Biography

Alex K. 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. To date, his interdisciplinary research has focused on developing and utilizing nanoscale manipulation and measurement technologies to understand how small components (molecules, cells) drive systems of vast complexity (cellular responses, population behaviors). As a graduate student, Alex developed arrays of nanowires as cellular-scale syringes and electrochemical probes and used them to study how biochemical perturbations alter cellular responses en masse. While these studies yielded important insights, they also highlighted how population-level measurements can mask underlying differences between individual cells in these systems. As an alternative approach, as a postdoctoral fellow, he developed a strategy that uses single-cell RNA-Seq to identify distinct cell states and circuits from the natural variation that exists between seemingly identical cells. Since then, he has dramatically increased the throughput and control of his methods with microfluidic cell preparation and isolation schemes. This has enabled him to uncover how responses to pathogens are structured within dendritic cell (DC) populations, and how cell-to-cell variability arises from intra- and inter-cellular regulatory circuits in healthy and diseased states, as well as to explore the causes and consequences of cellular heterogeneity in additional systems of interest.

Publications

Science Forum: The Human Cell Atlas
  • Regev A. et al.,
  • eLife,
  • 2017
  • Computational Methods
  • Technology
  • Cell Atlas
  • Immunology
  • Genomics
  • Biology
  • Medicine
  • Alex K. Shalek
Reduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity
  • Jose Ordovas-Montanes et al.,
  • BioRxiv,
  • 2017
  • Cell Atlas
  • Medicine
  • Immunology
  • José Ordovas-Montañes
  • Sarah Nyquist
  • Marc Wadsworth
  • Travis Hughes
  • Sam Kazer
  • Alex K. Shalek
IFNγ-Dependent Tissue-Immune Homeostasis is Co-opted in the Tumor Microenvironment
  • Nirschl et al.,
  • Cell,
  • 2017
  • Immunology
  • Genomics
  • Cancer
  • Jay Prakadan
  • Alex K. Shalek
Scaling by shrinking: empowering single-cell ‘omics’ with microfluidic devices
  • Prakadan et al.,
  • Nature Reviews Genetics,
  • 2017
  • Genomics
  • Technology
  • Jay Prakadan
  • Alex K. Shalek
Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput
  • Gierahn et al.,
  • Nature Methods,
  • 2017
  • R&D
  • Travel
  • Genomics
  • Chemistry
  • Technology
  • Marc Wadsworth
  • Travis Hughes
  • Alex K. Shalek
Circulating CXCR5+CXCR3+PD-1lo Tfh-like Cells in HIV-1 Controllers with Neutralizing Antibody Breadth
  • Martin-Gayo et al.,
  • JCI Insight,
  • 2017
  • Infectious Disease
  • Immunology
  • Biology
  • Kellie Kolb
  • Alex K. Shalek
Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion
  • Ranasinghe et al.,
  • Immunity,
  • 2016
  • Biology
  • Infectious Disease
  • Immunology
  • Sam Kazer
  • Alex K. Shalek
Regulation of X-linked gene expression during early mouse development by Rlim
  • Wang et al.,
  • eLife,
  • 2016
  • Biology
  • Genomics
  • Alex K. Shalek
Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction
  • Genshaft et al.,
  • Genome Biology,
  • Genomics
  • R&D
  • Technology
  • Biology
  • Chemistry
  • Alex Genshaft
  • Jay Prakadan
  • Carly Ziegler
  • Alex K. Shalek
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
  • Tirosh et al.,
  • Science,
  • 2016
  • Cancer
  • Genomics
  • Biology
  • Medicine
  • Jay Prakadan
  • Marc Wadsworth
  • Alex Genshaft
  • Travis Hughes
  • Carly Ziegler
  • Sam Kazer
  • Aleth Gaillard
  • Kellie Kolb
  • Alex K. Shalek
Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM
  • Wong et al.,
  • PNAS,
  • 2016
  • Genomics
  • Chemistry
  • Technology
  • Sam Kazer
  • Aleth Gaillard
  • Alex K. Shalek
Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression
  • Kløverpris et al.,
  • Immunity,
  • 2016
  • Biology
  • Genomics
  • Immunology
  • Infectious Disease
  • Sam Kazer
  • Alex K. Shalek
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages
  • Kimmerling et al.,
  • Nat. Commun.,
  • 2016
  • Biology
  • R&D
  • Genomics
  • Immunology
  • Technology
  • Alex Genshaft
  • Sam Kazer
  • Alex K. Shalek
Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity
  • Gaublomme et al.,
  • Cell,
  • 2015
  • Genomics
  • Immunology
  • Biology
  • Alex K. Shalek
Oct1 and OCA-B are selectively required for CD4 memory T cell function
  • Shakya et al.,
  • J. Exp. Med.,
  • 2015
  • Immunology
  • Genomics
  • Biology
  • Alex K. Shalek
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses
  • Avraham et al.,
  • Cell,
  • 2015
  • Microbiology
  • Technology
  • Immunology
  • Infectious Disease
  • Biology
  • Genomics
  • Alex K. Shalek
Marrying microfluidics and microwells for parallel, high-throughput single-cell genomics
  • Wadsworth II et al.,
  • Genome Biology,
  • 2015
  • Genomics
  • R&D
  • Technology
  • Marc Wadsworth
  • Travis Hughes
  • Alex K. Shalek
Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets
  • Macosko et al.,
  • Cell,
  • 2015
  • Genomics
  • R&D
  • Technology
  • Alex K. Shalek
Deconstructing transcriptional heterogeneity in pluripotent stem cells
  • Kumar et al.,
  • Nature,
  • 2014
  • Genomics
  • Biology
  • Alex K. Shalek
Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL
  • Wang et al.,
  • Blood,
  • 2014
  • Genomics
  • Cancer
  • Alex K. Shalek
Preparation of Single-Cell RNA-Seq Libraries for Next Generation Sequencing
  • Trombetta et al.,
  • Current Protocols in Molecular Biology,
  • 2014
  • Technology
  • R&D
  • Alex K. Shalek
Single-cell RNA-seq reveals dynamic paracrine control of cellular variation
  • Shalek et al.,
  • Nature,
  • 2014
  • Biology
  • Genomics
  • Alex K. Shalek
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
  • Patel et al.,
  • Science,
  • 2014
  • Genomics
  • Cancer
  • Alex K. Shalek
Heterogeneity in immune responses: from populations to single cells
  • Satija et al.,
  • Trends in Immunology,
  • 2014
  • Genomics
  • Immunology
  • Technology
  • Alex K. Shalek
Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells
  • Suvà et al.,
  • Cell,
  • 2014
  • Biology
  • Genomics
  • Cancer
  • Alex K. Shalek
Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer
  • Lohr et al.,
  • Nature Biotechnology,
  • 2014
  • Cancer
  • Biology
  • Genomics
  • Alex K. Shalek
Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells
  • Shalek et al.,
  • Nature,
  • 2013
  • Biology
  • Immunology
  • Genomics
  • Alex K. Shalek
Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
  • Gifford et al.,
  • Cell,
  • 2013
  • Genomics
  • Biology
  • Alex K. Shalek
Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli
  • Gat-Viks et al.,
  • Nature Biotechnology,
  • 2013
  • Immunology
  • Biology
  • Alex K. Shalek
Dynamic regulatory network controlling TH17 cell differentiation
  • Yosef et al.,
  • Nature,
  • 2013
  • Immunology
  • Genomics
  • Biology
  • Alex K. Shalek
Probing Enzymatic Activity inside Living Cells Using a Nanowire−Cell “Sandwich” Assay
  • Na et al.,
  • Nano Letters,
  • 2013
  • Immunology
  • Biology
  • Technology
  • Chemistry
  • Alex K. Shalek
Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits
  • Robinson et al.,
  • Nature Nanotechnology,
  • 2012
  • Chemistry
  • Biology
  • Technology
  • Alex K. Shalek
Systematic Discovery of TLR Signaling Components Delineates Viral-Sensing Circuits
  • Chevrier et al.,
  • Cell,
  • 2011
  • Infectious Disease
  • Genomics
  • Immunology
  • Alex K. Shalek
Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells
  • Shalek et al.,
  • PNAS,
  • 2010
  • R&D
  • Physics
  • Technology
  • Genomics
  • Chemistry
  • Alex K. Shalek
Photoinduced Interfacial Charging and “Explosion” of Monolayer Pentacene Islands
  • Chen L. et al.,
  • Nano Lett,
  • 2005
  • Technology
  • R&D
  • Chemistry
  • Physics
  • Alex K. Shalek