Max Krummel, PhD

Professor
Department of Pathology
+1 415 514-3130

Our work focuses on understanding patterns of immune cell-cell interactions and how these generate “the immune system”. Our studies of the immune synapse have shown how T cells regulate their motility, how they signal through synapses while moving, how they communicate with each other during arrest, and how they ‘search’ a new tissue. These are all fundamental findings and provide a lens through which we understand T cell function.

Over the past four years, we have developed novel methods and computational platforms to understand immunological processes in space and in time within normal and diseased organs. We were the first to live-image events in progressive tumors in which incoming tumor-specific T cells are captured by a population of myeloid cells. I am tremendously excited that we have begun to develop a pipeline of next-generation protein immuno-therapeutics using imaging to ‘guide’ this development.

Concurrently, we co-developed a  imaging technologies that allow, for the first time, observation of the immune system in the homeostatic, infected/injured, allergic or metastatic lung. As with primary tumors, this latter focus has allowed us to dismiss many hypothetical immune scenarios and intensely study those that define the biology in situ. 

These studies define how the immune system is organizing over space and time and guides novel therapeutic solutions.

Research Summary: 
The Immune Response in 4 Dimensions

Websites

Publications: 

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Immunity

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

Paracrine costimulation of IFN-? signaling by integrins modulates CD8 T cell differentiation.

Proceedings of the National Academy of Sciences of the United States of America

Krummel MF, Mahale JN, Uhl LFK, Hardison EA, Mujal AM, Mazet JM, Weber RJ, Gartner ZJ, Gérard A

Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism.

Mucosal immunology

Hung LY, Sen D, Oniskey TK, Katzen J, Cohen NA, Vaughan AE, Nieves W, Urisman A, Beers MF, Krummel MF, Herbert DR

A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.

Nature medicine

Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD, Alvarado MD, Wolf DM, Bogunovic D, Bhardwaj N, Daud AI, Ha PK, Ryan WR, Pollack JL, Samad B, Asthana S, Chan V, Krummel MF

Subcellular Localization of Antigen in Keratinocytes Dictates Delivery of CD4+ T-cell Help for the CTL Response upon Therapeutic DNA Vaccination into the Skin.

Cancer immunology research

Babala N, Bovens A, de Vries E, Iglesias-Guimarais V, Ahrends T, Krummel MF, Borst J, Bins AD

Understanding the tumor immune microenvironment (TIME) for effective therapy.

Nature medicine

Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC, Vonderheide RH, Pittet MJ, Jain RK, Zou W, Howcroft TK, Woodhouse EC, Weinberg RA, Krummel MF

Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles in Hematopoietic and Nonhematopoietic Cells.

The American journal of pathology

Hung LY, Oniskey TK, Sen D, Krummel MF, Vaughan AE, Cohen NA, Herbert DR

TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer.

Cancer cell

de Mingo Pulido Á, Gardner A, Hiebler S, Soliman H, Rugo HS, Krummel MF, Coussens LM, Ruffell B

Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy.

JCI insight

Loo K, Tsai KK, Mahuron K, Liu J, Pauli ML, Sandoval PM, Nosrati A, Lee J, Chen L, Hwang J, Levine LS, Krummel MF, Algazi AP, Pampaloni M, Alvarado MD, Rosenblum MD, Daud AI

Visualizing dynamic microvillar search and stabilization during ligand detection by T cells.

Science (New York, N.Y.)

Cai E, Marchuk K, Beemiller P, Beppler C, Rubashkin MG, Weaver VM, Gérard A, Liu TL, Chen BC, Betzig E, Bartumeus F, Krummel MF

The Lung is a Host Defense Niche for Immediate Neutrophil-Mediated Vascular Protection.

Science immunology

Yipp BG, Kim JH, Lima R, Zbytnuik LD, Petri B, Swanlund N, Ho M, Szeto VG, Tak T, Koenderman L, Pickkers P, Tool ATJ, Kuijpers TW, van den Berg TK, Looney MR, Krummel MF, Kubes P

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.

Cancer immunology research

Tumeh PC, Hellmann MD, Hamid O, Tsai KK, Loo KL, Gubens MA, Rosenblum M, Harview CL, Taube JM, Handley N, Khurana N, Nosrati A, Krummel MF, Tucker A, Sosa EV, Sanchez PJ, Banayan N, Osorio JC, Nguyen-Kim DL, Chang J, Shintaku IP, Boasberg PD, Taylor EJ, Munster PN, Algazi AP, Chmielowski B, Dummer R, Grogan TR, Elashoff D, Hwang J, Goldinger SM, Garon EB, Pierce RH, Daud A

The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors.

Nature

Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, Thornton EE, Headley MB, David T, Coughlin SR, Krummel MF, Leavitt AD, Passegué E, Looney MR

Control of an Unusual Photo-Claisen Rearrangement in Coumarin Caged Tamoxifen through an Extended Spacer.

ACS chemical biology

Wong PT, Roberts EW, Tang S, Mukherjee J, Cannon J, Nip AJ, Corbin K, Krummel MF, Choi SK

Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment.

The Journal of clinical investigation

Starobinets H, Ye J, Broz M, Barry K, Goldsmith J, Marsh T, Rostker F, Krummel M, Debnath J

Tracking the Spatial and Functional Gradient of Monocyte-To-Macrophage Differentiation in Inflamed Lung.

PloS one

Sen D, Jones SM, Oswald EM, Pinkard H, Corbin K, Krummel MF

CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.

The Journal of experimental medicine

Chong SZ, Evrard M, Devi S, Chen J, Lim JY, See P, Zhang Y, Adrover JM, Lee B, Tan L, Li JL, Liong KH, Phua C, Balachander A, Boey A, Liebl D, Tan SM, Chan JK, Balabanian K, Harris JE, Bianchini M, Weber C, Duchene J, Lum J, Poidinger M, Chen Q, Rénia L, Wang CI, Larbi A, Randolph GJ, Weninger W, Looney MR, Krummel MF, Biswas SK, Ginhoux F, Hidalgo A, Bachelerie F, Ng LG

Micro-Magellan: open-source, sample-adaptive, acquisition software for optical microscopy.

Nature methods

Pinkard H, Stuurman N, Corbin K, Vale R, Krummel MF

CCR2 Influences T Regulatory Cell Migration to Tumors and Serves as a Biomarker of Cyclophosphamide Sensitivity.

Cancer research

Loyher PL, Rochefort J, Baudesson de Chanville C, Hamon P, Lescaille G, Bertolus C, Guillot-Delost M, Krummel MF, Lemoine FM, Combadière C, Boissonnas A

Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma.

The Journal of clinical investigation

Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD

Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.

Cancer cell

Roberts EW, Broz ML, Binnewies M, Headley MB, Nelson AE, Wolf DM, Kaisho T, Bogunovic D, Bhardwaj N, Krummel MF

Visualization of immediate immune responses to pioneer metastatic cells in the lung.

Nature

Headley MB, Bins A, Nip A, Roberts EW, Looney MR, Gerard A, Krummel MF

T cell migration, search strategies and mechanisms.

Nature reviews. Immunology

Krummel MF, Bartumeus F, Gérard A

STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis.

Cancer research

Jones LM, Broz ML, Ranger JJ, Ozcelik J, Ahn R, Zuo D, Ursini-Siegel J, Hallett MT, Krummel M, Muller WJ

A septin requirement differentiates autonomous and contact-facilitated T cell proliferation.

Nature immunology

Mujal AM, Gilden JK, Gérard A, Kinoshita M, Krummel MF

Adaptive Immune Regulation of Mammary Postnatal Organogenesis.

Developmental cell

Plaks V, Boldajipour B, Linnemann JR, Nguyen NH, Kersten K, Wolf Y, Casbon AJ, Kong N, van den Bijgaart RJ, Sheppard D, Melton AC, Krummel MF, Werb Z

TGF-ß-Dependent Dendritic Cell Chemokinesis in Murine Models of Airway Disease.

Journal of immunology (Baltimore, Md. : 1950)

Hashimoto M, Yanagisawa H, Minagawa S, Sen D, Ma R, Murray LA, Tsui P, Lou J, Marks JD, Baron JL, Krummel MF, Nishimura SL

Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice.

PloS one

Bose O, Baluk P, Looney MR, Cheng LE, McDonald DM, Caughey GH, Krummel MF

A critical role for dendritic cells in the evolution of IL-1ß-mediated murine airway disease.

Journal of immunology (Baltimore, Md. : 1950)

Hashimoto M, Yanagisawa H, Minagawa S, Sen D, Goodsell A, Ma R, Moermans C, McKnelly KJ, Baron JL, Krummel MF, Nishimura SL

The subtle hands of self-reactivity in peripheral T cells.

Nature immunology

Mujal AM, Krummel M

Antigen recognition in the islets changes with progression of autoimmune islet infiltration.

Journal of immunology (Baltimore, Md. : 1950)

Lindsay RS, Corbin K, Mahne A, Levitt BE, Gebert MJ, Wigton EJ, Bradley BJ, Haskins K, Jacobelli J, Tang Q, Krummel MF, Friedman RS

Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity.

Cancer cell

Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF

Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.

Cancer cell

Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF

Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function.

Cell stem cell

Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, Rock J, Snitow M, Krummel M, Stripp BR, Vu T, White ES, Whitsett JA, Morrisey EE

Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g.

Cell

Gérard A, Patino-Lopez G, Beemiller P, Nambiar R, Ben-Aissa K, Liu Y, Totah FJ, Tyska MJ, Shaw S, Krummel MF

Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.

PloS one

Li M, Wetzel-Strong SE, Hua X, Tilley SL, Oswald E, Krummel MF, Caron KM

The spatiotemporal cellular dynamics of lung immunity.

Trends in immunology

Lelkes E, Headley MB, Thornton EE, Looney MR, Krummel MF

An evolving autoimmune microenvironment regulates the quality of effector T cell restimulation and function.

Proceedings of the National Academy of Sciences of the United States of America

Friedman RS, Lindsay RS, Lilly JK, Nguyen V, Sorensen CM, Jacobelli J, Krummel MF

Modes and mechanisms of T cell motility: roles for confinement and Myosin-IIA.

Current opinion in cell biology

Krummel MF, Friedman RS, Jacobelli J

Leukotriene B4 amplifies eosinophil accumulation in response to nematodes.

The Journal of experimental medicine

Patnode ML, Bando JK, Krummel MF, Locksley RM, Rosen SD

Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and ?d T cells.

Immunity

Van Dyken SJ, Mohapatra A, Nussbaum JC, Molofsky AB, Thornton EE, Ziegler SF, McKenzie AN, Krummel MF, Liang HE, Locksley RM

Assessing and benchmarking multiphoton microscopes for biologists.

Methods in cell biology

Corbin K, Pinkard H, Peck S, Beemiller P, Krummel MF

Type 2 innate lymphoid cells control eosinophil homeostasis.

Nature

Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, Thornton EE, Krummel MF, Chawla A, Liang HE, Locksley RM

Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells.

Nature immunology

Gérard A, Khan O, Beemiller P, Oswald E, Hu J, Matloubian M, Krummel MF

Perivascular mast cells dynamically probe cutaneous blood vessels to capture immunoglobulin E.

Immunity

Cheng LE, Hartmann K, Roers A, Krummel MF, Locksley RM

Evolving immune circuits are generated by flexible, motile, and sequential immunological synapses.

Immunological reviews

Gérard A, Beemiller P, Friedman RS, Jacobelli J, Krummel MF

Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells.

Journal of immunology (Baltimore, Md. : 1950)

Zhang Y, Chen YC, Krummel MF, Rosen SD

Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung.

The Journal of experimental medicine

Thornton EE, Looney MR, Bose O, Sen D, Sheppard D, Locksley R, Huang X, Krummel MF

Live imaging of the lung.

Current protocols in cytometry

Thornton EE, Krummel MF, Looney MR

Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells.

Cancer cell

Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C, Werb Z, Egeblad M, Krummel MF

The septin cytoskeleton facilitates membrane retraction during motility and blebbing.

The Journal of cell biology

Gilden JK, Peck S, Chen YC, Krummel MF

Regulation of T cell priming by lymphoid stroma.

PloS one

Khan O, Headley M, Gerard A, Wei W, Liu L, Krummel MF

Stabilized imaging of immune surveillance in the mouse lung.

Nature methods

Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics.

The Journal of experimental medicine

Friedman RS, Beemiller P, Sorensen CM, Jacobelli J, Krummel MF

Duration of antigen receptor signaling determines T-cell tolerance or activation.

Proceedings of the National Academy of Sciences of the United States of America

Katzman SD, O'Gorman WE, Villarino AV, Gallo E, Friedman RS, Krummel MF, Nolan GP, Abbas AK

Confinement-optimized three-dimensional T cell amoeboid motility is modulated via myosin IIA-regulated adhesions.

Nature immunology

Jacobelli J, Friedman RS, Conti MA, Lennon-Dumenil AM, Piel M, Sorensen CM, Adelstein RS, Krummel MF

Mediation of T-cell activation by actin meshworks.

Cold Spring Harbor perspectives in biology

Beemiller P, Krummel MF

The immunological synapse: a dynamic platform for local signaling.

Journal of clinical immunology

Krummel MF, Cahalan MD

Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.

Nature immunology

Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA

Matthew Krummel: visions enumerated. Interview by Amy Maxmen.

The Journal of experimental medicine

Krummel M

Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues.

Journal of immunology (Baltimore, Md. : 1950)

Melli K, Friedman RS, Martin AE, Finger EB, Miao G, Szot GL, Krummel MF, Tang Q

Myosin-IIA and ICAM-1 regulate the interchange between two distinct modes of T cell migration.

Journal of immunology (Baltimore, Md. : 1950)

Jacobelli J, Bennett FC, Pandurangi P, Tooley AJ, Krummel MF

Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility.

Nature cell biology

Tooley AJ, Gilden J, Jacobelli J, Beemiller P, Trimble WS, Kinoshita M, Krummel MF

Normal development and activation but altered cytokine production of Fyn-deficient CD4+ T cells.

Journal of immunology (Baltimore, Md. : 1950)

Mamchak AA, Sullivan BM, Hou B, Lee LM, Gilden JK, Krummel MF, Locksley RM, DeFranco AL

Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy.

Disease models & mechanisms

Egeblad M, Ewald AJ, Askautrud HA, Truitt ML, Welm BE, Bainbridge E, Peeters G, Krummel MF, Werb Z

Deletional tolerance mediated by extrathymic Aire-expressing cells.

Science (New York, N.Y.)

Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X, Johannes KP, Su MA, Chang HY, Krummel MF, Anderson MS

A synaptic basis for paracrine interleukin-2 signaling during homotypic T cell interaction.

Immunity

Sabatos CA, Doh J, Chakravarti S, Friedman RS, Pandurangi PG, Tooley AJ, Krummel MF

Testing the organization of the immunological synapse.

Current opinion in immunology

Krummel MF

Maintenance and modulation of T cell polarity.

Nature immunology

Krummel MF, Macara I

Surface-bound chemokines capture and prime T cells for synapse formation.

Nature immunology

Friedman RS, Jacobelli J, Krummel MF

Imaging the function of regulatory T cells in vivo.

Current opinion in immunology

Tang Q, Krummel MF

Triggering of T cell activation via CD4 dimers.

Journal of immunology (Baltimore, Md. : 1950)

Moldovan MC, Sabbagh L, Breton G, Sékaly RP, Krummel MF

Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice.

Nature immunology

Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA

Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells.

PLoS biology

Okada T, Miller MJ, Parker I, Krummel MF, Neighbors M, Hartley SB, O'Garra A, Cahalan MD, Cyster JG

T cell synapse assembly: proteins, motors and the underlying cell biology.

Seminars in immunology

Tooley AJ, Jacobelli J, Moldovan MC, Douglas A, Krummel MF

Immunological synapse formation licenses CD40-CD40L accumulations at T-APC contact sites.

Journal of immunology (Baltimore, Md. : 1950)

Boisvert J, Edmondson S, Krummel MF

New views of the immunological synapse: variations in assembly and function.

Current opinion in immunology

Jacobelli J, Andres PG, Boisvert J, Krummel MF

CD28 signals in the immature immunological synapse.

Journal of immunology (Baltimore, Md. : 1950)

Andres PG, Howland KC, Dresnek D, Edmondson S, Abbas AK, Krummel MF

A single class II myosin modulates T cell motility and stopping, but not synapse formation.

Nature immunology

Jacobelli J, Chmura SA, Buxton DB, Davis MM, Krummel MF

Quantifying signaling-induced reorientation of T cell receptors during immunological synapse formation.

Proceedings of the National Academy of Sciences of the United States of America

Moss WC, Irvine DJ, Davis MM, Krummel MF