David H. Koch Professor in Science
Professor of Biology and Biological Engineering
Director, MIT Center for Precision Cancer Medicine
Director, KI Clinical Investigator Program
KI Research Areas of Focus:
"The Yaffe laboratory is interested in understanding how signaling pathways are integrated at the molecular and systems levels to control cellular responses. Our interest has particularly focused on signaling pathways and networks that control inflammation and injury, cell cycle progression and DNA damage responses in cancer and cancer therapy."
Professor Yaffe is the David H. Koch Professor of Science and Professor of Biology and Biological Engineering at MIT, where he has been a member of the faculty since 2000; he is also an attending surgeon at the Beth Israel Deaconess Medical Center. Professor Yaffe earned his M.D.-Ph.D. degree from Case Western Reserve University. He then completed a residency in General Surgery at University Hospitals of Cleveland and New England Deaconess Hospital, and a fellowship in Surgical Critical Care, Trauma and Burns at Harvard Medical School's Harvard-Longwood Critical Care Program. He was a post-doctoral fellow with Lewis Cantley in the Department of Cell Biology at Harvard Medical School. Professor Yaffe is the Scientific Editor-in-Chief of Science Signaling, and a member of the Editorial Boards of Molecular & Cellular Proteomics and Cell Cycle. He is a Colonel in the U.S. Army Reserve Medical Corps and a decorated veteran of the war in Afghanistan. Professor Yaffe is a co-founder of Consensus Pharmaceuticals, the DNA Repair Company, On-Q-ity, and Merrimack Pharmaceuticals. He also a co-founder and a member of the scientific advisory board of Applied Biomath and Thrombo Therapeutics.
The Yaffe Lab is interested in understanding how signaling pathways are integrated at the molecular and systems level to control cellular responses. We have a long-standing interest in understanding the relationship between inflammation, cell injury, and cancer, and how this can be used to design better anti-cancer treatments. We have done this focusing on signaling pathways and networks that respond to various types of cell stress and injury in order to control cell cycle progression and DNA damage responses, as well as cross-talk between inflammation, cytokine signaling and cancer. At the most basic molecular level, our work is directed to understanding how modular protein domains and kinases work together to build molecular signaling circuits. At the clinical level, our work translates into what has been called ‘systems pharmacology’ - namely, determining how this cross-talk between pathways can be therapeutically targeted with specific drug combinations to increase the efficacy of cancer treatment, or to improve patient outcomes after tissue trauma. The research is multi-disciplinary and encompasses biochemistry, biophysics, structural and cell biology, engineering, and computation/bioinformatics.
Patterson JC, Joughin BA, Prota AE, Mühlethaler T, Jonas OH, Whitman MA, Varmeh S, Chen S, Balk SP, Steinmetz MO, Lauffenburger DA, Yaffe MB. VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. Cell Syst. 2019 Jul 24;9(1):74-92.e8.
Creixell P, Pandey JP, Palmeri A, Bhattacharyya M, Creixell M, Ranganathan R, Pincus D, Yaffe MB. Hierarchical organization endows the kinase comain with regulatory plasticity. Cell Systems 2018 7:371-383.
Suarez-Lopez L, Sriram G, Kong YW, Morandell S, Merrick KA, Hernandez Y, Haigis KM, Yaffe MB. MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis. Proc Natl Acad Sci USA. 2018 115:E4236-E4244.
Cannell IG, Merrick KA, Morandell S, Zhu CQ, Braun CJ, Grant RA, Cameron ER, Tsao MS, Hemann MT, Yaffe MB. A pleiotropic RNA-binding protein controls distinct cell cycle checkpoints to drive resistance of p53-defective tumors to chemotherapy. Cancer Cell. 2015 28:623-37.
Morandell S, Reinhardt HC, Cannell IG, Kim JS, Ruf DM, Mitra T, Couvillon AD, Jacks T, Yaffe MB. A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response In Vivo. Cell Reports 2013 5:868-77.
Floyd SR, Pacold ME, Huan Q, Clarke SM, Lam FC, Cannell IG, Bryson BD, Rameseder J, Lee MJ, Blake EJ, Fydrych A, Ho R, Greenberger BA, Chen GC, Maffa A, Del Rosario AM, Root DE, Carpenter AE, Hahn WC, Sabatini DM, Chen CC, White FM, Bradner JE, Yaffe MB. The bromodomain protein Brd4 insulates chromatin from DNA damage signaling. Nature 2013 498:246-250.
Lee MJ, Ye AS, Gardino AK, Heijink AM, Sorger PK, MacBeath G, Yaffe MB. Sequential application of anti-cancer drugs enhances cell death by re-wiring apoptotic signaling networks. Cell 2012 149:780-94.
Manke IA, Lowery DM, Nguyen A, Yaffe MB. BRCT repeats as phosphopeptide binding modules involved in protein targeting. Science 2003 302:636-639.
Janes KA, Albeck JG, Gaudet S, Sorger PK, Lauffenburger DA, Yaffe MB. A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis. Science. 2005 310:1646-53.
Elia AE, Cantley LC, Yaffe MB. Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 2003 299:1228-31