Dr. Blackwell was born in Greenville, SC. He received his BS degree in Chemistry from Duke University in 1978, and MD and PhD degrees from Columbia University in 1987 and 1988, respectively. Dr. Blackwell performed his graduate work with Dr. Frederick W. Alt, studying how B- and T-cell antigen receptor genes are assembled.
In 1989 he joined the lab of the late Dr. Harold Weintraub (Fred Hutchinson Cancer Research Center, Seattle, WA) as a postdoctoral fellow of the Life Sciences Research Foundation. He then developed high-throughput systems for analyzing protein-nucleic acid interactions, and studied how regulatory proteins recognize DNA. This work eventually established the direction for his current work, investigating gene regulatory mechanisms involved in development, metabolism, stress defense, and aging.
In 1993 he became a Junior Investigator at the Center for Blood Research (now Immune Disease Institute or IDI, a medical research center affiliated academically with Harvard Medical School and focused on inflammation and the immune response), and an Assistant Professor of Pathology at Harvard Medical School. Dr. Blackwell was promoted to Associate Professor in 2001, and Professor in 2008. He was named a Searle Scholar in 1995, and an Ellison Medical Foundation Senior Scholar in Aging in 2010. He has participated in numerous review panels at the NIH, and is a member of the editorial board of the journal Aging Cell.
In 2004, Dr. Blackwell moved his laboratory to Joslin Diabets Center, where he is Associate Research Director, co-head of the Section on Islet Cell and Regenerative Biology, and a principal faculty member of the Harvard Stem Cell Institute.
The Blackwell laboratory studies how cells and organisms defend themselves against environmental and metabolic stresses. These stresses include high levels of reactive oxygen species (ROS) and other potentially harmful products of metabolism, misfolded proteins, and perturbations in protein synthesis. We are particularly interested in understanding these how stress defenses influence the aging process. Cellular stress defenses are important in diabetes in several ways. For example, chronic elevations in blood glucose lead to high levels of ROS (oxidative stress) in endothelial tissues, one of the most fundamental causes of diabetic complications in both Type 1 and Type 2 patients. During Type 2 diabetes, the demand for insulin synthesis can place enormous stress on the beta cell endoplasmic reticulum, eventually leading to oxidative stress and beta cell demise.
Interventions that slow aging hold great promise for preventing Type 2 diabetes and other chronic diseases, including complications associated with both diabetes types, and for maintaining function of insulin-producing beta cells. The Blackwell lab studies how cells and tissues defend against environmental and metabolic stresses, and how these stress defenses influence aging. Much of our work involves the nematode C. elegans as a model organism, and many of our projects are centered on the gene transcription regulator SKN-1/Nrf, which responds to oxidative stress and reactive toxins, and plays a central role in various mechanisms that extend healthy lifespan. In humans, SKN-1/Nrf has been implicated in protection against diabetic complications. Our recent work has shown that SKN-1/Nrf mediates surprisingly broad spectrum of protective functions besides oxidative stress defense, including maintenance of proteasome function, the extracellular matrix, homeostasis in the endoplasmic reticulum, and lipid metabolism.
One important goal of the lab is to elucidate how signals and cooperating factors control SKN-1/Nrf so it can perform so many different functions. Another is to understand the involvement of these protective processes in determining lifespan. We have begun to unravel new mechanisms through which stress and metabolic signals regulate SKN-1/Nrf. We have also determined that SKN-1/Nrf is critical in relationships between cellular growth signals, protein synthesis, and aging. More recently, we have identified a novel mode of redox-based signaling that controls SKN-1 and many other cellular regulators. We are applying the advantages of C. elegans to develop new ideas and models for how master regulators such as SKN-1/Nrf maintain metabolic balance and promote healthy aging, so that we can translate these findings to human and other mammalian models.