Director

Robert A.
Weinberg
Tumor biology
M.I.T. Center
Bio

I am Director of the Ludwig Center for Molecular Oncology at MIT, the Daniel K. Ludwig Professor for Cancer Research within MIT’s Department of Biology and a founding member of the Whitehead Institute for Biomedical Research. My co-workers and I isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene.

I’ve written or edited five books and more than 390 articles. My three most recent books, intended for a lay audience, are One Renegade Cell, Racing to the Beginning of the Road: The Search for the Origin of Cancer and Genes and the Biology of Cancer, co-written with Dr. Harold E. Varmus, former Director of the National Institutes of Health. I recently published the second edition of my widely used textbook The Biology of Cancer.

Born in Pittsburgh in 1942, I received my BS (1964) and PhD (1969) in Biology from MIT and performed postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California. I returned to MIT in 1972.


Achievements

I’m an elected Member of the U.S. National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences. Among a number of honors and awards, I’ve received the Discover magazine 1982 Scientist of the Year, the Sloan Prize of the General Motors Cancer Research Foundation, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, and the 1997 National Medal of Science.

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Host: 

The Ludwig Center for Molecular Oncology is housed within the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology.
 

M.I.T. Center

Director

Robert A.
Weinberg
Tumor biology
M.I.T. Center
Bio

I am Director of the Ludwig Center for Molecular Oncology at MIT, the Daniel K. Ludwig Professor for Cancer Research within MIT’s Department of Biology and a founding member of the Whitehead Institute for Biomedical Research. My co-workers and I isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene.

I’ve written or edited five books and more than 390 articles. My three most recent books, intended for a lay audience, are One Renegade Cell, Racing to the Beginning of the Road: The Search for the Origin of Cancer and Genes and the Biology of Cancer, co-written with Dr. Harold E. Varmus, former Director of the National Institutes of Health. I recently published the second edition of my widely used textbook The Biology of Cancer.

Born in Pittsburgh in 1942, I received my BS (1964) and PhD (1969) in Biology from MIT and performed postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California. I returned to MIT in 1972.


Achievements

I’m an elected Member of the U.S. National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences. Among a number of honors and awards, I’ve received the Discover magazine 1982 Scientist of the Year, the Sloan Prize of the General Motors Cancer Research Foundation, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, and the 1997 National Medal of Science.

Read More

Host: 

The Ludwig Center for Molecular Oncology is housed within the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology.
 

Ludwig Center at MIT
77 Massachusetts Avenue, 76-158
Cambridge, MA, us, 02139
T 617 258 5159
F 617 258 5213

Our Center at MIT is focused on the processes associated with malignant progression, specifically on the mechanisms that allow cancer cells originating in primary tumors to disseminate and ultimately form metastatic colonies. This multi-step process involves a series of cell-biological and biochemical changes in malignant cells, which are being investigated at several levels. Our research includes the biological determinants that allow disseminated cancer cells to gain a foothold in foreign tissue microenvironments, where they can succeed in spawning rapidly growing metastatic colonies.

Ludwig Center at MIT
77 Massachusetts Avenue, 76-158
Cambridge, MA, us, 02139
T 617 258 5159
F 617 258 5213

Directors

Robert A. Weinberg

I’ve written or edited five books and more than 390 articles. My three most recent books, intended for a lay audience, are One Renegade Cell, Racing to the Beginning of the Road: The Search for the Origin of Cancer and Genes and the Biology of Cancer, co-written with Dr. Harold E. Varmus, former Director of the National Institutes of Health. I recently published the second edition of my widely used textbook The Biology of Cancer.

Born in Pittsburgh in 1942, I received my BS (1964) and PhD (1969) in Biology from MIT and performed postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California. I returned to MIT in 1972.

TEAM

Frank
Gertler
M.I.T. Center
Bio

My laboratory studies how contextual signals are integrated by intracellular signaling pathways to orchestrate directed cell movement and thus tumor cell invasion. One important research area focuses on Mena, a molecule that regulates actin polymerization and cell:matrix/cell:cell adhesion. Changes in alternative splicing of the Mena mRNA during the epithelial-to-mesenchymal transition and during tumor progression produce distinct Mena protein isoforms with significantly different functions. In primary carcinomas, an epithelial-specific Mena isoform enhances cell:cell adhesion and suppresses invasion and metastasis. However, as tumors progress to malignancy another change alternative splicing produces an invasion-specific Mena isoform that promotes cell motility and chemotaxis, exerting a potent pro-metastatic effect on carcinoma cells. Fascinated by the divergent functions conferred to Mena by alternative splicing, we also are investigating the role of alternative splicing in metastatic progression.

Education
PhD, University of Wisconsin, Madison, 1992

Richard O.
Hynes
M.I.T. Center
Bio

My research has focused on the cytoskeleton and the extracellular matrix and led to the discovery of fibronectin, vimentin and osteopontin. We first demonstrated a physical link between fibronectin in the ECM and the actin cytoskeleton, which led to the discovery of integrins. My laboratory undertook a screen to discover metastasis-promoting genes, which led to the discovery of the RhoC protein as a key driver of metastasis. Our research in this area has continued to focus on identifying drivers of metastasis in melanoma, prostate and breast cancer cells. We have applied the use of proteomics to define the entire census of proteins that compose the ECM formed in primary tumors and derived metastases, with the goal of defining ECM components that facilitate metastasis and serve as useful diagnostic or prognostic markers of tumor progression.

Education
PhD, Massachusetts Institute of Technology, 1971

Jacqueline A.
Lees
M.I.T. Center
Bio

My group is investigating the mechanisms that influence the progression and metastasis of mesenchymal tumors, i.e., sarcomas. We wish to learn how the mesenchymal nature of these tumors relates to the mesenchymal state of carcinoma cells that have undergone an epithelial-to-mesenchymal transition (EMT). Our studies use cell lines derived from a mouse model of metastatic osteosarcoma (OS) and have shown that co-injection of primary wild-type mesenchymal stromal cells (MSCs) promotes the ability of primary OS tumor cells to form subcutaneous tumors and enables the formation of metastases by these tumors. Our experiments are directed toward identifying the MSC-induced signals and how they correlate with the tumor-initiating powers of sarcoma cells and whether these mechanisms are broadly applicable to other mesenchymal tumor types.

Education
PhD, University College, University of London, UK, 1990

Michael
Hemann
M.I.T. Center
Bio

My laboratory is focused on understanding how nests of tumor cells, termed Minimal Residual Disease, or MRD, can survive for a sustained period of time in a dormant state after chemotherapy. Our work has led to the identification of specific tissue microenvironments that promote the survival of tumor cells after treatment. By understanding how these anatomical sites protect cancer cells, we have been able to develop strategies to resensitize tumors to front-line chemotherapy. Importantly, metastatic disease shows many of the characteristics of MRD. Hence, our work should lead to novel strategies to sensitize drug-resistant metastatic cells to existing therapies.

Education
PhD, Johns Hopkins University, 2001

Tyler
Jacks
M.I.T. Center
Bio

My laboratory has employed gene-targeting technology to create mouse models of human lung cancer to study tumor progression and metastasis. Our gene-expression analyses of primary lung tumors, metastases and cell lines have uncovered a metastasis-associated gene expression signature. Integration of these datasets with human tumor data are providing insights into the underlying mechanisms of metastasis. Several tumors and cell lines from these models have been subjected by us to whole-exome and whole-genome DNA sequencing as well. These data are providing us with an increasingly complete view of tumor evolution leading to metastatic dissemination in these model systems and in human lung cancer.

Education
PhD, University of California, San Francisco, 1988

PUBLICATIONS

Chaffer, C.L., Marjanovic, N.D., Lee, T., Bell, G., Kleer, C.G., Reinhardt, F., D’Alessio, A.C., Young, R.A., Weinberg, R.A. (2013). Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell  154:311-324.

Scheel, C., Chaffer, C.L,. Eaton, E. N., Hsin-Jung, L., Kah, K.J., Birie, B., Reinhardt, F., and Weinberg, R.A.  An autocrine signaling context necessary for tumorigenicity and metastasis of breast cancer. Cell 145:926-940.

Guo, W., Keckesova, Z., Liu Donaher, J., Shibue, T., Tischler, V., Reinhardt, F., Itzkovitz, S., Noske, A., Zürrer-Härdi, U., Bell, G., Tam, W.L., Mani, S.A., van Oudenaarden, A., and Weinberg, R.A.  (2011). Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State. Cell 148:1015-1028.

Gupton, S.L., Riquelme, D., Hughes-Alford, S.K., Tadros, J., Rudina, S.S., O Hynes, R., Lauffenburger, D., and Gertler, F.B. (2012). Mena binds α5 integrin directly and modulates α5β1 function. The Journal of Cell Biology 198, 657–676.

Shapiro, I.M., Cheng, A.W., Flytzanis, N.C., Balsamo, M., Condeelis, J.S., Oktay, M.H., Burge, C.B., and Gertler, F.B. (2011). An EMT-Driven Alternative Splicing Program Occurs in Human Breast Cancer and Modulates Cellular Phenotype. PLoS Genet. 7, e1002218.

Philippar, U., Roussos, E.T., Oser, M., Yamaguchi, H., Kim, H.-D., Giampieri, S., Wang, Y., Goswami, S., Wyckoff, J.B., Lauffenburger, D.A., et al. (2008). A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Developmental Cell 15, 813–828.

Luke Gilbert and Michael Hemann. Context-specific roles for paracrine IL-6 in lymphomagenesis. Genes & Dev. (2012) 26(15):1758-68.

Justin Pritchard, Luke Gilbert, Corbin Meacham, Jennifer Ricks, Hai Jiang, Douglas Lauffenburger, and Michael Hemann. BCL-2 family genetic profiling reveals microenvironment-specific determinants of therapeutic response. Cancer Research (2011) 71(17):5850-5858

Luke Gilbert and Michael Hemann. DNA damage mediated induction of a chemoresistant niche. Cell (2010) 143:1-12.

Labelle, M., Begum, S. and Hynes, R.O. (2011). Direct Signaling Between Platelets and Cancer Cells Induces an EMT-Like Transition and Promotes Metastasis.  Cancer Cell 20: 576-590.

Naba, A., Clauser, K.R., Hoersch, S., Liu, H., Carr, S.A. and Hynes, R.O. (2012). The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol. Cell Proteomics. 11(4): M111.014647.

Lamar, JM, Stern, P., Liu, H., Schindler, JW, Jiang, Z. and Hynes, RO. (2012). The Hippo pathway target, YAP, promotes metastasis through its TEAD interaction domain. Proc Natl Acad Sci USA. 109: E2441-2450.

Winslow MM, Dayton TL, Rerhaak RG, Kim-Kiselak C, Snyder EL, Feldser DM, Hubbard DD, DuPage M, Whittaker CA, Hoersch S,  Yoon S, Crowley D, Bronson RT, Chiang DY, Meyerson M, Jacks T. 2011. Suppression of Lung Adenocarcinoma Progression by Nkx2-1. Nature 473(7345): 101-104.

Snyder EL, Watanabe H, Magendantz M, Hoersch S, Chen TA, Wang DG, Crowley D, Whittaker CA, Meyerson M, Kimura S, Jacks T 2013. Nkx2-1 represses a latent gastric differentiation program in lung adenocarcinoma. Mol. Cell 50(2): 185-199.

Li C, Chen G, Dayton TL, Kim-Kiselak C, Hoersch S, Whittaker CA, Bronson RT, Beer D, Winslow MW and Jacks T. Differential Tks5 isoform expression contributes to metastatic invasion of lung adenocarcinoma. 2013. Genes Dev. 27: 1557-1567.

Arvind Ravi, Allan M. Gurtan, Madhu S. Kumar, Arjun Bhutkar, Christine Chin, Victoria Lu, Jacqueline A. Lees, Tyler Jacks, Phillip A. Sharp (2012). Proliferation and tumorigenesis of a murine sarcoma cell line I the absence of DICER1. Cancer Cell 21: 848–855.

Zhang, G.J., Hoersch, S., Amsterdam, A., Whitaker, C., Lees, JA., Hopkins, N. (2010). Highly aneuploid zebrafish malignant peripheral nerve sheath tumors have genetic alterations similar to human cancers. Proc. Natl. Acad. Sci. USA 107:16940-16945.

Seth D. Berman, Eliezer Calo, Allison S. Landman, Paul S. Danielian, Emily S. Miller, Julie C. West, Borel Djouedjong Fonhoue, Alicia Caron, Roderick Bronson, Mary L. Bouxsein, Siddhartha Mukherjee and Jacqueline A. Lees. (2008). Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci USA. 105: 11851–11856.