Dr. James D. Griffin - CML - Chronic myeloid leukemia
''James D. Griffin, MD, is a professor of medicine at Harvard Medical School and an attending physician at the Dana-Farber Cancer Institute in Boston, Massachusetts...
Dr. Griffin has studied the function of tyrosine kinase oncogenes that cause AML and chronic myelogenous leukemia (CML), including Flt3 and bcr-abl. He has been a leader in studying signaling pathways activated by the oncogenes. This work, and the model systems he devised to do these studies, have contributed to the development of small-molecule tyrosine kinase inhibitors currently used for therapy in both CML and AML. ''
Abstract of http://www.bloodline.net/bloodline-reviews-edufeatures-45/26-blr51
''Research Abstract
Dr. Griffin's laboratory is focused on understanding the genetic events that cause leukemia. The major laboratory interests can be divided into three broad areas: 1. Mechanisms of transformation by the BCR/ABL oncogene. The product of the BCR/ABL oncogene is an activated tyrosine kinase which induces a myeloproliferative syndrome in humans and mice. p210BCR/ABL transforms hematopoietic cells at least in part by constitutively activating signal transduction pathways which are normally tightly regulated by growth factors such as IL-3 or GM-CSF, such as those involved in blocking apoptosis. Several critical targets of BCR/ABL have been identified, including CRKL, SHP2, PI3K, SHIP, and RAS. Defining the individual contribution of each pathway to CML is underway, as are gene discovery approaches to identifying novel targets. 2. Mechanisms of transformation by the FLT3 oncogene and development of targeted therapies against FLT3. FLT3 is mutated in about 35% of all cases of AML. The lab has developed a small molecule tyrosine kinase inhibitor that blocks signaling from FLT3, which is currently being tested in clinical trials. In vitro studies of mechanism and murine models are being used to develop the next generation of AML therapies using this inhibitor as part of the therapy. 3.Signaling of the Notch receptor in hematopoietic and epithelial cells. We have recently cloned a several nes members of the Notch signaling pathway, a family of transcriptional regulators (mastermind-like genes) that modulates expression of Notch regulated genes in a variety of cell lineages. One family member, MAML2, has recently been shown to be mutated in mucoepidermoid cancer and appears to be the cause of that neoplasm.''
Extract of http://www.dfhcc.harvard.edu/membership/profile/member/1273/0/
