Prof. Alex Shalek

J W Kieckhefer Professor in the Institute for Medical Engineering and Science and the Department of Chemistry
Director, Institute for Medical Engineering and Science (IMES)
Director of Health Innovation Hub
Extramural Member, Koch Institute for Integrative Cancer Research
Member, Ragon Institute
Institute Member, Broad Institute
Assistant in Immunology, Massachusetts General Hospital (MGH)
Instructor, Health Sciences and Technology, Harvard Medical School (HMS)

Assistant

Jeff Gahan
jgahan@mit.edu

Areas of Interest and Expertise

Nanobiotechology
Single Cells
Systems Biology
Microfluidics
Genomics
Immunology
Cellular Circuits
Synthetic Biology
Cancer
Molecular Biology
Chemical Biology
Proteomics
Modeling
Nanofabrication
Microfabrication
HIV
TB
Vaccines
Autoimmunity
Immunodeficiency
Mucosal Immunology
Precision Medicine
Tumor Immunology
Computational Biology

Research Summary

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 of 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.

Recent Work

  • Video

    4.4.23-Health-Shalek

    April 4, 2023Conference Video Duration: 36:38
    Does Cell State Matter in Cancer? 

    AI in LIfe Science 2018 - Alex Shalek

    December 4, 2018Conference Video Duration: 28:23

    Identifying and Rationally Modulating Cellular Drivers of Enhanced Immunity

    Immune homeostasis requires constant collaboration between a diverse and dynamic set of cell types. Within our immune tissues, distinct cellular subsets must work together to defend against pathogenic threats, maintain tolerance, and establish memory. While surveying multiple healthy individuals enables exploration of potential ensemble immune solutions, contrasts against outliers of health and disease can reveal deviations that underscore diagnostic, therapeutic, and prophylactic features of enhanced function or dysfunction. Here, I will discuss how we can leverage single-cell genomic approaches – and, in particular, single-cell RNA-Seq – to explore the extensive functional diversity among immune cells within and across individuals, and uncover, from the bottom-up, distinct cell types and states associated with improved immunity. Moreover, I will discuss emerging experimental and computational strategies for altering ensemble cellular responses through targeted intra- or extracellular induction of these preferred types and states.

    2018 MIT AI in Life Sciences and Healthcare Conference