Principal Investigator
Member
Ragon Institute of Mass General, MIT, and Harvard
Associate Professor
IMES, Chemistry, and Koch Institute, MIT
Institute Member
Broad Institute of MIT and Harvard
617.324.5670
E25-348a
The Shalek Lab develops and applies broadly-applicable experimental and computational platforms to comprehensively examine and rationally engineer human immune responses in tissues. Our underlying goals are to empower basic biological discovery and transform preventions and cures for autoimmune, infectious, and cancerous diseases. Through creating and implementing comprehensive single-cell and tissue profiling and manipulation tools across organs, models, and diseases with partners around the world, we are systematically examining how cellular composition and communication underpin tissue function and dysfunction; by coupling our discoveries with methodical validations, we are actively identifying preventions and cures to maintain or reestablish human health.
The interdisciplinary research in the Shalek Lab 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, the lab couples genomics, chemical biology, and nanotechnology to establish accessible, broadly-applicable cross-disciplinary platforms that enable them and others to profile and control cells and their interactions. 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.
Alex Shalek and his lab have received numerous honors including a NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, the Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), and an Alfred P. Sloan Research Fellowship in Chemistry, as well as the 2019-2020 Harold E. Edgerton Faculty Achievement Award at MIT and a Young Mentor Award from Harvard Medical School.
Alex K. Shalek, PhD, is a Core Member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of The Koch Institute for Integrative Cancer Research at MIT. He is also an Institute Member of the Broad Institute, a Member of the Ragon Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. Alex received his bachelor's degree summa cum laude from Columbia University and his Ph.D. from Harvard University in chemical physics.
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 Methods, 14, 395 (2017)
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)
Tu, A.A.#, Gierahn, T.M.#, Monian, B., Morgan, D.M., Mehta, N.K., Ruiter, B., Shreffler, W.G., Shalek, A.K.*, and Love, J.C.*
Nature Immunology, 20, 1692 (2019)
Kotliar, D.#, Lin, A.E.#, Logue, J., Hughes, T.K., Khoury, N., Raju, S.S., Wadsworth II, M.H., Chen, H., Kurtz, J.R., Dighero-Kemp, B., Bjornson, Z.B., Mukherjee, N., Sellers, B., Tran, N., Bauer, M.R., Adams, G.C., Adams, R., Rinn, J.L., Melé, M., Nolan, G.P., Barnes, K.G., Hensley, L.E.*, McIlwain, D.R.*, Shalek, A.K.*, Sabeti, P.C.*, and Bennett, R.S.*
Cell, 183, 1383 (2020).
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)
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)
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)
Delorey, T.M.#, Ziegler, C.G.K.#, Heimberg, G.#, Normand, R.#, Yang, Y.#, Segerstolpe, A.#, Abbondanza, D.#, Fleming, S.J.#, Subramanian, A.#, Jagadeesh, K.A.#, Dey, K.#, Slyper, M.#, Montoro, D.T.#, Pita-Juarez, Y. #, Phillips, D.#, Sen, P.#, Bloom-Ackerman, Z., Ganna, A., Gomez, J., Normandin, E., Naderi, P., Popov, Y., Niezen, S., Tsai, L., Siddle, K.J., Sud, M., Tran, V.M., Vellarikkal, S.K., Amir-Zilberstein, L., Atri, D.S., Barkas, N., Brook, O.R., Chen, J., Divakar, P., Dorceus, P., Engreitz, J.M., Fitzgerald, D.M., Fropf, E., Gazel, S., Gould, J., Grzyb, J., Harvey, T., Hecht, J., Jane-Valbuena, J., Leney-Greene, M., Ma, H., McCabe, C., McLoughlin, D.E., Miller, E.M., Muus, C., Niemi, M., Padera, R., Pfiffner-Borges, J., Pinto, C.J., Plaisted, J., Raju, S.S., Ross, M., Rucy, M., Rueckert, E.H., Siciliano, M., Strum, A., Todres, E., Waghray, A., Warren, S., Zhang, S., Zollinger, D., Cosimi, L., Gupta, R.M., Hacohen, N., Price, A.L., Rajagopal, J., Tata, P.R., Tickle, T.L., Hung, D.*, Sabeti, P.C.*, Novak, R.*, Rogers, R.*, Ingber, D.E.*, Jiang, Z.G.*, Juric, D.*, Babadi, M.*, Farhi, S.L.*, Stone, J.*, Vlachos, I.S.*, Solomon, I.H.*, Ashenberg, O.*, Porter, C.B.M.*, Li, B.*, Shalek, A.K.*, Villani, A.-C.*, Rozenblatt-Rosen, O.*, and Regev, A.*
Nature,595, (2021)
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