Matthew F. Krummel, PhD

Matthew F. Krummel, PhD

Associate Professor, Department of Pathology, UCSF

Phone: (415) 514-3130 (voice)
Box 0511, UCSF
San Francisco, CA 94143-0511

View on UCSF Profiles

Cancer Center Membership

Program Member » Cancer, Immunity, and Microenvironment

Research Summary

Important discoveries come from fundamental research and ‘How does this work’ questions. For the past 15 years, I have studied mechanisms that regulate T cell responses and therefore regulate immune function, using cutting-edge real-time imaging methods to ask these kinds of questions. As a graduate student, I developed expertise in the generation and use of monoclonal antibodies targeted to costimulatory and inhibitory molecules on T cells. One of these projects developed antibodies to CTLA-4, which not only identified an inhibitory pathway of T cell regulation but also could be used to trigger or block that pathway. I subsequently applied these antibodies toward upregulating T cell responses to antigens in vivo and then toward augmenting immune responses to tumors. That approach led to the development of human antibodies of the same type, a therapy now named ipilimumab, and progressing toward FDA approval for treatment of melanoma and other cancers. I am firmly convinced that there is considerably more to be done with respect to modulating signaling in tumor microenvironments.
My lab now focuses on figuring out how immune systems—collections of cells in complex tissues—work. Our work capitalizes on using fluorescent proteins to track information processing by the immune system using imaging and/or flow cytometry. This has frequently taken the form of tagging and modulating components of the T cell receptor complex to understand the dynamics of signaling, as well as tagging and modulating motor proteins and other cytoskeletal proteins to study how these dynamics are controlled. These approaches have profited from considerable investments in developing novel imaging approaches. In addition, my lab emphasizes the use of fluorescent imaging approaches to understand how information is exchanged in the dense cellular milieu of organs.
We have developed imaging approaches to allow us to track T lymphocytes in lymph nodes, pancreas, lungs, and tumors. These are revealing unexpected dynamics of the assembly of complexes of lymphocytes and are paving the way to the types of studies defined herein—where key lymphocytes and stromal components begin again to be targeted with antibodies to disrupt interactions that likely control the local response. One exceptionally useful approach that we’ve developed is the generation of spontaneous models of breast cancer in which the stromal cells that interact with tumors become fluorescent by virtue of the uptake of very stable fluorescent protein variants. This enables us to focus on specific phagocytes in the tumor microenvironments and begin to characterize them as primary players in transmitting signals to lymphocytes and regulating disease outcome.
We continue to seek ways to understand basic biology and then facile means to translate that understanding into mechanisms for improving selectivity in the immune response.


University of Illinois at Champaign-Urbana, B.S.+B.S., 1985-1989, Biology and Chemistry
University of California at Berkeley, Ph.D., 1989-1995, Immunology
Walter and Eliza Hall Institute, Melbourne Aus., 1996-1997, Immunology
Stanford University, 1997-2001, Immunology

Professional Experience

  • Summer 1987
    Summer Undergraduate Research Fellow. University of Texas Health Science Center at Dallas
  • Summer 1988
    Stagiare (Technician) Institut Pasteur, Paris, Unite de Genie Micro-Biologique
  • Aug 1989-May 1995
    Graduate Student, University of California at Berkeley, Department of Molecular and Cell Biology
  • June 1995-May 1996
    Postdoctoral Fellow, University of California at Berkeley
  • Aug 1996-Sept 1997
    Postdoctoral Fellow, Walter and Eliza Hall Institute of Medical Research, Melbourne Australia
  • Nov 1997-August 2001
    Postdoctoral Fellow, Beckman Institute, Stanford University, Stanford, CA
  • August 2001-2006
    Assistant Professor, Department of Pathology, University of California at San Francisco
  • July 2006-present
    Associate Professor, Department of Pathology, University of California at San Francisco

Honors & Awards

  • 1986
    University of Illinois: James Scholar
  • 1996-1997
    Postdoctoral Fellowship, Juvenile Diabetes Foundation International
  • 1997-2000
    NRSA Postdoctoral Fellowship, National Institutes of Health
  • 2004-2007
    Investigator Award, Cancer Research Institute

Selected Publications

  1. Krummel MF, Friedman RS, Jacobelli J. Modes and mechanisms of T cell motility: roles for confinement and Myosin-IIA. Curr Opin Cell Biol. 2014 Oct; 30:9-16.
    View on PubMed
  2. Krummel MF. Illuminating emergent activity in the immune system by real-time imaging. Nat Immunol. 2010 Jul; 11(7):554-7.
    View on PubMed
  3. Krummel MF, Cahalan MD. The immunological synapse: a dynamic platform for local signaling. J Clin Immunol. 2010 May; 30(3):364-72.
    View on PubMed
  4. Krummel MF. Immunological synapses: breaking up may be good to do. Cell. 2007 May 18; 129(4):653-5.
    View on PubMed
  5. Krummel MF, Macara I. Maintenance and modulation of T cell polarity. Nat Immunol. 2006 Nov; 7(11):1143-9.
    View on PubMed

Go to UCSF Profiles, powered by CTSI