Boston Children's Hospital
Dr. Zhang is also Fred Rosen Professor of Pediatrics, Boston Children's Hospital, and a professor of genetics, Harvard Medical School and the Harvard Stem Cell Institute.
Mechanism and Function of Epigenetic Modifications
Every cell in the body has the same genetic information, yet cells can grow to be as different as heart and brain. To a large extent, the packaging of DNA designs the cells and presages their functions by controlling which genes are turned on or off during development. Understanding how those gene regulation instructions are passed to daughter cells is what drives Yi Zhang. He is a leader in the burgeoning field of epigenetics, where researchers are searching for the mechanisms that control gene expression that are independent of the DNA sequence itself.
Zhang has been probing the details of epigenetic modifications and their roles in fundamental biology and disease. His recent series of papers describes discovery of many of the enzymes known to modify the packaging of DNA by proteins known as histones, as well as by DNA itself. His work, which is mainly performed in tissue cultured cells and mice, uses a combination of biochemistry, molecular biology, cell biology, imaging, genetics, and behavioral biology.
Zhang and his colleagues have built the foundation for understanding the interactions between the different types of markers that change DNA packaging in ways that silence or activate genes, such as the addition of small acetyl, methyl, phosphate, and ubiquitin molecules. He demonstrated the importance of methylation and ubiquitination of histones, methylation of DNA in silencing an important group of genes that specify the proper location of body parts in developing organisms, and methylation in cell reprogramming. He and his colleagues also showed that the same modifications contribute to embryonic development and cell fate determination. In addition, they identified enzymes that can remove the methyl groups from histones and DNA and demonstrated the function of these reversible DNA and histone modifications in development and in diseases such as leukemia and metabolic syndromes.
Zhang plans to search for genes important for cancer drug resistance, cellular reprogramming, and drug addiction. He also wants to explore the role of epigenetic modification in stem cell biology, cancer, and the development of drug addiction.