Malcolm Whitman, PhD
Associate Professor
Department of Developmental Biology
Office: REB 505
Telephone: 617-432-1320
Email: malcolm_whitman@hms.harvard.edu

Whitman Lab web site

Click here for a list of Dr. Whitman's available publications in PubMed

Our laboratory studies signals that regulate the specification and maintenance of cell differentiation during early embryogenesis and tissue homeostasis in the adult, and how these signals are altered during disease pathogenesis. We use the frog embryo and tissue culture cells as model systems, and study primarily the regulation and action of the TGFβ superfamily of ligands. TGFβ superfamily members regulate a wide variety of biological processes, including the establishment of early embryonic body pattern, the formation and patterning of tissues and organ systems in later development, and the onset of pathological processes, including fibrosis and tumor metastasis, in the adult. One of our major goals has been to understand the basis for the tissue specific regulation of transcription that occurs in response to TGFβ signaling. We identified a transcription factor in early embryos, FAST-1, that specifically directs TGFβ signal transducers, the Smads, to early embryonic promoters. We are continuing to investigate how FAST-1 and other early embryo-specific transcription factors mediate patterning by TGFβs. Bone, cartilage, and muscle all depend on TGFβ signals for their maintenance and repair in the adult, as well as for their initial development. Muscle maintenance depends specifically on the TGFβ ligand myostatin, but neither the targets for myostatin action or the mechanism of its regulation in vivo are well understood. We are currently investigating both how myostatin may control muscle growth and wasting, as well as how the activity of myostatin and related factors are controlled in vivo.

Because aberrant TGFβ signaling is associated with a number of disease processes, including tumor metastasis, tools for the control of TGFβ signaling in vivo are of major clinical importance. We are currently working on several approaches to understand the mechanism of action of small molecule inhibitors of TGFβ signaling and how they can be used to inhibit specific pathological processes in vivo.