Dr. Robert A. Weinberg

Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research, Director of the Ludwig Center at MIT, Professor of Biology at MIT, and Associate Member of Broad Institute. Dr. Weinberg’s research has been focused over the past four decades on the molecular and biochemical determinants of neoplastic cell transformation and led to the discovery of the first functionally validated human oncogene (Ras) during 1979-81 and the isolation of the first validated tumor suppressor gene, RB, in 1986.

In subsequent years, this work led to the first experimental transformation of normal human cells into neoplastic cells in 1999. Since 2004, his group has been increasingly focused on the mechanisms by which the cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on carcinoma cells in primary tumors many of the traits required to invade and disseminate, resulting in the formation of metastases in distant sites. In addition to conferring on epithelial carcinoma cells traits such as motility and invasiveness, activation of this program heightens their resistance to chemotherapy. Among other discoveries, the lab demonstrated in 2008 that the EMT program could create de novo, carcinoma cells with the properties of cancer stem cells (CSCs), which are qualified to serve as founders of new metastatic colonies in distant anatomical sites.

Over the last decade, the overlap between the EMT program and cancer stemness has been explored in greater detail, leading to the discovery in 2015, that activation of a previously latent EMT program enables both normal and neoplastic epithelial cells to enter into a stem-cell like state through distinct mechanisms. Most recently (2022), the lab has also identified distinct, intermediate cancer cell-states within the E-M spectrum that have different metastatic capabilities, underscoring the importance of cellular plasticity during cancer progression.

Intriguingly, the lab has also recently discovered that the residence of cancer cells within different parts of the E-M spectrum influences their ability to differentially dictate their immune microenvironment and response to immune checkpoint blockade therapy, while also making them differentially vulnerable to an iron-dependent form of cell death, known as ferroptosis. The lab is also actively exploring the molecular mechanisms underlying these phenomena.

August 24, 2020

A Conversation with Dr. Robert Weinberg

Daniel K. Ludwig Professor for Cancer Research, Robert Weinberg, discusses spending his entire career at MIT — including earning an SB in 1964 and PhD in 1969, and becoming an assistant professor in 1973.