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.

Research Funding

  • April 1, 2008 - March 31, 2023 - Understanding Asthma Endotypes, Co-Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: U19AI077439
  • June 15, 2015 - May 31, 2020 - Manipulating collectivity and Niches for Developing CD8 Immunity, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01AI114787
  • September 1, 2015 - August 31, 2018 - Living Tumor Biopsies to Interrogate Immune Function and Response to Therapy, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R21CA196468
  • September 15, 2002 - December 31, 2017 - Cytoskeletal Regulation of T cell Motility and Synaptic Signaling, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01AI052116

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. Seed RI, Kobayashi K, Ito S, Takasaka N, Cormier A, Jespersen JM, Publicover J, Trilok S, Combes AJ, Chew NW, Chapman J, Krummel MF, Lou J, Marks J, Cheng Y, Baron JL, Nishimura SL A tumor-specific mechanism of Treg enrichment mediated by the integrin αvβ8.  View on PubMed
  2. Learned adaptive multiphoton illumination microscopy for large-scale immune response imaging.  View on PubMed
  3. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Voyer TL, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, UCSF COMET consortium , Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19.  View on PubMed
  4. Chan V, Gherardini PF, Krummel MF, Fragiadakis GK A "data sharing trust" model for rapid, collaborative science.  View on PubMed
  5. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Chew NW, Cleary SJ, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Im KW, Serwas NK, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, UCSF COMET Consortium , Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF Global absence and targeting of protective immune states in severe COVID-19.  View on PubMed
  6. Sarma A, Christenson S, Mick E, Deiss T, DeVoe C, Pisco A, Ghale R, Jauregui A, Byrne A, Moazed F, Spottiswoode N, Sinha P, Zha B, Neff N, Tan M, Serpa PH, Ansel KM, Wilson J, Leligdowicz A, Seigel E, Sirota M, DeRisi J, Matthay M, Consortium C, Hendrickson C, Kangelaris K, Krummel M, Woodruff P, Erle D, Calfee C, Langelier C COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone.  View on PubMed
  7. Krummel M, Hu K, de Vries EGE, Goetz JG, Passaro D, Subramaniam S, Misteli T, Skala M, Bravo-Cordero JJ, Sutcliffe JL Visualizing Cancer.  View on PubMed
  8. Argüello RJ, Combes AJ, Char R, Gigan JP, Baaziz AI, Bousiquot E, Camosseto V, Samad B, Tsui J, Yan P, Boissonneau S, Figarella-Branger D, Gatti E, Tabouret E, Krummel MF, Pierre P SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution.  View on PubMed
  9. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF Global Absence and Targeting of Protective Immune States in Severe COVID-19.  View on PubMed
  10. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF Global Absence and Targeting of Protective Immune States in Severe COVID-19.  View on PubMed
  11. Freedman TS, Headley MB, Serwas N, Ruhland M, Castellanos CA, Combes AJ, Krummel MF Lessons of COVID-19: A roadmap for post-pandemic science.  View on PubMed
  12. Bald T, Krummel MF, Smyth MJ, Barry KC The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. 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.  View on PubMed
  16. Tang S, Cannon J, Yang K, Krummel MF, Baker JR, Choi SK Spacer-Mediated Control of Coumarin Uncaging for Photocaged Thymidine.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

Go to UCSF Profiles, powered by CTSI