Mikala Egeblad, Ph.D.

Bloomberg Distinguished Professor

410-955-9938

Johns Hopkins University School of Medicine
855 N. Wolfe Street, 451 Rangos Bldg

 

Lab website

Academic Titles

Bloomberg Distinguished Professor of Tumor Microenvironment

Appointments/Affiliations

Professor of Cell Biology
Professor of Oncology
Co-Leader, Cancer Invasion and Metastasis Program, Sidney Kimmel Comprehensive Cancer Center

Research Topic

The Egeblad lab studies the contributions of the tumor microenvironment – in which cancer cells arise and live – to therapy responses and metastasis. Solid tumors are abnormally organized tissues that contain not only cancer cells, but also various stromal cell types and extracellular matrix, and these latter components constitute the microenvironment. Communications between the different components of the tumor influence its growth, its response to therapy, and its ability to metastasize. The lab studies the importance of tumor-stroma communications using co-culture assays and mouse models of breast and pancreatic cancer. We use co-culture assays to interrogate signaling pathways involved in communications between cancer cells and specific types of stromal cells (e.g., macrophages, neutrophils and fibroblasts). We use microscopy of tumors in live mice to determine how interactions between cancer and stromal cells or activation of specific signaling pathways influence cellular survival, proliferation and migration. We use bioluminescence and small animal ultrasound to follow tumor progression and regression at the organism level. Our main focus is on the functions of myeloid-derived immune cells, a diverse group of cells that can enhance angiogenesis and metastasis and suppress the response to chemotherapy and the cytotoxic immune responses against tumors. We study how different types of myeloid cells are recruited to tumors and how signals between them and the cancer cells, or other immune cells, influence response to chemotherapy and metastatic spread.

 

Further Information

Triggering the body’s defenses to fight cancer.Nautilus, November13 (2021)

The Scientist, May 28 (2020)
Scientific American, April 28 (2020)
The Scientist, October 1 (2019)
Oncology Times, January 5 (2018)

Associated Faculty

Name Title Email Phone
Jose M. Adrover Research Associate (Egeblad Lab) adrover@jhu.edu

Lab Members

Name Classification Email Phone
Amir Ameri, Ph.D Postdoctoral Fellow aameri2@jhmi.edu
Emily Cao Student ecao2@jh.edu
Jose M. Adrover Student adrover@jhu.edu
Lijuan Sun Student lsun51@jh.edu
Sicheng Pan Student span28@jhu.edu
Xiao Han Student xhan53@jh.edu

Publications

  • Maiorino, L., Shevik, M., Adrover, J.M., Han, X., Georgas, E., Wilkinson, J.E., Seidner, H., Foerschner, L., Tuveson, D.A., Qin, Y.-X., and Egeblad M. (2022) Longitudinal intravital imaging through clear silicone windows. J Vis Exp, 179, e62757, doi:10.3791/6275.
  • Maiorino, L., Daßler-Plenker, J., Sun, L, and Egeblad, M. (2022) Innate Immunity and Cancer Pathophysiology. Annu Rev Pathol. 2021. doi: 10.1146/annurev-pathmechdis-032221-115501.
  • Adrover, J.M., Carrau, L., Daßler-Plenker, J., Bram, Y., Chandar, V., Houghton, S., Redmond, D., Merrill, J.R., Shevik, M., tenOever, B.R., Lyons, S.K., Schwartz, R.E., and Egeblad M. (2022) Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection. JCI Insight, 7: e157342. https://doi.org/10.1172/jci.insight.157342.
  • Quail, D.F., Amulic, B., Aziz, M., Barnes, B.J., Eruslanov, E., Fridlender, Z.G., Goodridge, H.S., Granot, Z., Hidalgo, A., Huttenlocher, A., Kaplan, M.J., Malanchi, I., Merghoub, T., Meylan, E., Mittal, V., Pittet, M.J., Rubio-Ponce, A., Udalova, I.A., van den Berg, T.K., Wagner, D.D., Wang., P., Zychlinsky, A., de Visser, K.E., Egeblad M., Kubes, P. (2022) Neutrophil phenotypes and functions in cancer: a consensus statement J Exp Med , 219(6):e20220011. doi: 10.1084/jem.20220011.
  • Wu, XS, He, X.-Y., Ipsaro, J.J., Huang, Y.-H., Preall, J.B., Ng, D., Shue, Y.T., Egeblad M., Joshua-Tor, L., and Vakoc, C.R. (2022) OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage. Nature doi: 10.1038/s41586-022-04842-7.
  • Song, D., Adrover, J.M, Felice, C., Christensen, L., He, X.-Y., Merrill, J.R., Wilkinson, J.E., Janowitz, T. Lyons, S.K., Egeblad M., and Tonks, N.K. (2022) PTP1B inhibitors regulate the CXCR4-CXCR2 signaling axis in neutrophils and protect against acute lung injury. JCI Insight 7(14):e158199. doi: 10.1172/jci.insight.158199.
  • Olsen T., Caruana D., Cheslack-Postava K., Szema A., Thieme J., Kiss A., Singh M., Smith G., McClain S., Glotch T., Esposito M., Promisloff R., Ng D., He X., Egeblad M., Kew R., Szema A. (2022) Iraq/Afghanistan war lung injury reflects burn pits exposure. Sci Rep. 12(1):14671. doi: 10.1038/s41598-022-18252-2.
  • Fujii T., Rehman H., Chung S.Y., Shen J., Newman J., Wu V., Hines A., Azimi-Nekoo E., Fayyaz F., Lee M., Raptis G., Egeblad M., and Zhu X. (2021) Treatment with Granulocyte-colony Stimulating Factor (G-CSF) is not associated with Increased Risk of Brain Metastasis in Patients with De Novo Stage IV Breast Cancer. J Cancer. 12:5687-5692. doi: 10.7150/jca.63159. eCollection 2021.
     
  • Sun L., Kees T., Almeida A.S., Liu B., He X.Y., Ng D., Han X., Spector D.L., McNeish I.A., Gimotty P., Adams S., and Egeblad M. (2021) Activating a collaborative innate-adaptive immune response to control breast and ovarian cancer metastasis. Cancer Cell, 39, 1361-1374.
  • Barth N.D., Mendive-Tapia L., Subiros-Funosas R., Ghashghaei O., Lavilla R., Maiorino L., He X.Y., Dransfield I., Egeblad M., and Vendrell M. (2021) A Bivalent Activatable Fluorescent Probe for Screening and Intravital Imaging of Chemotherapy-Induced Cancer Cell Death. Angew Chem Int Ed Engl. doi: 10.1002/anie.202113020.
  • Middleton, E.A., He,X.-Y., Denorme, F., Campbell, R.A., Ng, D., Salvatore, S.P., Mostyka, M., Baxter-Stoltzfus, A., Borczuk, A.C., Loda, M., Cody, M.J., Manne, B.K., Portier, I., Harris, E.S., Petrey, A.C., Beswick,E.J., Caulin, A.F., Lovino, A., Abegglen, L.M., Weyrich, A.S., Rondina, M.T., Egeblad M., Schiffman, J.D., and Yost, C.C.(2020). Neutrophil extracellular traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood, 136:1169-1179. doi.org/10.1182/blood.2020007008.
  • Sindhwani, S., Syed, A.M., Ngai, J., Kingston, B.R., Maiorino, L., Rothschild, J., MacMillan, P., Zhang, Y., Rajesh, N.U., Hoang, T., Wu, J.L.Y., Wilhelm, S., Zilman, A., Gadde, S., Sulaiman, A., Ouyang, B., Lin, Z., Wang, L., Egeblad M., and Chan, W.C.W. (2020). The entry of nanoparticles into solid tumours. Nat Mater, 19, 566-575. doi: 10.1038/s41563-019-0566-2.
  • Zuo, Y., Yalavarthi, S., Shi, H., Gockman, K., Zuo, M., Madison, J.A., Blair, C.N., Weber, A., Barnes, B.J., Egeblad M., Woods, R.J., Kanthi, Y., and Knight, J.S. (2020). Neutrophil extracellular traps in COVID-19. JCI Insight, 5:138999. doi: 10.1172/jci.insight.138999.
  • Somerville, T.D., Biffi, G., Daßler-Plenker, J., Hur, S.K., He, X.Y., Vance, K.E., Miyabayashi, K., Xu, Y., Maia-Silva, D., Klingbeil, O., Demerdash, O.E., Preall, J.B., Hollingsworth, M.A.,Egeblad M., Tuveson, D.A., and Vakoc, C.R. (2020). Squamous trans-differentiation of pancreatic cancer cells promotes stromal inflammation. Elife 9:e53381. doi: 10.7554/eLife.53381.
     
  • Weber, A.G., Chau, A.S.,Egeblad M., Barnes, B.J., and Janowitz, T. (2020). Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series. Mol Med. 26:91. doi: 10.1186/s10020-020-00215-w.
  • Barth, N., Subiros-Funosas, R., Mendive-Tapia, L., Duffin, R., Shields, M., Cartwright, J., Henriques, S., Sot, J., Goñi, F., Lavilla, R., Marwick, J., Vermeren, S., Rossi, A., Egeblad M., Dransfield, I., and Vendrell, M. (2020). A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis. Nat Comm, 11:4027. doi: 10.1038/s41467-020-17772-7.
  • Rozenblit, M., Hendrickx, W., Heguy, A., Chiriboga, L., Loomis C., Ray, K., Darvishian, F., Egeblad M., Demaria, S., Marincola, F., Bedognetti, D., and Adams, S. (2019). Transcriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod. Sci Rep, 9(1), 8572. doi: 10.1038/s41598-019-42784-9.
  • Bružas, E., Egeblad M. (2018) Spotlight: Bone talk: activated osteoblasts promote lung cancer growth. Trends Mol Med, Published online: February 02, 2018
  • Pommier A, Anaparthy N, Memos N, Kelley ZL, Gouronnec A, Yan R, Auffray C, Albrengues J, Egeblad M., Iacobuzio-Donahue CA, Lyons SK, Fearon DT. (2018) Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases. Science 360. pii: eaao4908. doi: 10.1126/science.aao4908
  • Huang YH, Klingbeil O, He XY, Wu XS, Arun G, Lu B, Somerville TDD, Milazzo JP, Wilkinson JE, Demerdash OE, Spector DL, Egeblad M., Shi J, Vakoc CR. (2018) POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes Dev 32:915-928. doi: 10.1101/gad.314815.118
  • Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, Upadhyay P, Uyeminami DL, Pommier A, Küttner V, Bružas E, Maiorino L, Bautista C, Carmona EM, Gimotty PA, Fearon DT, Chang K, Lyons SK, Pinkerton KE, Trotman LC, Goldberg MS, Yeh JT, Egeblad M. (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361. pii: eaao4227. doi: 10.1126/science.aao4227
     
  • Fein, M.R., He, X.-Y., Almeida, A.S., Bružas, E., Pommier, A., Yan, R., Eberhardt, A., Fearon, D.T., Van Aelst L., Wilkinson, J.E., dos Santos, C.O., and Egeblad M. (2018). Cancer cell CCR2 orchestrates suppression of the adaptive immune response. JEM, 217: e20181551. doi: 10.1084/jem.20181551.
  • Perurena N., Zandueta C., Martínez-Canarias S., Moreno H., Vicent S., Almeida A.S., Guruceaga E., Gomis R.R., Santisteban M., Egeblad M., Hermida J., and Lecanda F. (2017) EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth. J Hematol Oncol;10(1):23. doi: 10.1186/s13045-017-0399-x.
  • Öhlund D., Handly-Santana A., Biffi G., Elyada E., Almeida A.S., Ponz-Sarvise M., Corbo V., Oni T.E., Hearn S.A., Lee E.J., Chio I.I., Hwang C.I., Tiriac H., Baker L.A., Engle D.D., Feig C., Kultti A., Egeblad M., Fearon D.T., Crawford J.M., Clevers H., Park Y., and Tuveson D.A. (2017) Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med, 214:579-596.
  • Roe J.S., Hwang C.I., Somerville T.D.D., Milazzo J.P., Lee E.J., Da Silva B., Maiorino L., Tiriac H., Young C.M., Miyabayashi K., Filippini D., Creighton B., Burkhart R.A., Buscaglia J.M., Kim E.J., Grem J.L., Lazenby A.J., Grunkemeyer J.A., Hollingsworth M.A., Grandgenett P.M., Egeblad M., Park Y., Tuveson D.A., and Vakoc C.R. (2017) Enhancer reprogramming promotes pancreatic cancer metastasis. Cell, 170, 875-888.
  • Albrengues, J., Wysocki, R.W., Maiorino, L., Egeblad M. (2017) Preview: Re-cyclin’ cell-cycle components to make NETs. Dev Cell, 43, 379-80.
  • Arun, G., Diermeier, S., Akerman, M., Chang, K.-C., Wilkinson, J. E., Hearn, S., Kim, Y., MacLeod, A.R., Krainer, A., Norton, L., Brogi, E., Egeblad, M. and Spector, D. L. (2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 LncRNA loss. Genes Dev, 30, 34-51.
  • Park, J., Wysocki, R.W., Amoozgar, Z., Maiorino, L., Fein, M.R., Jorns, J., , Schott, A.F., Kinugasa-Katayama, Y., Lee, Y., Won, N.H., Nakasone, E.S., Hearn, S.A., Küttner,V., Qiu, J., Almeida, A.S., Perurena, N., Kessenbrock, K., Goldberg M.S., and Egeblad. M. (2016) Cancer cells trigger neutrophils to induce metastasis-supporting extracellular DNA traps. Sci Transl Med 8, 361ra138
  • Park, J.-H., Rasch, M.R., Qiu J., Lund I.K., Egeblad, M. (2015) Presence of insulin-like growth factor binding proteins correlates with tumor-promoting effects of matrix metalloproteinase 9 in breast cancer. Neoplasia, 17, 421-33.
  • Ewald, A.J. and Egeblad M. (2014) Cancer: Sugar-coating cell signalling. Nature, 51:298-9.
  • Nakasone, E. S, Askautrud, H. A., and Egeblad, M. (2013) Live imaging of drug responses in the tumor microenvironment in mouse models of breast cancer. J Vis Exp, 73, doi: 10.3791/50088.
  • Rajaram M., Li J., Egeblad M., Powers R.S. (2013) System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenecity. PLoS Genet, 9(9):e1003789.
  • Fein, M. R., and Egeblad, M. (2013) Caught in the Act: Revealing the Metastatic Process by Live Imaging. Dis Model Mech, 6(3):580-93. doi: 10.1242/dmm.009282.
  • Engelhardt, J.J., Boldajipour, B., Beemiller, P., Pandurangi, P., Sorenson, C., Werb, Z., Egeblad, M., and Krummel, M.F. (2012). Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell, 21, 402-417.
  • Nakasone, E.S., Askautrud, H.A., Kees , T., Parks, J.-H., Plaks, V., Ewald, A.J., Fein, M., Rasch, M.G., Tan, Y.X., Qiu, J., Park, J., Sinha, P., Bissell, M., Frengen, E., Werb, Z., and Egeblad, M. (2012) Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell, 21, 488-503. Selected for the cover. See also Research Highlights, Nature 2012, 485, 282.
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    Kees, T. and Egeblad, M. (2011). Innate immune cells in breast cancer – from villains to heroes? J Mammary Gland Biol Neoplasia, 16, 189-203.
  • Egeblad, M., Nakasone, E.S., and Werb, Z. (2010). The tumor as an organ: complex tissues that interface with the entire organism. Dev Cell, 18, 884-901.
  • Egeblad M., Rasch, M.G., and Weaver V.M. (2010). Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol, 22, 697-706.
  • Sounni, N.E., Dehne, K., van Kempen, L.C.L., Egeblad, M., Affara, N.I., Cuevas, I., Wisen J., Junankar, S., Korets, L., Lee, J., Shen, J., Morrison, C.J., Overall, C. M., Krane, S.M., Werb, Z., Boudreau, N., and Coussens, L.M. (2010). Stromal Regulation of Vessel Stability by MMP14 and TGFβ. Dis Model Mech, 3, 317-32.
  • Levental, K.R., Yu, H., Kass, L., Lakins, J.N., Egeblad, M., Erler J.T., Fong, S.F., Csiszar, K.L., Giaccia, A., Weninger, W., Yamauchi, M., Gasser, D.L., and Weaver, V.M. (2009). Matrix cross-linking forces tumor progression by enhancing integrin signaling. Cell, 139, 891-906.