Joslin also announced that it has recruited two top cell biologists, T. Keith Blackwell, M.D., Ph.D., and Amy Wagers, Ph.D., for the new section, joining long-time Joslin researcher Mary Loeken, Ph.D., who has transferred into the section.
"We're committed to moving stem cell research forward by bringing together top researchers in the field. Drs. Blackwell, Wagers and Loeken are all exceptional and talented scientists. Their combined research can help the Joslin research community continue to lead the way in the important area of stem cell research," says Joslin President C. Ronald Kahn, M.D. "The potential benefits of stem cells on type 1 diabetes make it vital to focus efforts with a new section."
Potential Benefits of Stem Cells
Many scientists believe that stem cell research holds tremendous promise for treating a variety of diseases, including diabetes. There are two basic types of stem cells: those that can multiply to make more copies of themselves ("self-renewing") and give rise to any type of cell in the body, and those that are self-renewing but are capable of yielding only a subset of cell types. Embryonic stem cells, derived from immature cells of the embryo, have the potential to give rise to any type of cell in the body – including the insulin-producing beta cells of the pancreas. The viability of islet cell transplantation, using pancreatic tissue containing insulin-producing beta cells, as a treatment for diabetes is severely limited by the lack of donor tissue and the need for powerful immunosuppressive drugs. Scientists hope that stem cells may someday provide a virtually unlimited source for insulin-producing cells, potentially freeing people with type 1 diabetes from the need for insulin injections.
Scientists also are very interested in adult stem cells, such as bone marrow or brain stem cells, which exist in tissues after birth, and are likely to give rise to a more limited number of cell types but may have significant therapeutic potential.
Scientists also believe that stem cells may someday help to prevent the devastating complications of diabetes, which include heart disease, stroke, peripheral vascular disease, diabetic retinopathy, kidney disease, nerve damage and birth defects. Many of these complications involve damage to large or small blood vessels. Stem cells show promise repairing blood vessels, so researchers hope that they might be able to undo some of the long-term damage that results from diabetes.
To unlock the therapeutic potential of stem cells, it will be necessary to understand the mechanisms that define and control their developmental capabilities, and that regulate their capacities for self-renewal and growth and adapting to particular environments. Studies of developmental biology thus go hand-in-hand with stem cell biology, because they will identify the control circuits that govern how stem cells function. In addition, while the ability to study human stem cells has opened up extraordinary new therapeutic opportunities, it is still necessary simultaneously to study stem cells in animal models, in which it is possible to perform a far greater range of experiments on how these cells function within the body. The Section on Developmental and Stem Cell Biology will create interactions and synergy among these complementary directions of stem cell research.
Learning Lessons from a Lowly Worm
T. Keith Blackwell, M.D., Ph.D., previously an investigator at the Center for Blood Research in Boston, will lead the Section on Developmental and Stem Cell Biology.
Dr. Blackwell's laboratory uses a simple model organism – the microscopic nematode (worm) Caenorhabditis elegans – to study the regulation of genes important for the development of germ cells, which form the sperm and egg, and the early embryo. Germ cells represent an important stem cell model because they can give rise to an entire organism. According to Dr. Blackwell, C. elegans is an excellent model organism because its genes can be readily manipulated. By studying how key control genes are regulated, Joslin hopes to discover exactly how embryonic cells differentiate into various types of cells, which may lead to insights into how to reprogram human stem cells to develop into different types of cell – including insulin-producing cells. In addition, Dr. Blackwell's work on germ cells in C. elegans is already uncovering basic principles of germ cell self-renewal and function that appear to be active in human embryonic stem cells.
Another major interest of the Blackwell lab is a gene-control circuit that in the early embryo initiates development of the digestive system, which includes the pancreas. This control mechanism later orchestrates one of the body's most important defenses against oxidative stress. Oxidative stress, or an excess of free radicals within the cell, is the major underlying cause of diabetic vascular disease and an important denominator of the health of insulin-producing cells. By understanding how these natural oxidative stress defenses are mobilized, Dr. Blackwell hopes in the future to identify new possibilities for antioxidant therapies that will combat or prevent diabetic complications.
Stem Cells Focus of Studies
Amy Wagers, Ph.D., recently joined Joslin from the laboratory of world-renowned stem cell researcher Irving Weissman, M.D., at Stanford University School of Medicine. She is studying the migration and function of blood-forming stem cells, which are capable of regenerating the entire blood system and one of the only types of stem cells currently used through bone marrow transplantation for the treatment of human diseases (including leukemia, lymphoma, immune deficiency and others). Transplantation of blood-forming stem cells may also be used someday to help people with diabetes, either by aiding in blocking the autoimmune process that causes type 1 diabetes, or by allowing patients to better tolerate islet transplants without the need for prolonged use of powerful immunosuppressive drugs.
In related studies, using strategies that previously have been successful in identifying precursor cells in the blood system, Dr. Wagers also is working to identify additional tissue-specific adult stem cell populations in bone marrow, skeletal muscle, the heart and the pancreas that may function robustly to regenerate or repair damaged adult tissues. The identification of such cells may have important implications for treating many of the long-term complications of diabetes. In addition, this comprehensive analysis of adult stem cell developmental potential will provide insights into the fundamental principles and limitations guiding adult stem cell function, and may ultimately suggest new treatment options for multiple degenerative disorders.
Birth Defects in the Offspring of Women with Diabetes Targeted
Long-time Joslin researcher Mary Loeken, Ph.D., who transferred from the Section on Cellular and Molecular Physiology, is studying the underlying causes of birth defects in diabetic pregnancy. Dr. Loeken and her colleagues have found that birth defects, which occur two to five times more frequently in the pregnancies of women who have diabetes, result from failure to induce specific genes needed to prevent cell death and induce differentiation at the very earliest stages of embryonic development.
Her laboratory has shown that pathways activated by excess glucose metabolism are responsible for the effects of diabetes on embryo gene expression. Embryonic stem cells can be used to study the precise biochemical and molecular mechanisms by which high glucose and oxidative stress prevent the activation of embryonic genes. If oxidative stress plays a significant role in causing birth defects, women with diabetes may someday be able to lower the risk of birth defects through dietary supplements that block oxidative stress. In addition, excess glucose metabolism may impair expression of many genes that contribute to the progression of diabetic complications in general, thus her research using the early embryo and embryonic stem cells may lead to new treatments for other complications of diabetes. An additional contribution of Dr. Loeken's research is studying the signals that make a stem cell start to differentiate into a specialized cell. Although she is studying the signals that make a stem cell turn into a nerve cell, similar signals are involved in making a stem cell into an insulin-producing beta cell.
"We see great potential promise in stem cells for someday preventing or halting diabetes, providing a vast supply of insulin-producing cells to transplant into individuals with diabetes, and for preventing diabetic complications. We're also keenly interested in exploring the effects of a mother's diabetes on the developing embryo so that we can minimize birth defects," says George L. King, M.D., Joslin's Director of Research. "We look forward to consolidating research in this area at Joslin."
Joslin Diabetes Center is affiliated with the Harvard Stem Cell Institute (HSCI). Funded by patient advocacy groups such as the Juvenile Diabetes Research Foundation (JDRF) and private foundations such as the Howard Hughes Medical Institute, HCSI was established in April 2004 in part to fill the funding gap caused by the Bush Administration's tight restrictions on federal funding for human embryonic stem cell research. HSCI researchers have already produced a number of human embryonic stem cell lines, which they are making widely available to medical researchers, in order to foster this extremely promising area of research. Another important purpose of HSCI is to create a community of investigators from the various Harvard-affiliated institutions that study stem cells in different tissue contexts and animal models, in order to maximize cross-pollination of information and ideas.
About Joslin Diabetes Center Joslin Diabetes Center, dedicated to conquering diabetes in all of its forms, is the global leader in diabetes research, care and education. Joslin Research is a team of over 300 people at the forefront of discovery aimed at preventing and curing diabetes. Joslin Clinic, affiliated with Beth Israel Deaconess Medical Center in Boston, the nationwide network of Joslin Affiliated Programs, and the hundreds of Joslin educational programs offered each year for clinicians, researchers and patients, enable Joslin to develop, implement and share innovations that immeasurably improve the lives of people with diabetes. As a nonprofit, Joslin benefits from the generosity of donors in advancing its mission. For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.