Ramesh Shivdasani, MD, PhD
Harvard Medical School
A major focus in the laboratory is to understand molecular mechanisms of gut development, in particular the transcriptional control of epithelial differentiation and stem cell self-renewal.
The mucosa or cellular lining of the gastrointestinal (GI) tract is replenished every few days, a process that requires brisk stem cell activity. Furthermore, stem cells responsible for mucosal self-renewal are also believed to be the target and cell of origin of gastrointestinal cancers, such as colorectal cancer, the second leading cause of cancer death in the West. The GI tract originates from the endodermal germ layer in embryos and it develops in the context of significant epithelial-mesenchymal interactions that define tissue and cell relationships and functions. Present understanding about the molecular basis of gut development is incomplete and we know especially little about the distinguishing qualities of stomach and intestinal stem cells.
Nearly a trillion platelets circulate in the blood of an adult human and provide an essential defense against bleeding. Platelets originate within the cytoplasm of megakaryocytes, the largest of bone marrow precursors. Although megakaryocytes are exceedingly rare cells, they produce up to 100 billion blood platelets each day, and each megakaryocyte releases hundreds or thousands of platelets in a terminal event of cytoplasmic fragmentation.
The second major focus of the laboratory is to elucidate the molecular mechanisms that drive megakaryocytes to synthesize and release blood platelets.