The interdisciplinary research in the Shalek Lab aims to create and implement new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. This encompasses both the development of broadly enabling technologies as well as their application to characterize, model, and rationally control complex multicellular systems. With respect to technology development, we couple genomics, chemical biology, and nanotechnology to establish accessible, broadly-applicable cross-disciplinary platforms that enable us and others to profile and control cells and their interactions within complex multicellular systems. In addition to sharing this toolbox to empower mechanistic scientific inquiry across the global research community, we are applying it to uncover principles that inform ensemble immune responses within tissues, focusing on the roles of cellular heterogeneity and cell-to-cell communication. Current studies with partners around the world seek to methodically dissect human disease to understand links between cellular features and clinical observations, including how: immune cells coordinate balanced responses to environmental changes with tissue-resident cells; host cell-pathogen interactions evolve across time and tissues during pathogenic infection; and, tumor cells evade homeostatic immune activity. From these observations and those of others, we aim to construct a unified understanding of how disease alters tissue function at the cellular level and realize therapeutic and prophylactic interventions to reestablish or maintain human health. Overall, we hope that our principled, comprehensive approach not only provides valuable experimental and computational tools to advance many avenues of scientific inquiry, but also transforms how the community studies and engineers human immune responses in tissues.
The Shalek Lab creates and implements new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease.
Office
E25-348APhone
617-324-5670Administrative Assistant
Jeff GahanAssistant Phone
617-715-2247Alex K. Shalek
J. W. Kieckhefer Professor in the Institute for Medical Engineering and Science and the Department of Chemistry
Director of Health Innovation Hub
Director, Institute for Medical Engineering and Science, MIT
Extramural Member, The Koch Institute for Integrative Cancer Research, MIT
Member, Ragon Institute of MGH, MIT, and Harvard
Institute Member, Broad Institute of MIT and Harvard
Assistant in Immunology, Massachusetts General Hospital
Instructor, Health Sciences and Technology, Harvard Medical School
Research Areas
Office
E25-348APhone
617-324-5670Administrative Assistant
Jeff GahanAssistant Phone
617-715-2247Key Publications
See all on the Shalek Group WebsiteMultimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control
Gideon, H#, Hughes, T.K.#, Wadsworth, M.H., Tu, A.A., Gierahn, T.M., Hopkins, F.F., Wei, J.-R., Kummerlowe, C., Grant, N.L., Nargan, K., Phuah, J., Borish, H.J., Maiello, P., White, A.G., Ganchua, S.K.C., Myers, A., Ameel, C.L., Cochran, C.T., Nyquist, S.K., Peters, J.M., Tomko, J.A., Frye, L.J., Rosenberg, J.M., Shih, A., Chao, M., Scanga, C.A., Ordovas-Montanes, J., Berger, B., Mattila, J.T., Madansein, R., Love, J.C., Bryson, B., Lin, P.L., Leslie, A., Behar, S.M., Flynn, J.L*, Fortune, S.M.*, and Shalek, A.K.*, Immunity, 55, 1 (2022).
Full text at PubMedTranscriptional subtype-specific microenvironmental crosstalk and tumor cell plasticity in metastatic pancreatic cancer
Raghavan, S.#, Winter,,S.#, Navia, A.W.#, Williams, H.L., DenAdel, A., Kalekar, R.L., Galvez-Reyes, J., Lowder, K.E., Mulugeta, N., Raghavan, M.S., Borah, A.A., Väyrynen, S.A., Costa, A.D., Ng, R.W.S., Wang, J., Reilly, E., Ragon, D., Brais, L.K., Jaeger, A.M., Spurr, L.F., Li, Y.Y., Cherniak, A.D., Wakrio, I., Rotem, A., Johnson, B.E., McFarland, J.M., Sicinska, E., Jacks, T., Clancy, T.E., Perez, K., Rubinson, D.A., Ng, K., Cleary, J.M., Crawford, L., Manalis, S.R., Nowak, J.A., Wolpin, B.M.*, Hahn, W.C.*, Aguirre, A.J.*, and Shalek, A.K.*, Cell, 184 6119 (2021).
Full text at bioRxivImpaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
Ziegler, C.G.K.#, Miao, V.N.#, Owings, A.H.#, Navia, A.W.#, Tang, Y.#, Bromley, J.D.#, Lofty, P., Sloan, M., Laird, H., Williams, H.B., George, M., Drake, R.S., Christian, T., Parker, A., Sindel, C.B., Burger, M.W., Pride, Y., Hasan, M., Abraham, G.E., Senitko, M., Robinson, T.O.,Shalek, A.K.*, Glover, S.C.*, Horwitz, B.H.*, and Ordovas-Montanes, J.*, Cell, 184 4713 (2021).
Full text at ScienceDirectLymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential
Huang, S.#, Ziegler, C.G.K.#, Austin, J., Mannoun, N., Ordovas-Montanes, J., Vukovic, M., Shalek, A.K.* and Von Andrian, U.*, Cell, AOP, (2020); bioRxiv 833509
Full text at PubMedSecond Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies
Hughes, T.K.#, Wadsworth II, M.H.#, Gierahn, T.M.#, Do, T., Weiss, D., Andrade, P., Ma, F., Andrade, B., Shao, B., Tsoi, L.C., Gudjonsson, J.E., Modlin, R.L., Love, J.C.*, and Shalek, A.K.*, Immunity, 53, 878 (2020).
Full text at PubMedSARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues
Ziegler, C.G.K.#, Allon, S.J.#, Nyquist, S.K.#, Mbano, I.M.#, Miao, V.N., Tzouanas, C.N., Cao, Y., Yousif, A.S., Bals, J., Hauser, B.M., Feldman, J., Muus, C., Wadsworth II, M.H., Kazer, S.W., Hughes, T.K., Doran, B., Gatter, G.J., Vukociv, M., Taliaferro, F., Mead, B.E., Guo, Z., Wang, J.P., Gras, D., Plaisant, M., Ansari, M., Angelidis, I., Adler, H., Sucre, J.M.S., Taylor, C.J., Lin, B., Waghray, A., Mitsialis, B., Dwyer, D.F., Bucheit, K.M., Boyce, J.A., Barrett, N.A., Laidlaw, T.M., Carroll, S.L., Colonna, L., Tkachev, V., Peterson, C.W., Yu, A., Zheng, H.B., Gideon, H.P., Winchell, C.G., Lin, P.L., Bingle, C.D., Snapper, S.B., Kropski, J.A., Theis, F.J., Schiller, H.B., Zaragosi, L.-E., Barbry, P., Berger, B.A., Leslie, A., Kiem, H.-P., Flynn, J.L., Fortune, S.M., Finberg, R.W., Kean, L.S., Garber, M., Schmidt, A., Lingwood, D., Shalek, A.K.*, Ordovas-Montanes, J.*, and the HCA Lung Biological Network, Cell, 181, 1016 (2020).
Full text at PubMedIntegrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection
Kazer S.W., Aicher, T.P., Muema, D., Carroll, S.L., Ordovas-Montanes J., Ziegler, C.G.K., Nyquist, S.K., Wong, E.B., Ismail, N., Dong, M., Moodley, A., Dong, K., Ndhlovu, Z.M, Ndung’u T., Walker, B.D.*, and Shalek, A.K*, Nature Medicine, 26, 511 (2020).
Full text at bioRxivRewiring of the cellular and inter-cellular landscape of the human colon during ulcerative colitis
Smillie, C.#, Biton, M.#, Ordovas-Montanes, J.#, Sullivan, K., Burgin, G., Graham, D.B., Herbst, R.H., Rogel, N., Slyper, M., Walkman, J., Sud, M., Andrews, E., Haber, A.L., Vickovic, S., Dionne, D., Nguyen, L.T., Villani, A.C., Hofree, M., Creasey, E.A., Huang, H., Rozenblatt-Rosen, O., Garber, J.J., Khalili, H., Desch, A.N., Daly, M.J., Ananthakrishnan, A.N.*, Shalek, AK.*, Xavier, RJ.*, and Regev, A.*, Cell, 178, 714 (2019).
Full text at bioRxivReduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity
Ordovas-Montanes, J.#, Dwyer, D.F.#, Nyquist, S.K., Buchheit, K.M., Deb, C., Wadsworth, M.H., Hughes, T.K., Kazer, S.W., Yoshimoto, E., Bhattacharyya, N., Katz, H.R., Berger, B., Laidlaw, T.M., Boyce, J.A., Barrett, N.A.*, and Shalek, A.K.*, Nature, 560, 649 (2018).
Full text at bioRxivSeq-Well: A Portable, Low-cost Platform for Single-Cell RNA-Seq of Low-Input Samples
Gierahn, T.#, Wadsworth II, M.H. #, Hughes, T.K. #, Bryson, B.D., Butler, A., Satija, R., Fortune, S., Love, J.C.*, and Shalek, A.K.*, Nature Meth., 14, 395 (2017).
Full text at PubMed