Development and application of new technologies that facilitate understanding of how immune cells collectively perform systems-level functions in health and disease.

The interdisciplinary research in the Shalek Lab aims to create and implement new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. This 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, we couple genomics, chemical biology, and nanotechnology to establish accessible, broadly-applicable cross-disciplinary platforms that enable us and others to profile and control cells and their interactions within complex multicellular systems. 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 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.

Selected Publications:

Gideon, H^#, Hughes, T.K.^#, Wadsworth, M.H., Tu, A.A., Gierahn, T.M., Hopkins, F.F., Wei, J.-R., Kummerlowe, C., Grant, N.L., Nargan, K., Phuah, J., Borish, H.J., Maiello, P., White, A.G., Ganchua, S.K.C., Myers, A., Ameel, C.L., Cochran, C.T., Nyquist, S.K., Peters, J.M., Tomko, J.A., Frye, L.J., Rosenberg, J.M.,  Shih, A., Chao, M., Scanga, C.A., Ordovas-Montanes, J., Berger, B., Mattila, J.T., Madansein, R., Love, J.C., Bryson, B., Lin, P.L., Leslie, A., Behar, S.M., Flynn, J.L^*, Fortune, S.M.^*, and Shalek, A.K.^*, “Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control,” Immunity, 55, 1 (2022).

Raghavan, S.^#, Winter,^,S.^#, Navia, A.W.^#, Williams, H.L., DenAdel, A., Kalekar, R.L., Galvez-Reyes, J., Lowder, K.E., Mulugeta, N., Raghavan, M.S., Borah, A.A., Väyrynen, S.A., Costa, A.D., Ng, R.W.S., Wang, J., Reilly, E., Ragon, D., Brais, L.K., Jaeger, A.M., Spurr, L.F., Li, Y.Y., Cherniak, A.D., Wakrio, I., Rotem, A., Johnson, B.E., McFarland, J.M., Sicinska, E., Jacks, T., Clancy, T.E., Perez, K., Rubinson, D.A., Ng, K., Cleary, J.M., Crawford, L., Manalis, S.R., Nowak, J.A., Wolpin, B.M.^*, Hahn, W.C.^*, Aguirre, A.J.^*, and Shalek, A.K.^*, “Transcriptional subtype-specific microenvironmental crosstalk and tumor cell plasticity in metastatic pancreatic cancer,” Cell, 184 6119 (2021); bioRxiv 2020.08.25.256214.

Ziegler, C.G.K.^#, Miao, V.N.^#, Owings, A.H.^#, Navia, A.W.^#, Tang, Y.^#, Bromley, J.D.^#, Lofty, P., Sloan, M., Laird, H., Williams, H.B., George, M., Drake, R.S., Christian, T., Parker, A., Sindel, C.B., Burger, M.W., Pride, Y., Hasan, M., Abraham, G.E., Senitko, M., Robinson, T.O.,Shalek, A.K.^*, Glover, S.C.^*, Horwitz, B.H.^*, and Ordovas-Montanes, J.^*, “Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19,” Cell,  184 4713 (2021).

Huang, S.^#, Ziegler, C.G.K.^#, Austin, J., Mannoun, N., Ordovas-Montanes, J., Vukovic, M., Shalek, A.K.^* and Von Andrian, U.^*, “Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential.” Cell, 184, 441 (2021).

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.^*, “Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics,” Cell, 183, 1 (2020).

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.^*, “Second Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies,” Immunity, 53, 878 (2020).

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, “SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues,” Cell, 181, 1016 (2020).