Harvard University | Graduate School of Arts and Sciences | Harvard Medical School | Division of Medical Sciences

BBS Faculty Member - Ramesh Shivdasani

Ramesh Shivdasani

Department of Genetics

Dana-Farber Cancer Institute
Dept. of Medical Oncology, Dana Bldg., Rm. 720
450 Brookline Ave.
Boston, MA 02215
Tel: 617-632-5746
Fax: 617-582-7198
Email: ramesh_shivdasani@dfci.harvard.edu
Visit my lab page here.

Our laboratory studies molecular control of development and cell differentiation in the digestive tract.

The gastrointestinal tract is especially suited for molecular investigation of mechanisms that regulate lifelong stem cell self-renewal. Furthermore, because communication between endoderm (prospective epithelium) and its adjoining mesenchyme is critically important in gastrointestinal development and homeostasis, the digestive tract is a powerful model to study tissue-tissue interactions. The laboratory has identified novel regulators of cell differentiation, determined their functions in vivo, characterized the dynamic patterns of transcription factor expression in the embryonic mouse gut, and developed methods to investigate gene functions in cultured embryonic organ explants.

Developmental signaling is controlled by surprisingly few pathways, including Wnt, Hedgehog and Notch; we study how ubiquitous pathways signal through tissue-restricted transcription factors to generate diverse and specific cell fates. We have been using whole-genome analysis of transcription factor binding and histone modifications in intestinal epithelial cells to determine how regulatory factors interact with one another and with chromatin to produce tissue-specific outcomes in normal and malignant epithelial differentiation. These approaches combine the power of modern genomics with sound experimental models to understand how cells and tissues transition between alternative fates.

An important goal of the laboratory is to understand how cellular relationships established in embryos are subverted in cancer. We especially seek to characterize processes that are active in development and silent in the normal adult tissue, but reactivated in tumors. Such processes shed light on developmental mechanisms relevant to tumorigenesis and reveal aspects of the disease that may be amenable to novel therapies.

Last Update: 6/12/2014

Publications

For a complete listing of publications click here.

Verzi MP, Shin H, He HH, Sulahian R, Meyer CA, Montgomery RK, Fleet JC, Brown M, Liu XS, Shivdasani RA. Differentiation-specific histone modifications reveal dynamic chromatin interactions and alternative partners for the intestinal transcription factor CDX2. Dev Cell 2010; 19:713-726.

Kim T-H, Kim B-M, Mao J, Rowan S, Shivdasani RA. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development 2011; 138:3225-3233.

Verzi MP, Shin H, San Roman A, Liu XS, Shivdasani RA. Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol 2013; 33:281-292.

Kim T-H, Li F, Ferreiro-Neira I, Ho L-L, Luyten A, Nalapareddy K, Long H, Verzi MP, Shivdasani RA. Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature 2014; 506: 511-515.