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, 2028 - Immune-driven Airway Epithelial Dysfunction in Muco-obstructive Asthma , Co-Investigator . Sponsor: NIH, 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
  • September 23, 2011 - July 31, 2017 - Leukocyte Biomarkers for Predicting Human Breast Cancer Outcomes , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U54CA163123
  • January 1, 2015 - December 31, 2016 - CUTTING EDGE LINEAGE TRACKING OF TUMOR-EDUCATED IMMUNE CELLS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA191428
  • January 1, 2012 - December 31, 2016 - Epithelial Progenitor Cells in Lung Repair and Regeneration , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01HL111054
  • July 1, 1979 - March 31, 2016 - Evolving Microenvironments in Airway Inflammation , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01HL024136
  • September 1, 2009 - August 31, 2014 - Collaborative Innate-Adaptive Immune Regulation of Tumor Progression , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA141451
  • May 1, 2012 - April 30, 2014 - Defining the First Hours of Lung metastasis using Intravital Live-Imaging , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA167601
  • June 5, 2011 - June 4, 2013 - Multiphoton Instrumentation for Translational Assays from Human Tissue Biopsies , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10RR029266
  • July 17, 2009 - June 30, 2011 - Regulation of T cell Functions by the Breast Cancer Microenvironment , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA134622
  • April 1, 2008 - March 31, 2010 - New Models for Molecular-Level Imaging of Cell Signaling in vivo. , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21RR024895
  • March 1, 2005 - February 28, 2008 - Imaging-Based Analysis of Tolerance-Induction Mechanisms , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI062899
  • March 21, 1998 - October 14, 2000 - GENES ASSOCIATED WITH POSTTHYMIC T CELL DIFFERENTIATION , Principal Investigator . Sponsor: NIH, Sponsor Award ID: F32AI010120

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. Courau T, Jaszczak RG, Samad B, Flynn E, Chew NW, Reeder GC, Tsui J, Teklu S, Pass LF, Edwards AW, Naser M, Ray A, Wismer H, Bunis D, Lupin-Jimenez L, Gavil NV, Masopust D, Graham JP, Skelly DA, Vesco X, Liu ET, Fragiadakis GK, Combes AJ, Krummel MF. Differential assembly of mouse and human tumor microenvironments. Nat Immunol. 2026 Jun; 27(6):1282-1293. View on PubMed
  2. Fan AC, Thota RR, Serwas N, Vykunta VS, Marchuk K, Ruhland MK, Liu L, Johnson G, Edwards A, Krummel MF. Submicrometre sampling of living cells by macrophages. Nature. 2026 Jun; 654(8118):495-503. View on PubMed
  3. Tristan Courau, View ORCID ProfileRebecca G. Jaszczak, Bushra Samad, Emily Flynn, Nayvin W. Chew, Gabriella C. Reeder, Jessica Tsui, Arja Ray, Harrison Wismer, Daniel Bunis, Leonard Lupin-Jimenez, Noah V. Gavil, David Masopust, John P. Graham, Daniel A. Skelly, Xavier Vesco, Edison T. Liu, Gabriela K. Fragiadakis, Alexis J. Combes, Matthew F. Krummel. Differential Assembly of Mouse and Human Tumor Microenvironments. Nature Immunology. 2026. View on PubMed
  4. Kuhn NF, Zaleta-Linares I, Hu KH, Courau T, Davidson B, Tam T, Chu CW, Kinet MJ, Rosenblum MD, Combes AJ, Nyberg WA, Eyquem J, Krummel MF. Local gene editing of fibroblasts in tumors reveals a new cancer-associated fibroblast state. J Exp Med. 2026 May 04; 223(5). View on PubMed
  5. Fan AC, Thota R, Serwas N, Vykunta VS, Marchuk K, Ruhland MK, Liu L, Johnson G, Edwards A, Krummel MF. Submicron-Sampling of Living Cells by Macrophages. bioRxiv. 2025 Dec 02. View on PubMed
  6. Sarma A, Christenson SA, Shoshana BZ, Oliveira AP, Neyton LPA, Mick E, Sinha P, Wilson JG, Moazed F, Leligdowicz A, Maddali MV, Siegel ER, Lyon ZM, Carrillo SH, Zhou H, Jauregui A, Ghale R, Caldera S, Hayakawa PS, Deiss T, Love C, Byrne A, Kalantar KL, DeRisi JL, Erle DJ, Krummel MF, Kangelaris KN, Hendrickson CM, Woodruff PG, Matthay MA, Bos LDJ, Langelier CR, Calfee CS, COMET Consortium. Acute Respiratory Distress Syndrome Molecular Phenotypes Have Distinct Lower Respiratory Tract Transcriptomes. Am J Respir Crit Care Med. 2025 Dec; 211(12):2352-2362. View on PubMed
  7. Narendra R, Lydon EC, Phan HV, Spottiswoode N, Neyton LP, Diray-Arce J, IMPACC Network, COMET Consortium, EARLI Consortium, Becker PM, Kim-Schulze S, Hoch A, Pickering H, van Zalm P, Cairns CB, Altman MC, Augustine AD, Bosinger S, Eckalbar W, Guan L, Doni Jayavelu N, Kleinstein SH, Krammer F, Maecker HT, Ozonoff A, Peters B, Rouphael N, Montgomery RR, Reed E, Schaenman J, Steen H, Levy O, Haller SC, Erle D, Hendrickson CM, Krummel MF, Matthay MA, Woodruff P, Haddad EK, Calfee CS, Langelier CR. Minimalistic transcriptomic signatures permit accurate early prediction of COVID-19 mortality. JCI Insight. 2025 Nov 10; 10(21). View on PubMed
  8. Pass L, Krummel MF. Dendritic Cells at the Center of Reactive Tumor Immunity. Immunol Rev. 2025 Nov; 336(1):e70072. View on PubMed
  9. LaHue SC, Takegami N, Simmasalam R, Baqai A, Munoz E, Sikri A, de Courson TDB, Singhal NS, Eckalbar W, Langelier CR, Hendrickson CM, Calfee CS, Erle DJ, Krummel MF, Woodruff PG, Oskotsky T, Sirota M, Ferguson A, Douglas VC, Newman JC, Pleasure SJ, Wilson MR, Singhal NS. Delirium in hospitalized COVID-19 patients is associated with dynamic changes in peripheral immune gene expression. Geroscience. 2026 Jun; 48(3):4209-4223. View on PubMed
  10. Courau T, Desai A, Wagner A, Combes AJ, Krummel MF. The coming era of nudge drugs for cancer. Cancer Cell. 2025 Nov 10; 43(11):1973-1979. View on PubMed
  11. Kuhn NF, Zaleta-Linares I, Hu KH, Courau T, Davidson B, Tam T, Combes AJ, Nyberg WA, Eyquem J, Krummel MF. Discovery of a Linked Constellation of Gene Expression Revealed by Local Editing of Fibroblasts in Tumors. bioRxiv. 2025 Aug 26. View on PubMed
  12. Ray A, Bassette M, Hu KH, Pass LF, Courau T, Samad B, Combes AJ, Johri V, Davidson B, Wai K, Ha P, Hernandez G, Zaleta-Linares I, Krummel MF. Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors. Sci Immunol. 2025 07 11; 10(109):eadt3537. View on PubMed
  13. Jayavelu ND, Qi J, Milliren CE, Ozonoff A, Liu S, Levy O, Baden LR, Melamed E, McComsey GA, Cairns CB, Schaenman J, Shaw AC, Hafler DA, Corry DB, Kheradmand F, Atkinson MA, Brakenridge SC, Agudelo Higuita NI, Metcalf JP, Hough CL, Messer WB, Pulendran B, Nadeau KC, Davis MM, Geng LN, Sesma AF, Simon V, Krammer F, Bime C, Calfee CS, Bosinger SE, Eckalbar W, Steen H, Maecker HT, IMPACC Network, Augustine AD, Diray-Arce J, Haddad EK, Sekaly RP, Kraft M, Woodruff PG, Erle DJ, Ehrlich LIR, Montgomery RR, Becker PM, Altman MC, Fourati S. Type 2 immune responses are associated with less severe COVID-19 in a hospitalized cohort. J Allergy Clin Immunol Glob. 2025 Nov; 4(4):100515. View on PubMed
  14. Narendra R, Lydon EC, Van Phan H, Spottiswoode N, Neyton LP, Diray-Arce J, IMPACC Network, COMET Consortium, EARLI Consortium, Becker PM, Kim-Schulze S, Hoch A, Pickering H, van Zalm P, Cairns CB, Altman MC, Augustine AD, Bosinger S, Eckalbar W, Guan L, Jayavelu ND, Kleinstein SH, Krammer F, Maecker HT, Ozonoff A, Peters B, Rouphael N, Montgomery RR, Reed E, Schaenman J, Steen H, Levy O, Carillo SA, Erle D, Hendrickson CM, Krummel MF, Matthay MA, Woodruff P, Haddad EK, Calfee CS, Langelier CR. Minimalistic Transcriptomic Signatures Permit Accurate Early Prediction of COVID-19 Mortality. medRxiv. 2025 May 19. View on PubMed
  15. Tanaka M, Lum L, Hu KH, Chaudhary P, Hughes S, Ledezma-Soto C, Samad B, Superville D, Ng K, Chumber A, Benson C, Adams ZN, Kersten K, Aguilar OA, Fong L, Combes AJ, Krummel MF, Reeves MQ. Tumor cell heterogeneity drives spatial organization of the intratumoral immune response. J Exp Med. 2025 Jun 02; 222(6). View on PubMed
  16. LaHue SC, Takegami N, Simmasalam R, Baqai A, Munoz E, Sikri A, de Courson TDB, Singhal NS, Eckalbar W, Langelier CR, Hendrickson CM, Calfee CS, Erle DJ, Krummel MF, Woodruff PG, Oskotsky T, Sirota M, Ferguson A, Douglas VC, Newman JC, Pleasure SJ, Wilson MR, COMET consortium, Singhal NS. Peripheral blood mononuclear cell transcriptomic trajectories reveal dynamic regulation of inflammatory actors in delirium. medRxiv. 2025 Feb 20. View on PubMed
  17. Cleary SJ, Qiu L, Seo Y, Baluk P, Liu D, Serwas NK, Taylor CA, Zhang D, Cyster JG, McDonald DM, Krummel MF, Looney MR. Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer. J Exp Med. 2025 May 05; 222(5). View on PubMed
  18. Ray A, Bassette M, Hu KH, Pass LF, Courau T, Samad B, Combes A, Johri V, Davidson B, Wai K, Ha P, Hernandez G, Zaleta-Linares I, Krummel MF. Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors. bioRxiv. 2025 Feb 16. View on PubMed
  19. Ray A, Hu KH, Kersten K, Courau T, Kuhn NF, Zaleta-Linares I, Samad B, Combes AJ, Krummel MF. Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis. J Exp Med. 2025 Jan 06; 222(1). View on PubMed
  20. Spottiswoode N, Tsitsiklis A, Chu VT, Phan HV, DeVoe C, Love C, Ghale R, Bloomstein J, Zha BS, Maguire CP, Glascock A, Sarma A, Mourani PM, Kalantar KL, Detweiler A, Neff N, Haller SC, COMET Consortium, DeRisi JL, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Matthay MA, Woodruff PG, Calfee CS, Langelier CR. Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia. Nat Commun. 2024 10 29; 15(1):9339. View on PubMed

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