Faculty Member


Piyush Gupta

Piyush Gupta

Member, Whitehead Institute

Associate Professor of Biology, MIT


Gupta Lab


Our laboratory investigates the mechanisms that drive cancer progression and the acquisition of therapy resistance. We seek to define how the differentiation states of cancer cells influence their malignant behavior; and to decipher how the phenotypic plasticity of cancer cells drives tumor evolution in response to the selective pressures associated with cancer progression and treatment. To those ends, we deploy and develop a range of interdisciplinary experimental strategies, including high-throughput genetic and chemical screens, in vivo and ex vivo models, and new quantitative models and analyses for extracting information from large datasets—encompassing both laboratory studies as well as clinical datasets associated with patient tumors.

Piyush Gupta studies the mechanisms that generate and maintain cellular diversity in adult tissues and how the subversion of these mechanisms contributes to cancer. His laboratory investigates the genetic and cellular processes that govern adult and cancer stem cell self-renewal and differentiation. An improved comprehension of these processes is of fundamental interest in biology and would also facilitate the development of therapies for a broad range of diseases including cancer.

The mammary gland is well-suited for studies of tissue regeneration and homeostasis since its epithelium compartment must undergo regenerative proliferation, terminal differentiation and regression during each cycle of pregnancy and lactation. Moreover, the mouse mammary gland is an excellent system for studies of stem and progenitor cell biology, since the epithelial portion of the gland can be cleared and reconstituted via transplantation of donor cells.  Using a combination of experimental, technological and computational approaches, the Gupta laboratory is developing novel methods to probe and elucidate the cellular and signaling processes that control mammary stem- and progenitor-cell behavior.

A second area of interest for the laboratory is characterizing how perturbations in cell-state regulation contribute to cancer progression and therapy resistance. Cancer cells acquire malignancy in proportion to the degree to which they are able to access primitive stem- and progenitor-like states that are normally restricted to cells within specialized tissue niches. The ability to access stem-like states enables cancer cells to survive many forms of therapy and also promotes metastatic progression. The Gupta laboratory is working to elucidate the signaling mechanisms that facilitate entry of cancer cells into more primitive states. The laboratory is also studying the signaling mechanisms activated in these primitive states that enable cancer cells to become highly malignant.  

Finally, Gupta is interested in the role of stochasticity in fate decisions at the single-cell level. Gupta’s laboratory is using a combination of experimental and computational approaches to build stochastic models of state transitions in cellular populations. These studies will shed light on how tissues maintain phenotypic equilibrium even with inherent randomness in molecular processes.

Piyush Gupta studied Mathematics and Biological Chemistry at the University of Chicago. He received his Ph.D.in biology from MIT in 2006 and conducted post-doctoral research with Eric Lander at the Broad Institute. He was appointed a faculty member in the department of biology at MIT and a Member of the Whitehead Institute in 2010.

Selected Achievements

  • Demonstrated that the epigenetic state of cells strongly influences cancer phenotypes following neoplastic conversion
  • Developed a systematic method for discovering agents with selective toxicity towards cancer stem cells
  • DOD Breast Cancer Predoctoral Fellowship (2001)
  • Smith Family Scholar Award (2011)

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