University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Matthew F. Krummel, PhD

Matthew F. Krummel, PhD

Professor, Department of Pathology, UCSF
Robert E. Smith Endowed Chair in Experimental Pathology, UCSF

Cancer Center Program Memberships

Cancer Immunology

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.

Education

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

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. Freedman TS, Headley MB, Serwas N, Ruhland M, Castellanos CA, Combes AJ, Krummel MF. Lessons of COVID-19: A roadmap for post-pandemic science. J Exp Med. 2020 09 07; 217(9).
    View on PubMed
  2. Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat Immunol. 2020 Aug; 21(8):835-847.
    View on PubMed
  3. Hu KH, Eichorst JP, McGinnis CS, Patterson DM, Chow ED, Kersten K, Jameson SC, Gartner ZJ, Rao AA, Krummel MF. ZipSeq: barcoding for real-time mapping of single cell transcriptomes. Nat Methods. 2020 Aug; 17(8):833-843.
    View on PubMed
  4. Ruhland MK, Roberts EW, Cai E, Mujal AM, Marchuk K, Beppler C, Nam D, Serwas NK, Binnewies M, Krummel MF. Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells. Cancer Cell. 2020 Jun 08; 37(6):786-799.e5.
    View on PubMed
  5. Levine LS, Mahuron KM, Tsai KK, Wu C, Mattis DM, Pauli ML, Oglesby A, Lee JC, Spitzer MH, Krummel MF, Algazi AP, Rosenblum MD, Alvarado M, Daud AI. Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma. Ann Surg Oncol. 2020 Jun 02.
    View on PubMed
  6. Tang S, Cannon J, Yang K, Krummel MF, Baker JR, Choi SK. Spacer-Mediated Control of Coumarin Uncaging for Photocaged Thymidine. J Org Chem. 2020 Mar 06; 85(5):2945-2955.
    View on PubMed
  7. Crotty S, Blish C, Cadwell K, Chi H, Goldrath A, Green D, Kaech SM, Krummel M, Pepper M, Rothlin CV, Wherry EJ. Reinvigorating NIH Grant Peer Review. Immunity. 2020 01 14; 52(1):1-3.
    View on PubMed
  8. Thumkeo D, Katsura Y, Nishimura Y, Kanchanawong P, Tohyama K, Ishizaki T, Kitajima S, Takahashi C, Hirata T, Watanabe N, Krummel MF, Narumiya S. mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse. Sci Adv. 2020 01; 6(1):eaay2432.
    View on PubMed
  9. Lowe MM, Boothby I, Clancy S, Ahn RS, Liao W, Nguyen DN, Schumann K, Marson A, Mahuron KM, Kingsbury GA, Liu Z, Munoz Sandoval P, Rodriguez RS, Pauli ML, Taravati K, Arron ST, Neuhaus IM, Harris HW, Kim EA, Shin US, Krummel MF, Daud A, Scharschmidt TC, Rosenblum MD. Regulatory T cells use arginase 2 to enhance their metabolic fitness in tissues. JCI Insight. 2019 12 19; 4(24).
    View on PubMed
  10. Krummel M, Blish C, Kuhns M, Cadwell K, Oberst A, Goldrath A, Ansel KM, Chi H, O'Connell R, Wherry EJ, Pepper M. Universal Principled Review: A Community-Driven Method to Improve Peer Review. Cell. 2019 Dec 12; 179(7):1441-1445.
    View on PubMed
  11. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020 01; 20(1):7-24.
    View on PubMed
  12. Jahchan NS, Mujal AM, Pollack JL, Binnewies M, Sriram V, Reyno L, Krummel MF. Tuning the Tumor Myeloid Microenvironment to Fight Cancer. Front Immunol. 2019; 10:1611.
    View on PubMed
  13. Puttur F, Denney L, Gregory LG, Vuononvirta J, Oliver R, Entwistle LJ, Walker SA, Headley MB, McGhee EJ, Pease JE, Krummel MF, Carlin LM, Lloyd CM. Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans. Sci Immunol. 2019 06 07; 4(36).
    View on PubMed
  14. Mujal AM, Krummel MF. Immunity as a continuum of archetypes. Science. 2019 04 05; 364(6435):28-29.
    View on PubMed
  15. Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, Tsui J, Ruhland MK, Kersten K, Abushawish MA, Spasic M, Giurintano JP, Chan V, Daud AI, Ha P, Ye CJ, Roberts EW, Krummel MF. Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity. Cell. 2019 04 18; 177(3):556-571.e16.
    View on PubMed
  16. Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. a-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by a-TGFß antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 03 04; 7(1):62.
    View on PubMed
  17. Dahlgren MW, Jones SW, Cautivo KM, Dubinin A, Ortiz-Carpena JF, Farhat S, Yu KS, Lee K, Wang C, Molofsky AV, Tward AD, Krummel MF, Peng T, Molofsky AB. Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches. Immunity. 2019 03 19; 50(3):707-722.e6.
    View on PubMed
  18. Krummel M. Nobel notes value of basic research for new drugs. Nature. 2018 11; 563(7730):184.
    View on PubMed
  19. Krummel MF, Mahale JN, Uhl LFK, Hardison EA, Mujal AM, Mazet JM, Weber RJ, Gartner ZJ, Gérard A. Paracrine costimulation of IFN-? signaling by integrins modulates CD8 T cell differentiation. Proc Natl Acad Sci U S A. 2018 11 06; 115(45):11585-11590.
    View on PubMed
  20. Hung LY, Sen D, Oniskey TK, Katzen J, Cohen NA, Vaughan AE, Nieves W, Urisman A, Beers MF, Krummel MF, Herbert DR. Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism. Mucosal Immunol. 2019 01; 12(1):64-76.
    View on PubMed

Go to UCSF Profiles, powered by CTSI