Immunology Faculty Member - Alex Shalek, PhD

Alex Shalek, PhD

Associate Member, Ragon Institute of MGH, MIT, and Harvard




Massachusetts Institute of Technology
77 Massachusetts Ave
Bldg E25-348a
Cambridge, MA 02139
Tel: 617-324-5670
Email: shalek@mit.edu
Visit my lab page here.



TITLE(S)
· Pfizer-Laubach Career Development Assistant Professor, MIT
· Core Member, Institute for Medical Engineering and Science, MIT
· Assistant Professor, Chemistry, MIT
· Extramural Member, The Koch Institute for Integrative Cancer Research, MIT
· Associate Member, Ragon Institute of MGH, MIT, and Harvard
· Associate Member, Broad Institute of MIT and Harvard
· Assistant in Immunology, MGH
· Instructor, Health Sciences and Technology, HMS

BIO
Alex K. Shalek is currently the Pfizer-Laubach Career Development Assistant Professor at MIT, as well as a Core Member of the Institute for Medical Engineering and Science (IMES), an Assistant Professor of Chemistry, and an Extramural Member of The Koch Institute for Integrative Cancer Research. He is also an Associate Member of the Ragon and Broad Institutes, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. His research is directed towards the development and application of new technologies that facilitate understanding of how cells collectively perform systems-level functions in healthy and diseased states. Alex received his bachelor’s degree summa cum laude from Columbia University and his PhD from Harvard University in chemical physics under the guidance of Hongkun Park. To date, his interdisciplinary research has focused on developing and utilizing nanoscale manipulation and measurement technologies to understand how small components (molecules, cells) drive systems of vast complexity (cellular responses, population behaviors). As a graduate student, Alex developed arrays of nanowires as cellular-scale syringes and electrochemical probes (Shalek et al, PNAS, 2010Robinson et al, Nature Nanotechology, 2012) and used them to study how biochemical perturbations alter cellular responses en masse (Chevrier et al, Cell, 2011Shalek et al, Nano Letters, 2012;  Yosef et al, Nature, 2013). While these studies yielded important insights, they also highlighted how population-level measurements can mask underlying differences between individual cells. In recognition of this, as a postdoctoral fellow, Alex developed an alternative approach that uses single-cell RNA-Seq to identify distinct cell states and circuits from the natural variation that exists between cells (Shalek et al, Nature, 2013). He then utilized microfluidic cell preparation and isolation schemes to discover how cell-to-cell variability in an immune response can arises from intra- and intercellular regulatory circuits (Shalek et al, Nature, 2014), and, as an independent investigator, helped realize massively parallel, reverse-emulsion- and nanowell-based strategies (Drop-Seq, Seq-Well, respectively) to explore the cellular composition of the retina (Macosko et al, Cell, 2015) and make single-cell RNA-Seq of low-input clinical specimens globally feasible (Gierahn et al, Nature Meth., 2017), respectively. In parallel, Alex and his team has leveraged these and additional approaches (Genshaft et al, Genome Biology, 2016; Kimmerling et al, Nature Commun., 2016) to help characterize the causes and consequences of cellular heterogeneity in additional systems of interest, such as cancer (Lohr et al, Nature Biotechnology, 2014Patel et al, Science, 2014; Tirosh et al, Science, 2016) and HIV-1 infection (Kløverpris et al, Immunity, 2016; Ranasinghe et al, Immunity, 2016).

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

SELECTED AWARDS/SOCIETIES
· 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

RESEARCH
Research in the Shalek Lab is directed towards the creation and implementation of new technologies to understand how cells collectively perform systems-level functions in healthy and diseased states. To examine the rules that govern ensemble cellular behaviors, we employ a comprehensive, five-step approach: first, we identify the fundamental elements that comprise our systems; second, we decipher the salient characteristics that differentiate each element; third, we explore how environmental signals impact the molecular computations each element makes; fourth, we examine how direct interactions between elements influence each other; and, finally, we investigate how the foregoing factors cooperatively drive ensemble phenomena. At each step, as we face technical limitations and pressing biological needs, we develop and apply innovative methodologies to empower a deeper, more mechanistic inquiry. Our technology development leverages recent advances in genomics, chemical biology, and nanotechnology to establish cross-disciplinary platforms for in-depth profiling and precise manipulation of cells and their interactions. Examples include microdevices for massively-parallel single-cell genomics, strategies for simultaneously measuring diverse cellular variables, microfluidic tools for controlling the cellular microenvironment, and approaches for engineering and profiling cell-cell interactions. Our biological applications focus on the roles of cellular heterogeneity and cell-to-cell communication in driving immune responses. Current studies examine how: innate and adaptive immune cells coordinate balanced responses to environmental changes; host cell-pathogen interactions evolve across time and tissues during HIV-1 and M. Tuberculosis infection; and, tumor cells evade immune responses. Overall, our goal is to realize broadly-applicable experimental and computational platforms to uncover common cellular motifs that inform healthy and diseased immune responses. Using this information, we aim to help transform how the community thinks about single cells, cell-cell interactions, diseased tissues and processes, and therapeutics to create a new paradigm for understanding and designing systems-level multicellular behaviors.



Last Update: 6/18/2018



Publications

· 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).
· Macosko, E.Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A.R., Kamitaki, N., Martersteck, E.M., Trombetta, J.J., Weitz, D.A., Sanes, J.R., Shalek, A.K., Regev, A., and McCarroll, S.A., “Genome-wide expression profiling of thousands of individual cells using nanoliter droplets,” Cell, 161, 1202 (2015).
· Shalek, A.K.#, Satija, R.#, Shuga, J.#, Trombetta, J.J., Lu, D., Gennert, D., Chen, P., Gertner, R.S., Gaublomme, J.T., Yosef, N., Schwartz, S., Fowler, B., Weaver, S., Wang, J., Wang, X., Ding, R., Raychowdhury, R., Friedman, N., Hacohen, N., Park, H.*, May, A.P.*, and Regev, A.*, “Large-Scale Single-Cell RNA-Seq Reveals Strategies for Regulating Cell-to-Cell Dynamic Variability through Paracrine Signaling,” Nature, 510, 363 (2014).
· Shalek, A.K.#, Satija, R.#, Adiconis, X., Gertner, R.S., Gaublomme, J.T., Raychowdhury, R., Schwartz, S., Yosef, N., Malboeuf, C., Lu, D., Trombetta, J.J., Gennert, D., Gnirke, A., Goren, A., Hacohen, N., Levin, J.Z., Park, H., and Regev, A., “Single-Cell Transcriptomics Reveals Bimodality in Expression and Splicing in Immune Cells,” Nature, 498, 236 (2013).
· Yosef, N.#, Shalek, A.K.#, Gaublomme, J.T.#, Jin, H., Lee, Y., Awasthi, A., Wu, C., Karwacz, K., Xiao, S., Jorgolli, M., Gennert, D., Satija, R., Shakya, A., Lu, D.Y., Trombetta, J.J., Pillai, M., Ratcliffe, P.J., Coleman, M.L., Bix, M., Tantin, D., Hongkun Park, H., Kuchroo, V.K., and Regev, A., “Dynamic Regulatory Network Controlling Th17 Cell Differentiation,” Nature, 496, 461 (2013).



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