The Shalek Lab develops and applies broadly applicable experimental and computational platforms to understand and engineer immune responses in tissues. We employ a comprehensive, five-step approach, building innovative methodologies and leveraging them with partners around the world to facilitate deeper, more mechanistic inquiry into how cells drive tissue-level behaviors across the spectrum of human health and disease.
Biology
Cancer
Immunology
Microbiology
R&D
Technology
Alex K. Shalek
Ben Mead
Conner Kummerlowe
Ivy Liu
Manny Guzman
Sarah Ingabire
Sergio Triana
Walaa Kattan
High-throughput phenotypic screens using biochemical perturbations and high-content readouts are constrained by limitations of scale. To address this, we establish a method of pooling exogenous perturbations followed by computational deconvolution to reduce required sample size, labor and cost. We demonstrate the increased efficiency of compressed experimental designs compared to conventional approaches through benchmarking with a bioactive small-molecule library and a high-content imaging readout.
Computational Methods
Immunology
Infectious Disease
Alex K. Shalek
Josh Bromley
Sarah Nyquist
Th1 CD4+ T cells mediate protective antiMtb immunity across biological systems and organisms. Bromley, Ganchua, et al. demonstrate that CD4+ T cells regulate immune tone in TB granulomas and are necessary for immune recall and protection against reinfection. Following reinfection, CD4+ T cells facilitate the development of a growth restrictive niche via the induction of immuno-modulatory genes and cellular interaction networks.
Computational Methods
Infectious Disease
Alex K. Shalek
Andrew Navia
Carly Ziegler
Josh Bromley
José Ordovas-Montañes
Micayla George
Riley Drake
Sam Kazer
Vincent Miao
Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined.
Apr 07, 2025
MESA uses ecological theory to map cellular diversity and spatial patterns in tissues, offering new insights into disease progression. To understand what truly drives disease progression in tissues, scientists need more than just a snapshot of cells in isolation—they need to see where the cells are, how they interact, and how that spatial organization shifts […]
Oct 22, 2024
Novel method to scale phenotypic drug screening drastically reduces the number of input samples, costs, and labor required to execute a screen. Read the full article on MIT News.
Sep 16, 2024
Learn more about this collaborative work featuring Alex Shalek and a discovery that yields a potent immune response, which could be used to develop a potential tumor vaccine.