Alex K. Shalek
Institute for Medical Engineering & Science and Department of Chemistry, MIT
Ragon Institute/ Broad Institute/ HMS/ MGH
Development and application of new technologies that facilitate understanding of how immune cells collectively perform systems-level functions in health and disease.
Research in the Shalek Lab is directed towards the development and application of new technologies that will facilitate 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” interactions (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.
Tirosh, I.#, Izar, B.#, Prakadan, S.M., Wadsworth II, M.H., Tracy, D., Trombetta, J.J., Lu, D., Rotem, A., Lian, C., Murphy, G., Cohen, O., van Allen, E., Bertagnolli, M., Genshaft, A., Hughes, T.K., Ziegler, C.G.K., Kazer, S.W., Gaillard, A., Kolb, K.E., 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).
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).
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).
Massachusetts Institute of Technology
Cambridge, MA 02139