Malcolm R. Whitman
Our lab studies signals that regulate the specification and maintenance of cell differentiation during early embryogenesis, tissue regeneration, and disease pathogenesis. We study embryogenesis and regeneration using frog embryos and tadpoles as a model system. We use primary cells in culture and animal models in collaboration with other laboratories to study the role of specific signaling pathways in disease pathogenesis and to test new approaches to disease therapy. Specific areas of current interest include:
Identification of a new approach to the treatment of chronic inflammatory disease. Halofuginone, a small molecule derived from the hydrangea root and used as an herbal anti-malarial therapy, has been found to be therapeutic for a variety of chronic inflammatory pathologies in animal models, but its mechanism of action is poorly understood. We have recently shown that halofuginone acts through a novel signaling pathway to regulate pro-inflammatory phenotypes. In collaboration with the lab of Dr. Anjana Rao (IDI) we have shown that this signaling pathway selectively inhibits the differentiation of a pro-inflammatory T cell subtype that has been implicated in a broad range of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and scleroderm. We also found that halofuginone effectively prevents disease pathology in a mouse model of multiple sclerosis. We are currently working to better understand the molecular mechanisms by which halofuginone activated signaling controls cell differentiation and pro-inflammatory phenotype, and to identify other diseases for which halofuginone may be a promising therapy.
Role of TGFßs in complex tissue regeneration. Xennopus tadpoles can fully regenerate their tails after amputation, re-forming organized muscle, nerves, and connective tissue. We have found that TGFß signaling is essential for this process, and are currently dissecting the multiple signaling steps that regulate regeneration of complex structures. We are developing new technical approaches to allow the visualization and molecular manipulation of discrete steps in the signaling cascades that control regeneration.
TGFß superfamily regulation of muscle size and development. Muscle size is negatively regulated by the TGFß ligand myostatin. The mechanisms controlling myostatin activity in vivo are poorly understood. We are currently studying signaling pathways that mediate the control of muscle size and function by myostatin. We are also interested in how autophagy may be regulated in muscle by signaling pathways that modulate muscle atrophy.
Dept. of Developmental Biology, REB 505
190 Longwood Avenue
Boston, MA 02115