Alex K. Shalek, PhD
Core Faculty
Title
J.W. Kieckhefer Professor, IMES, Chemistry, 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, MGH
Instructor, Health Sciences and Technology, HMS
Photo: Alex K. Shalek
Email
shalek [at] mit.edu
Website
Phone
(617) 324-5670
Lab Phone
(617) 324-5670
Address

77 Massachusetts Ave.
Cambridge, MA 02139

Room
E25-348A
Administrative Assistant(s)
Jeff Gahan
(617) 715-2247
jgahan [at] mit.edu
Lab Manager: Nancy Tran
ntran [at] mit.edu
Alex K. Shalek, PhD
Core Faculty
Title
J.W. Kieckhefer Professor, IMES, Chemistry, 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, MGH
Instructor, Health Sciences and Technology, HMS

Degrees

  • PhD in Chemical Physics, Harvard University, 2011
  • AM in Chemical Physics, Harvard University, 2006
  • BA in Chemical Physics, Columbia University, 2004

Bio

Alex K. Shalek, PhD, (pronouns: he/him/his) is the J.W. Kieckhefer Professor in the Institute for Medical Engineering and Science (IMES), and the Department of Chemistry, as well as 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 Harvard Medical School. Dr. Shalek received his bachelor’s degree summa cum laude from Columbia University and his Ph.D. from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). His lab’s research is directed towards the development and application of new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. Dr. Shalek and his work 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 the 2020 HMS Young Mentor Award.

Research

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.

Selected Awards/Societies

  • Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), 2021
  • Young Mentor Award, Harvard Medical School, 2020
  • Harold E. Edgerton Faculty Achievement Award, MIT, 2020
  • Pew-Stewart Scholar, 2018-2022
  • Alfred P. Sloan Research Fellow in Chemistry, 2018 – 2020
  • Associate Editor, Science Advances, 2017 – current
  • Pfizer-Laubach Career Development Professorship, MIT, 2017-2020
  • Associate Scientific Advisor, Science Translational Medicine, 2016
  • NIH New Innovator, 2015
  • Beckman Young Investigator, 2015
  • Searle Scholar, 2015
  • “Follow That Cell” Competition First Place (Team Member), 2015
  • Hermann L.F. Von Helmholtz Career Development Professor, 2014-Present
  • Broad Institute-Israel Partnership for Cell Circuit Research Collaborative Grant, 2013
  • Excellence Award, Broad Institute, 2013
  • Dudley R. Herschbach Teaching Award, Harvard University, 2006
  • Certificate of Distinction in Teaching, Harvard University, 2005
  • National Science Foundation Graduate Research Fellowship, 2005-2008
  • Phi Beta Kappa, Columbia University, 2004
  • John Jay Scholar, Columbia University, 2000-2004
  • Dean’s List, Columbia University, 2000-2004

Selected Publications

  • 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.*, “Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control,” Immunity, 55, 1 (2022).
  • 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.*, “Transcriptional subtype-specific microenvironmental crosstalk and tumor cell plasticity in metastatic pancreatic cancer,” Cell184 6119 (2021).
  • 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.*, “Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19,” Cell 184 4713 (2021).
  • Huang, S.#, Ziegler, C.G.K.#, Austin, J., Mannoun, N., Ordovas-Montanes, J., Vukovic, M., Shalek, A.K.* and Von Andrian, U.*, “Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential.” Cell, 184, 441 (2021).
  • 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.*, “Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics,” Cell, 183, 1 (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.*, “Second Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies,” Immunity, 53, 878 (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, “SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues,” Cell, 181, 1016 (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*, “Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection,” Nature Medicine, 26, 511 (2020).
  • 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.*, “Rewiring of the cellular and inter-cellular landscape of the human colon during ulcerative colitis,” Cell, 178, 714 (2019).
  • 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.*, “Reduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity,” Nature, 560, 649 (2018).
  • Martin-Gayo, E.#, Cole, M.#, Kolb, K.E.#, Ouyang, Z., Cronin, J., Kazer, S.W., Lichterfeld, M., Walker, B.D., Yosef, N.*, Shalek, A.K.*, and Yu, X.G.*, “A Rational Framework for Modulating Ensemble Immune Behaviors Inspired by HIV-1 Elite Control,” Genome Biology, 19, 10 (2018).
  • 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.*, “Seq-Well: A Portable, Low-cost Platform for Single-Cell RNA-Seq of Low-Input Samples,” Nature Meth., 14, 395 (2017).
  • Tirosh, I. #, Izar, B. #, Prakadan, S.M., Wadsworth II, M.H., Tracy, D., Trombetta, J.J., Rotem, A., Rodman, C., Lian, C., Murphy, G., Fallahi-Sichani, M., Dutton-Regester, K., Lin, J.R., Cohen, O., Shah, P., Lu, D., Genshaft, A., Hughes, T.K., Ziegler, C.G.K., Kazer, S.W., Gaillard, A., Kolb, K.E., Villani, A.C., Johannessen, C.M., Andreev, A.Y., van Allen, E.M., Bertagnolli, M., Sorger, P.K., Sullivan, R.J., Flaherty, K.T., Frederick, D.T., Jané-Valbuena, J., Yoon, C.*, Rozenblatt-Rosen, O.*, Shalek, A.K.*, Regev, A.*, and Garraway, L.*, “Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq,” Science, 352, 189 (2016).

A full list of Professor Shalek’s publications can be found on his website.

Courses Taught

5.60 (5.601/5.602) – Fall 2014, Fall 2015, Fall 2016, Fall 2017, Fall 2018, Fall 2020, Spring 2022
Thermodynamics & Kinetics

5.64/HST.539 – Spring 2016, Spring 2017, Spring 2018, Spring 2019, Spring 2020, Spring 2021, Spring 2022
Frontiers of Interdisciplinary Science in Human Health and Disease