Alex K. Shalek

Alex K. Shalek, PhD

Principal Investigator


Member

Ragon Institute of MGH, MIT and Harvard

Associate Professor

IMES, Chemistry, and Koch Institute, MIT

Institute Member

Broad Institute of MIT and Harvard

Contact


617.324.5670

E25-348a

Visit Lab Website

Single-Cell Genomics, Systems Immunology

Research Overview

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.

Recognition and Media

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.

About

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.

Selected Publications

Seq-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 Methods, 14, 395 (2017)

Reduced 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)

Recovery of Paired T Cell Receptors from Massively-Parallel 3’ Single-Cell RNA-Seq Libraries Reveals Clonotypic Responses among Antigen-Activated T Cells

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)

Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics

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).

Integrated 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)

SARS-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)

Second 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)

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

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)

Lab Team

Sam Allon

Graduate Student

Josh Bromley

Graduate Student

Thomas Nok Hin Cheng

Undergraduate Student

Charles P. Couturier

Postdoctoral Fellow

Tyler Dao

Graduate Student

Riley Drake

Research Technician I

Elliot-Boblitt

Project Coordinator

Jeff Gahan

Jennyfer Galvez-Reyes

Research Technician I

Patricia Gao

Undergraduate Student

Alex Genshaft

Postdoctoral Fellow

Micayla George

Research Technician I

Brittany Goods

Postdoctoral Fellow

Travis Hughes

Graduate Student

Samira Ibrahim

Research Technician I

Tasneem Jivanjee

Research Technician I

Jasmin Joseph-Chazan

Graduate Student

Jim Kaminski

Postdoctoral Fellow

Kyle Kimler

Researcher

Kami Krista

Undergraduate Student

Conner Kummerlowe

Graduate Student

Ivy Liu

Graduate Student

Ben Mead

Postdoctoral Fellow

Vincent Miao

Graduate Student

Nolawit Mulugeta

Research Technician I

Andrew Navia

Graduate Student

Leonard Nettey

Graduate Student

Son Nguyen

Postdoctoral Fellow

Sarah Nyquist

Graduate Student

Sarah Quinn

Graduate Student

Adam Rubin

Postdoctoral Fellow

Daniela Russo

Bioinformatics Analyst

Evelyn Yuzhou Tong

Graduate Student

Nancy Tran

Lab Manager

Constantine Tzouanas

Graduate Student

Mike Vilme

Research Technician I

Dennis Wang

Undergraduate Student

Peter Winter

Postdoctoral Fellow

Melody Wu

Undergraduate Student

Carly Ziegler

Graduate Student

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