Shalek

Alex K. Shalek, PhD

Lab Info:

Principal Investigator: Alex K. Shalek, PhD

Office/Location: MIT E25-526B

Phone: (617) 324-5670

Email: shalek@mit.edu

Category: Associate Members

Dr. Alex K. Shalek is the Pfizer-Laubach Career Development Associate 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 Institute, an Institute Member of the Broad Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at Harvard Medical School.

 

Dr. Shalek’s 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. 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, Dr. Shalek 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, 2012Yosef 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, Dr. Shalek 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 arise from intra- and intercellular regulatory circuits (Shalek et al, Nature, 2014). Later, as an independent investigator, he helped realize massively parallel, reverse-emulsion– and nanowell-based strategies (Drop-Seq, Seq-Well, respectively) to explore the cellular composition of complex tissues like 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, Dr. Shalek and his team have leveraged these and additional approaches (Genshaft et al, Genome Biology, 2016Kimmerling 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, 2014Tirosh et al, Science, 2016), HIV-1 infection (Kløverpris et al, Immunity, 2016Ranasinghe et al, Immunity, 2016), and allergy (Ordovas-Montanes et al, Nature, 2018).

 

Dr. Shalek is the recipient of numerous awards, including the NIH Director’s New Innovator Award, the Searle Scholar Award, and the Alfred P. Sloan Research Fellowship in Chemistry. He is also a Pew-Stewart Scholar for Cancer Research and a Beckman Young Investigator.

 

Additionally, Dr. Shalek is a coleader of the Human Equity Working Group of the Human Cell Atlas (HCA) Project and an associate editor for Science Advances.

 

Dr. Shalek received an undergraduate degree in chemical physics from Columbia College and a PhD in chemical physics from Harvard University under the guidance of Hongkun Park. He completed postdoctoral training at Harvard University and the Broad Institute with Hongkun Park and Aviv Regev.

 

Visit Dr. Shalek’s lab website:   www.shaleklab.com

 

Research Interests

Research in the Shalek group is directed towards the development and application of new technologies that will facilitate a better understanding of how cells collectively perform systems-level functions in healthy and diseased states.”. With respect to technology development, the group is leveraging recent advances in nanotechnology and chemical biology to establish a host of core, cross-disciplinary platforms that will collectively enable them to extensively profile and precisely control cells and their interactions within the context of complex systems.

 

With respect to biological applications, the group is focusing on how cellular heterogeneity and cell-to-cell communication drive ensemble-level decision-making in the immune system, with an emphasis on “two-body” interaction (e.g., host cell-virus interactions, innate immune control of adaptive immunity, tumor infiltration by immune cells). The goal is to not only provide broadly applicable experimental tools but also help transform the way in which we think about single cells, cell-cell interactions, diseased cellular states and therapeutics so as to create a new paradigm for understanding and designing systems-level cellular behaviors in multicellular organisms.

Publications

17. Trombetta, J.J. *, Gennert, D. *, Lu, D. *, Satija, R., Shalek, A.K., and Regev, A., “Preparation of Single Cell RNA-Seq Libraries for Next Generation Sequencing,” Current Protocols in Molecular Biology, 107, 4.22.1 (2014).

 

16. Patel, A.P.*, Tirosh, I*, Trombetta, J.J., Shalek, A.K., Gillespie, S.M., Wakimoto, H., Cahill, D.P., Nahed, B.V., Curry, W.T., Martuza, R.L., Louis, D.N., Rosenblatt-Rosen, O., Suvà, M.L., Regev, A., and Bernstein, B.E., “Single Cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma,” Science, 344, 1396 (2014).

 

15. 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).
14. Wang, L., Shalek, A.K., Lawrence, M., Ding, R., Gaublomme, J.T., Pochet, N., Stojanov, P., Sougnez, C., Shukla, S., Stevenson, K.E., Zhang, W., Wong, J., Sievers, Q.L., Macdonald, B., Vartanov, A.R., Goldstein, N.R., Sutton, A., Neuberg, D., Gabriel, S., He, X., Langer, E., Hacohen, N., Regev, A., Getz, G., Brown, J.R., Park, H., and Wu, C.J., “Somatic Mutation as a Mechanism of Wnt/β-Catenin Pathway Activation in CLL,” Blood, Epub ahead of print (2014).

 

13. Lohr, J.G., Adalsteinsson, V.A., Cibulskis K, Choudhury, A.D., Rosenberg, M., Cruz-Gordillo, P. Francis, J., Zhang, C.Z., Shalek, A.K., Satija, R., Trombetta, J.J., Lu, D., Tallapragada, N., Tahirova, N., Kim, S., Blumenstiel, B, Sougnez, C., Lowe, A., Wong, B., Auclair, D., Van Allen, E.M., Nakabayashi, M., Lis, R.T., Lee, G.S.M., Li, T., Chabot, M.S., Ly, A., Taplin, M.E., Clancy, T.E., Loda, M., Regev, A., Meyerson, M., Hahn, W.C., Kantoff, P.W., Golub, T.R., Getz, G., Jesse S. Boehm, J., Love, J.C., “Whole exome sequencing of CTCs as a window into metastatic prostate cancer,” Nature Biotechnology, 32, 479 (2014).

 

12. Satija, R., and Shalek, A.K., “Heterogeneity in Immune Responses – From Populations to Single Cells,” Trends in Immunology, 5, 219 (2014).

 

11. Suvà, M. *, Rheinbay, E.*, Gillespie, S.M., Patel, A.P., Chi, A.S., Riggi, N., Wakimoto, H., Rabkin, S.D., Matuza, R.L., Rivera, M.N., Rossetti, N., Beik, S., Kasif, S., Wortman, I., Shalek, A.K., Rozenblatt-Rosen, O., Regev, A., Louis, D.N., and Bernstein, B.E., “Reconstructing and Reprogramming the Developmental Hierarchy of Glioblastoma,” Cell, 157, 580 (2014).

 

10. 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).

 

9. 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)

 

8. Gifford, C.A., Ziller, M.J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A.K., Kelley, D.R., Shishkin, A.A., Issner, R., Zhang, X., Coyne, M., Fostel, J.L., Holmes, L., Meldrim, J., Guttman, M., Epstein, C., Park, H., Kohlbacher, O., Rinn, J., Gnirke, A., Lander, E.S., Bernstein, B.E., and Meissner, A., “Transcriptonal and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells,” Cell, 153, 1149 (2013).

 

7. Gat-Viks, I., Chevrier, N., Wilentzik, R., Eisenhaure, T. Raychowdhury, R., Steuerman, Y., Shalek, A.K., Hachohen, N., Amit,, I., and Regev, A., “Deciphering Molecular Circuits from Genetic Variation Underlying Transcriptional Responsiveness to Stimuli,” Nature Biotech., 31, 342 (2013).

 

6. Na, Y.R., Kim, S.Y., Gaublomme, J.T., Shalek, A.K., Jorgollia, M., Park, H. and Yang, E.G., “Probing Enzymatic Activity inside Living Cells Using a Nanowire−Cell “Sandwich” Assay,” Nano Lett., 13, 153 (2013).

 

5. Shalek, A.K.*, Gaublomme, J.T.*, Wang, L., Yosef, N., Chevrier, N., Andersen, M.S., Robinson, J.T., Pochet, N., Neuberg, D., Gertner, R.S., Amit, I., Brown, J.R., Hacohen, N., Regev, A., Wu, C.J., and Park, H., “Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia,” Nano Lett. 12, 6498 (2012).

 

4. Robinson, J.T., Jorgolli, M., Shalek, A.K., Yoon, M.H., Gertner, R.S., and Park, H., “Vertical Nanowire Electrode Arrays as a Scalable Platform for Intracellular Interfacing to Neuronal Circuits,” Nature Nanotech. 7, 180 (2012).

 

3. Chevrier, N., Mertins, P., Artyomov, M.N., Shalek, A.K., Iannacone, M., Ciaccio, M.F., Gat-Viks, I., Tonti, E., DeGrace, M.M., Clauser, K.R., Garber, M., Eisenhaure, T.M., Yosef, N., Robinson, J.T., Sutton, A., Andersen, M.S., Root, D.E., von Andrian, U., Jones, R.B., Park, H., Carr, S.A., Regev, A., Amit, I., and Hacohen, N. “Systematic Discovery of TLR Signaling Components Delineates Viral-Sensing Circuits,” Cell 147, 853 (2011).

 

2. Shalek, A.K., Robinson, J.T., Karp, E.S., Lee, J.S., Ahn, D.R., Yoon, M.H., Sutton, A., Jorgoli, M., Gertner, R.S., Gujral, T.S., MacBeath, G., Yang, E.G., and Park, H., “Vertical Silicon Nanowires as a Universal Platform for Delivering Biomolecules into Living Cells,” Proc. Natl. Acad. Sci. U. S. A. 107, 1870 (2010).

 

1. Chen L., Cherniavskaya, O., Shalek, A.K., and Brus, L., “Photoinduced Interfacial Charging and “Explosion” of Monolayer Pentacene Islands,” Nano Lett. 5, 2241 (2005).


 

Laboratory Staff