Assistant Professor. Alex Shalek
MIT, Cambridge, USA
Please note programme is co-sponsored by Fluidigm, Millennium Science, The Maurice Wilkins Centre, The Malaghan Institute and Victoria University of Wellington
Dr Shalek’s work has been multidisciplinary, drawing from chemistry, physics, and nanotechnology to conceive of new high-resolution tools for the investigation and manipulation of cells and cell populations. From embryonic stem cells to immune cells through tumour cells and neurons, Dr Shalek and collaborators have been at the cutting edge of understanding fine, single-cell transcriptional processes and variability that until recently were only observable at the population level.
This has forced the revision of some ingrained pre-conceptions and mental constructs used, amongst other fields, in immunology. Indeed, as their single-cell transcriptomics experiments have shown, immune cells present a much higher diversity of responses to stimuli than previously thought–be it in the fraction of responding cells, the level of response, or the temporal and spatial dynamics thereof. As such, even the most “pure” cell-surface-marker-sorted population of immune cells may potentially present wildly varying reactions to immune challenges, a heterogeneity that is important at the system level to ensure rapid and robust responses (or non-responses) to stimuli. Even a tiny minority sub- population can drive a transcriptional response strong enough to show up at the population level.
Much like the precociously-reacting bone-marrow-derived dendritic cells that they have described as reacting to bacteria-derived stimuli, Dr Shalek and colleagues are the flag-earers for these new single-cell technologies which, despite the irrelative immaturity, already show exciting and paradigm-shifting results, and which also serve as an important reminder of the care that must be taken when interpreting findings at the cell population level. Soon, the trees will no longer hide the forest.
Dr Shalek has recently been appointed as assistant professor at the MIT Chemistry Department, where he will continue his work on new nanotech and chemical biology technologies that will aid in understanding cell heterogeneity, cell-to-cell interactions and cell ensemble decision-making, in both healthy and diseased states. This will lead to a more integrated view on how cells collectively perform systems-level functions.
Selected publications in the last 3 years
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).
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).
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).
Shalek, A. K., Satija, R., Adiconis, X., Gertner, R. S., Gaublomme, J. T., Raychowdhury, R., Schwartz, S., Yosef, N., Malboeuf, C., Gnirke, A., Goren, A., Hacohen, N., Levin, J., Park, H. & Regev, A. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 498, 236, (2013).
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).
Suva, 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).
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).
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).
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).