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
Genomics
Immunology
Infectious Disease
Medicine
Andrew Navia
Carly Ziegler
Josh Bromley
José Ordovas-Montañes
Kyle Kimler
Micayla George
Riley Drake
Samira Ibrahim
Tasneem Jivanjee
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.
Dec 03, 2025
Nature Reviews Drug Discovery article: Phenotypic drug discovery screens offer physiologically relevant disease-linked readouts and account for polypharmacology. However, they are more complex than target-based screens and difficult to conduct at scale. Reporting in Science, DeMeo et al. apply transcriptome datasets as a proxy for cell phenotypes and design a deep learning framework to prioritize compounds […]
Oct 23, 2025
A deep-learning design sidesteps the need for time-consuming drug-screening. An artificial intelligence (AI) model trained on complex data from human cells could provide a shortcut in the race to develop new drugs1. The approach, published on 23 October in Science, builds on a trend that is sweeping the field of drug discovery: the use of AI to speed […]
Oct 02, 2025
Ankit Basak (Chemistry/IMES) Feature When Ankit Basak arrived at MIT for graduate school, he came with a broad, interdisciplinary background and a keen interest in developing new tools for biological research. Raised in Kolkata, India, Basak pursued an integrated BS-MS program at the Indian Institute of Science Education and Research (IISER) Kolkata, where he studied chemistry […]