T. Keith Blackwell, M.D., Ph.D.
Dr. Blackwell is an Associate Director of Research, a Senior Investigator and co-head of the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center. He also is a Professor of Pathology at Harvard Medical School. He received his medical and doctoral degrees from Columbia University, where he studied with Frederick W. Alt, Ph.D., a leader in immunobiology and cancer biology. He trained as a postdoctoral fellow with the late Harold Weintraub, M.D., Ph.D., a pioneer in gene regulation and cellular differentiation. Dr. Blackwell received the Searle Scholar Award as an outstanding junior faculty member in 1995 while a Junior Investigator at the Center for Blood Research and Harvard Medical School; in 2001 he became an Investigator at the Center for Blood Research.
Stem cells have the potential to transform the future of medicine. Many scientists believe that stem cell research holds significant potential to help people with a variety of diseases, including type 1 diabetes. Embryonic stem cells are undifferentiated precursor cells that function like blank slates, capable of replication and able to develop into any type of cell in the body, including insulin-producing islet cells. The ultimate self-renewing stem cells are germ cells, which become egg or sperm cells. Germ stem cells are “multipotent,” able to develop into any cell in an entire organism.
In January 2004, Joslin Diabetes Center established the Section on Developmental and Stem Cell Biology, headed by Dr. Blackwell. Under his leadership, the section is assembling a core group of developmental biologists who are exploring the potential therapeutic value of stem cells for type 1 diabetes and certain diabetic complications.
Within the section, the Blackwell laboratory works primarily on two projects, each addressing an important problem in diabetes. One area is oxidative stress, the cellular and tissue damage caused by elevated levels of free radicals (a byproduct of metabolism). Oxidative stress also can result from chemical toxins and elevated glucose levels found in patients with diabetes.
Oxidative stress is an underlying cause of diabetic vascular disease, which gives rise to various diabetic complications. Understanding how to mount defenses against oxidative stress is likely to be of clinical benefit in treating diabetes, heart attack and stroke, and in preventing cancer.
In the second area, the Blackwell laboratory is using a simple model organism—the microscopic nematode (worm) Caenorhabditis elegans—to study specialized gene regulation mechanisms that are important for the development of oocytes (egg cells) and the early embryo. These gene regulation mechanisms may shed light on the powerful multipotent nature of the germ cell and on other specialized gene regulation mechanisms, such as those that store RNAs and proteins in these cells and allow them to follow differentiation programs appropriately.
Based on previous research, Dr. Blackwell and his colleagues believe that the gene regulation mechanisms in C. elegans stem cells may make significant contributions toward determining how to reprogram human stem cells to adopt particular differentiation pathways, including becoming insulin-producing cells. In the future, Dr. Blackwell would like to apply the knowledge gained in the C. elegans research to an investigation of the same regulation mechanisms in mouse and human stem cells.
Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EBE, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125:987-1001, 2006.
Boag PR, Nakamura A, Blackwell TK. A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C. elegans. Development 132:4975-4986, 2005.
Inoue H, Hisamoto N, An JH, Oliveira RP, Nishida E, Blackwell TK, Matsumoto K. The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19:2278-2283, 2005.
An JH, Vranas K, Lucke M, Inoue H, Hisamoto N, Matsumoto K, Blackwell TK. Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc Natl Acad Sci U S A 102:16275-16280, 2005.
Walker AK, Shi Y, Blackwell TK. An extensive requirement for transcription factor IID-specific TAF-1 in Caenorhabditis elegans embryonic transcription. J Biol Chem 279:15339-15347, 2004.
Page last updated: October 21, 2014