additional mechanisms, known as epigenetic factors, can directly interact with the genome to prevent or enhance gene expression even if the underlying DNA sequence remains unchanged. Epigenetic processes have been implicated in congenital diseases, cancer, and autoimmune diseases, among others.

With the new grant, Lin will study how piRNAs, a class of small RNAs discovered in his lab, guide epigenetic factors to specific points within the genome. He ultimately hopes to compile information on epigenetic effects of small RNAs in the first “functional epigenome map.”

Horvath, co-director of the School of Medicine’s recently launched Program in Integrative Cell Signaling and Neurobiology of Metabolism, is an expert on the effects of metabolism on higher brain functions. He has studied neuroendocrine aspects of neurodegenerative diseases, and his research has also provided insight into metabolic disorders such as obesity and diabetes—his lab was the first to provide evidence that the brain uses fat as fuel.

Horvath has proposed that a small set of cells in the brain’s hypothalamus known as AgRP neurons are master regulators of energy utilization in all the body’s tissues. With his Pioneer Award, he will study how AgRP regulation of the cellular energy metabolism of various tissues affects the health and longevity of those tissues, and thus the life span of the entire organism.

Perturbations in AgRP function could contribute to many of late-onset chronic diseases, such as Alzheimer’s and Parkinson’s disease, diabetes, cardiovascular disorders and cancer.