Alex K. Shalek

J. W. Kieckhefer Professor - IMES, Chemistry, and Koch Institute, MIT; Institute Member, Broad Institute; Member, Ragon Institute

Research Expertise

single-cell genomics

micro- and nanotechnology

infectious diseases

cancer

autoimmunity

About

Alex K. Shalek, PhD, is the J. W. Kieckhefer Professor in the Institute for Medical Engineering & Science and the Department of Chemistry, and an Extramural Member of The Koch Institute for Integrative Cancer Research at MIT. He is also an Institute Member of the Broad Institute, a Member of the Ragon Institute, an Assistant in Immunology at MGB, and an Instructor in Health Sciences & Technology at HMS. Dr. Shalek received his bachelor's degree *summa cum laude* from Columbia University and his Ph.D. from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). His lab’s research is directed towards the development and application of new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. Dr. Shalek and his work have received numerous honors including a NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, the Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), and an Alfred P. Sloan Research Fellowship in Chemistry, as well as the 2019-2020 Harold E. Edgerton Faculty Achievement Award at MIT and the 2020 HMS Young Mentor Award.

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Publications

Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets

Cell

2015

Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

Science

2014

Abstract 4380: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-sequencing

Cancer Research

2016

Faculty Opinions recommendation of SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

2020

The Human Cell Atlas: from vision to reality

Nature

2017

A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade

Cell

2018

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Cell

2019

Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity

Cell

2019

Systematic comparison of single-cell and single-nucleus RNA-sequencing methods

Nature Biotechnology

2020

Faculty Opinions recommendation of COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

2021

Prevention of tuberculosis in macaques after intravenous BCG immunization

Nature

2020

T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Cell

2018

Allergic inflammatory memory in human respiratory epithelial progenitor cells

Nature

2018

Building a high-quality Human Cell Atlas

Nature Biotechnology

2021

Faculty Opinions recommendation of Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

2020

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Cell

2021

Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer

Cell

2021

Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration

Nature Communications

2019

Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration

Cell Stem Cell

2019

Identification of a Master Regulator of Differentiation in Toxoplasma

Cell

2020

317 CYTOF ANALYSIS OF HUMAN COLON AND BLOOD REVEALS DISTINCT IMMUNE SIGNATURES OF ULCERATIVE COLITIS AND CROHN'S DISEASE

Gastroenterology

2020

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis

Nature

2019

Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies

Immunity

2020

Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells

Cell

2018

Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases

Nature Genetics

2023

Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection

Nature Medicine

2020

Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas

Nature Communications

2021

Systematic comparative analysis of single cell RNA-sequencing methods

Unknown Venue

2019

Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states

Unknown Venue

2020

Faculty Opinions recommendation of Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

2022

Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential

Cell

2021

Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity

Cell Reports

2020

Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation

Science Immunology

2021

High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity

Cell Reports

2021

Computational Methods for Single-Cell RNA Sequencing

Annual Review of Biomedical Data Science

2020

Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics

Cell

2020

A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases

Genome Medicine

2019

Expression of Foxp3 by T follicular helper cells in end-stage germinal centers

Science

2021

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8⁺ T cell repertoire upon viral exposure

Unknown Venue

2021

Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virus

Immunity

2019

Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

Science Translational Medicine

2019

IL-5Rα marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease

Journal of Allergy and Clinical Immunology

2020

Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer

Proceedings of the National Academy of Sciences

2019

Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth

JCI Insight

2017

Functional compensation precedes recovery of tissue mass following acute liver injury

Nature Communications

2020

SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues

SSRN Electronic Journal

2020

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Frontiers in Pharmacology

2021

The cellular architecture of the antimicrobial response network in human leprosy granulomas

Nature Immunology

2021

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells

Nature Communications

2019

Linking single-cell measurements of mass, growth rate, and gene expression

Genome Biology

2018

Regulation of X-linked gene expression during early mouse development by Rlim

eLife

2016

Deciphering the immunopeptidome in vivo reveals new tumour antigens

Nature

2022

Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8 ⁺ T cells drive gastrointestinal acute graft-versus-host disease

Science Translational Medicine

2021

Single cell profiling of COVID-19 patients: an international data resource from multiple tissues

Unknown Venue

2020

Highly Efficient, Massively-Parallel Single-Cell RNA-Seq Reveals Cellular States and Molecular Features of Human Skin Pathology

Unknown Venue

2019

Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease

Journal of Allergy and Clinical Immunology

2021

Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells

Journal of Experimental Medicine

2020

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients

PLOS Pathogens

2021

Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types

BMC Biology

2018

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Nature Communications

2018

A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers

Genome Biology

2018

Bioinformatics analysis of single-cell mRNA-seq of SARS-CoV-1 and SARS-CoV-2 infection compared to MERS-CoV from Sequence Read Archive (SRA) database reveals novel targets for therapies

Unknown Venue

2020

Induction of metabolic quiescence defines the transitional to follicular B cell switch

Science Signaling

2019

Seq-Well: A Sample-Efficient, Portable Picowell Platform for Massively Parallel Single-Cell RNA Sequencing

Methods in Molecular Biology

2019

A knockoff calibration method to avoid over-clustering in single-cell RNA-sequencing

Unknown Venue

2024

Comparative analysis of cell–cell communication at single-cell resolution

Nature Biotechnology

2023

Scalable nonparametric clustering with unified marker gene selection for single-cell RNA-seq data

Unknown Venue

2024

Glycan-costumed virus-like particles promote type 1 anti-tumor immunity

Unknown Venue

2024

Single-Cell RNA Sequencing Reveals That Adaptation of Human Aortic Endothelial Cells to Antiproliferative Therapies Is Modulated by Flow-Induced Shear Stress

Arteriosclerosis, Thrombosis, and Vascular Biology

2023

Recovery of Paired T Cell Receptors from Single-cell Seq-Well Libraries

Unknown Venue

2023

scRNA-Seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria

Unknown Venue

2023

Pro-inflammatory feedback loops define immune responses to pathogenic lentivirus infection

Unknown Venue

2023

NIAID workshop on T cell technologies

Nature Immunology

2023

Single-cell transcriptomics of staged oocytes and somatic cells reveal novel regulators of follicle activation

Reproduction

2022

Comparative analysis of cell-cell communication at single-cell resolution

Unknown Venue

2022

Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

JCI Insight

2021

Evolution and Diversity of Immune Responses during Acute HIV Infection

Immunity

2020

The Human Cell Atlas and equity: lessons learned

Nature Medicine

2020

Improved haplotype inference by exploiting long-range linking and allelic imbalance in RNA-seq datasets

Nature Communications

2020

Distribution and storage of inflammatory memory in barrier tissues

Nature Reviews Immunology

2020

Spatially-Resolved Live Cell Tagging and Isolation Using Protected Photoactivatable Cell Dyes

Unknown Venue

2020

TCR sequencing paired with massively parallel 3′ RNA-seq reveals clonotypic T cell signatures

Nature Immunology

2019

Recovery of Paired T Cell Receptors from Single-cell Seq-Well Libraries

Unknown Venue

2019

Reduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity

Unknown Venue

2017

Single-cell analyses to tailor treatments

Science Translational Medicine

2017

Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices

Nature Reviews Genetics

2017

Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput

Protocol Exchange

2017

Baring cellular souls

Science Translational Medicine

2017

Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput

Nature Methods

2017

A case of mistaken identity

Science Translational Medicine

2017

IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Cell

2017

A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages

Nature Communications

2016

A basic strategy for detecting CD8 T cell specificity

Science Translational Medicine

2016

Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion

Immunity

2016

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

Science

2016

Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression

Immunity

2016

Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM

Proceedings of the National Academy of Sciences

2016

Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction

Genome Biology

2016

On the right track

Science Translational Medicine

2016

Size no longer matters

Science Translational Medicine

2016

Speed kills

Science Translational Medicine

2016

Oct1 and OCA-B are selectively required for CD4 memory T cell function

Journal of Experimental Medicine

2015

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Cell

2015

Marrying microfluidics and microwells for parallel, high-throughput single-cell genomics

Genome Biology

2015

MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data

Genome Biology

2015

MERFISHing for spatial context

Trends in Immunology

2015

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Cell

2015

Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity

Cell

2015

Preparation of Single‐Cell RNA‐Seq Libraries for Next Generation Sequencing

Current Protocols in Molecular Biology

2014

Deconstructing transcriptional heterogeneity in pluripotent stem cells

Nature

2014

Heterogeneity in immune responses: from populations to single cells

Trends in Immunology

2014

Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells

Cell

2014

Single-cell RNA-seq reveals dynamic paracrine control of cellular variation

Nature

2014

Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL

Blood

2014

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

Nature Biotechnology

2014

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

Nature Biotechnology

2013

Dynamic regulatory network controlling TH17 cell differentiation

Nature

2013

Probing Enzymatic Activity inside Living Cells Using a Nanowire–Cell “Sandwich” Assay

Nano Letters

2012

Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells

Nature

2013

Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells

Cell

2013

Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia

Nano Letters

2012

Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits

Nature Nanotechnology

2012

Systematic Discovery of TLR Signaling Components Delineates Viral-Sensing Circuits

Cell

2011

Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

Proceedings of the National Academy of Sciences

2010

Photoinduced Interfacial Charging and “Explosion” of Monolayer Pentacene Islands

Nano Letters

2005

Education

Harvard University

PhD, Chemistry and Chemical Biology / May, 2011

Cambridge, Massachusetts, United States of America

Harvard University

AM, Chemistry and Chemical Biology / May, 2006

Cambridge, Massachusetts, United States of America

Columbia University

BA, Chemistry / May, 2004

New York, New York, United States of America

Experience

Broad Institute

Institute Member / July, 2019 — Present

Associate Member / July, 2014 — June, 2019

Postdoctoral Fellow - Regev Lab / June, 2011 — June, 2014

Massachusetts Institute of Technology

J. W. Kieckhefer Professor, Institute for Medical Engineering & Science and Department of Chemistry / July, 2023 — Present

Extramural Member of the Koch Institute / January, 2018 — Present

Core Member of the Institute for Medical Engineering & Science / July, 2014 — Present

Assistant Professor of Chemistry / July, 2014 — June, 2019

Associate Professor of Chemistry / July, 2019 — June, 2023

Massachusetts General Hospital

Assistant / July, 2014 — Present

Harvard-MIT Division of Health Sciences and Technology

Instructor / July, 2014 — Present

Ragon Institute

Associate Member / July, 2014 — June, 2018

Member / July, 2018 — Present

Harvard University

Postdoctoral Fellow - Park Lab / June, 2011 — June, 2014

Links & Social Media

Research Web Site

Shalek Lab - Chemistry, MIT

Shalek Lab - HST

Shalek Lab - Ragon Institute

Shalek Lab

Shalek Lab - IMES, MIT

ORCID

Research Web Site

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