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

Publications

Minimalistic Transcriptomic Signatures Permit Accurate Early Prediction of COVID-19 Mortality.

medRxiv : the preprint server for health sciences

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

Immediate myeloid depot for SARS-CoV-2 in the human lung.

Science advances

Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Bernard O, Simoneau CR, Hysenaj L, Hu KH, Maishan M, Conrad C, Gbenedio OM, Samad B, Consortium TUC, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.

iScience

Hackney JA, Shivram H, Vander Heiden J, Overall C, Orozco L, Gao X, Kim E, West N, Qamra A, Chang D, Chakrabarti A, Choy DF, Combes AJ, Courau T, Fragiadakis GK, Rao AA, Ray A, Tsui J, Hu K, Kuhn NF, Krummel MF, Erle DJ, Kangelaris K, Sarma A, Lyon Z, Calfee CS, Woodruff PG, Ghale R, Mick E, Byrne A, Zha BS, Langelier C, Hendrickson CM, van der Wijst MGP, Hartoularos GC, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Ye CJ, UCSF COMET Consortium, Ramalingam T, McBride JM, Cai F, Teterina A, Bao M, Tsai L, Rosas IO, Regev A, Kapadia SB, Bauer RN, Rosenberger CM

TREM1 activation of myeloid cells promotes antitumor immunity.

Science translational medicine

Juric V, Mayes E, Binnewies M, Lee T, Canaday P, Pollack JL, Rudolph J, Du X, Liu VM, Dash S, Palmer R, Jahchan NS, Ramoth ÅJ, Lacayo S, Mankikar S, Norng M, Brassell C, Pal A, Chan C, Lu E, Sriram V, Streuli M, Krummel MF, Baker KP, Liang L

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Stem cell reports

Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP

Immediate myeloid depot for SARS-CoV-2 in the human lung.

bioRxiv : the preprint server for biology

Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Simoneau CR, Hysenaj L, Hu KH, UCSF COMET Consortium, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR

Discovering dominant tumor immune archetypes in a pan-cancer census.

Cell

Combes AJ, Samad B, Tsui J, Chew NW, Yan P, Reeder GC, Kushnoor D, Shen A, Davidson B, Barczak AJ, Adkisson M, Edwards A, Naser M, Barry KC, Courau T, Hammoudi T, Argüello RJ, Rao AA, Olshen AB, Immunoprofiler Consortium, Cai C, Zhan J, Davis KC, Kelley RK, Chapman JS, Atreya CE, Patel A, Daud AI, Ha P, Diaz AA, Kratz JR, Collisson EA, Fragiadakis GK, Erle DJ, Boissonnas A, Asthana S, Chan V, Krummel MF

Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

medRxiv : the preprint server for health sciences

Tsitsiklis A, Zha BS, Byrne A, Devoe C, Levan S, Rackaityte E, Sunshine S, Mick E, Ghale R, Jauregui A, Sarma A, Neff N, Serpa PH, Deiss TJ, Kistler A, Carrillo S, Ansel KM, Leligdowicz A, Christenson S, Jones N, Wu B, Darmanis S, Matthay MA, Lynch SV, DeRisi JL, COMET Consortium+ , Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Rosenberg O, Calfee CS, Langelier CR

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

EClinicalMedicine

Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez-Fuertes M, Wang X, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Wolfgang P, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B

Layilin Anchors Regulatory T Cells in Skin.

Journal of immunology (Baltimore, Md. : 1950)

Mehta P, Gouirand V, Boda DP, Zhang J, Gearty SV, Zirak B, Lowe MM, Clancy S, Boothby I, Mahuron KM, Fries A, Krummel MF, Mankoo P, Chang HW, Liu J, Moreau JM, Scharschmidt TC, Daud A, Kim E, Neuhaus IM, Harris HW, Liao W, Rosenblum MD

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

Nature communications

Sarma A, Christenson SA, Byrne A, Mick E, Pisco AO, DeVoe C, Deiss T, Ghale R, Zha BS, Tsitsiklis A, Jauregui A, Moazed F, Detweiler AM, Spottiswoode N, Sinha P, Neff N, Tan M, Serpa PH, Willmore A, Ansel KM, Wilson JG, Leligdowicz A, Siegel ER, Sirota M, DeRisi JL, Matthay MA, COMET Consortium , Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Calfee CS, Langelier CR

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Science translational medicine

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, Le Voyer T, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ, UCSF COMET consortium

Publisher Correction: Global absence and targeting of protective immune states in severe COVID-19.

Nature

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

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator.

bioRxiv : the preprint server for biology

Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19.

bioRxiv : the preprint server for biology

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

Global absence and targeting of protective immune states in severe COVID-19.

Nature

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

Visualizing Cancer.

Cancer cell

Krummel M, Hu K, de Vries EGE, Goetz JG, Passaro D, Subramaniam S, Misteli T, Skala M, Bravo-Cordero JJ, Sutcliffe JL

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

bioRxiv : the preprint server for biology

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.

Research square

Krummel M, Combes A, Courau T, Kuhn N, Hu K, Ray A, Chen W, Cleary S, Chew N, Kushnoor D, Reeder G, Shen A, Tsui J, Hiam K, Sandoval PM, Zhu W, Lee D, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik C, Loudermilk R, Wilson M, Ye C, Fragiadakis G, Looney M, Chan V, Ward A, Carrillo S, Matthay M, Erle D, Woodruff P, Langelier C, Kangelaris K, Hendrickson C, Calfee C, Rao A

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

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

Visualizing T-cell recognition.

Cold Spring Harbor symposia on quantitative biology

Davis MM, Wülfing C, Krummel MF, Savage PA, Xu J, Sumen C, Dustin ML, Chien YH