Alex K. Shalek

Alex Shalek
Alex Shalek, August 2019
Born(1981-12-18)December 18, 1981
Alma materColumbia University
Harvard University
AwardsJ. W. Kieckhefer Professorship (2023-current)
Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (2021)
Harold E. Edgerton Faculty Achievement Award, MIT (2020)
Pew Charitable Trust Pew-Stewart Scholar (2018)
Alfred P. Sloan Foundation Sloan Research Fellow (2018)
Searle Scholars Program (2015)
Beckman Young Investigators Award (2015)
NIH Director's New Innovator Award (2015)
Scientific career
InstitutionsMassachusetts Institute of Technology
Broad Institute
Koch Institute for Integrative Cancer Research
Ragon Institute
Mass General Hospital
Harvard Medical School
Doctoral advisorHongkun Park
Websitewww.shaleklab.com

Alex K. Shalek, a biomedical engineer, is the Director of the Institute for Medical Engineering and Science (IMES) and the J. W. Kieckhefer Professor in IMES and the Department of Chemistry at the Massachusetts Institute of Technology. He is an Extramural Member of the Koch Institute for Integrative Cancer Research at MIT. Additionally, he is a Member of the Ragon Institute, an Institute Member of the Broad Institute, an Assistant in Immunology at Massachusetts General Hospital, and an Instructor in Health Sciences and Technology at Harvard Medical School. The multi-disciplinary research of the Shalek Lab aims to create and implement broadly-applicable methods to study and engineer cellular responses in tissues, to drive biological discovery and improve prognostics, diagnostics, and therapeutics for autoimmune, infectious, and cancerous diseases. Shalek and his lab are best known for their work in single-cell genomics and for studying a number of devastating, but difficult to study, human diseases with partners around the world.[1]

Education and previous research

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Shalek received his B.A. summa cum laude in 2004 from Columbia University where he studied chemical physics as a John Jay Scholar with Richard Bersohn and Louis Brus. He then performed graduate work in chemical physics developing arrays of nanowires as cellular "syringes" and electrochemical probes under the direction of Hongkun Park at Harvard University.[2] After, as a postdoctoral fellow, under the direction of Park and Aviv Regev at the Broad Institute, Shalek helped pioneer single-cell patterns in cellular responses to study how cells respond differently to the same condition, showing that genome-wide gene expression covariation across cells could be used to define cellular types and states, their internal "circuitry", from the “bottom-up”.[3][4][5][6]

As an independent investigator, Shalek and his lab have helped scale and simplify single cell genomics to study complex, low-input clinical specimens around the world.[7][5][8] In parallel, they have used these and other approaches [8][9][10][11][12][13][14][excessive citations] to help examine the causes and consequences of cellular heterogeneity across cancers,[15][16][17][18][19] infectious diseases,[5][8][9][10][20][21][22][23][24][25][26][27][excessive citations] and inflammation.[28][29][30]

Ongoing research

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Current work in the Shalek Lab includes both the development of broadly enabling technologies as well as their application to characterize, model, and control multicellular systems. With respect to technology development, the lab brings together areas of research in genomics, chemical biology, and nanotechnology to establish accessible approaches to profile and control cells and their interactions.

In addition to these tools with the global research community,[31] the lab is applying them to dissect human diseases, like COVID-19,[32][33] methodically linking cellular features and clinical observations. Major areas of focus include how: immune cells coordinate balanced responses to environmental stresses;[28][29][8][34] host cell-pathogen interactions evolve during infection;[8][9][10][21][22][23][26][excessive citations] and, tumor cells evade therapeutic treatment and natural immunity.[15][17][18][19][25][35]

From these observations and those of others, the lab aims to understand how disease alters tissue function at the cellular level and realize therapeutic and prophylactic interventions to reestablish or support human health.

Select honors and awards

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  • J. W. Kieckhefer Professorship, 2023 – current
  • Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), 2021
  • 2019-20 Harold E. Edgerton Faculty Achievement Award 2020[36]
  • Young Mentor Award, Harvard Medical School, 2020[37]
  • Pew-Stewart Scholar, Pew Charitable Trust Charitable Trust, 2018 – 2022[38]
  • Sloan Research Fellow in Chemistry, Alfred P. Sloan Foundation, 2018 – 2020[39]
  • Pfizer-Laubach Career Development Professorship, MIT, 2017 – 2020[40]
  • Associate Scientific Advisor, Science Translational Medicine, 2016[41]
  • NIH Director's New Innovator Award, 2015 – 2020[42]
  • Beckman Young Investigators Award Arnold and Mabel Beckman Foundation, 2015 – 2019[43]
  • Searle Scholars Program[44]
  • "Follow That Cell” Competition First Place (team member), NIH, 2015[45]
  • Hermann L.F. von Helmholtz Career Development Professorship, MIT, 2014 – 2016[45]
  • Excellence Award, Broad Institute of Harvard and MIT, 2013[45]
  • Dudley R. Herschbach Teaching Award, Harvard University, 2006[45]
  • Graduate Research Fellowship, NSF, 2005 – 2008[45]
  • Certificate of Distinction in Teaching, Harvard University, 2005[45]
  • Phi Beta Kappa, Columbia University, 2004[45]
  • John Jay Scholar, Columbia University, 2000 – 2004[45]

Select publications

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  • Huang, Siyi et al. (2021-01-21). "Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential". Cell. 184 (2): 441–459.e25[34]
  • Ziegler, C.G.K. et al. (2020-05-28). “SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues,” Cell, 181, 1016 (2020).[20]
  • Hughes, Travis K. et al. (2020-10-13). "Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies". Immunity. 53 (4): 878–894.e7.[8]
  • Kotliar, Dylan et al. (2020-11-25). "Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics". Cell. 183 (5): 1383–1401.e19.[10]
  • Kazer, Samuel W. et al. (2020-04). "Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection". Nature Medicine. 26 (4): 511–518.[9]
  • Smillie, C.# et al. (2019). “Intra- and inter-cellular rewiring of the human colon during ulcerative colitis” Cell, 178, 714 (2019).[29]
  • Ordovas-Montanes, J. et al. (2018). “Reduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity,” Nature, 560, 649 (2018).[28]
  • Martin-Gayo, E. et al. (2018). “A Rational Framework for Modulating Ensemble Immune Behaviors Inspired by HIV-1 Elite Control”, Genome Biol., 19, 10 (2018).[26]
  • T. M. Gierahn et al. (2017) “Seq-Well: A Portable, Low-cost Platform for Single-Cell RNA-Seq of Low-Input Samples.” Nature Meth. 14 (2017): 395.[5]
  • I. Tirosh et al. (2017) “Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.” Science 352.6282 (2016): 189-96.[15]
  • E. Z. Macosko et al. (2015). “Genome-wide expression profiling of thousands of individual cells using nanoliter droplets.” Cell 161 (2015): 1202-14.[7]
  • A. K. Shalek et al. (2014). “Large-Scale Single-Cell RNA-Seq Reveals Strategies for Regulating Cell-to-Cell Dynamic Variability through Paracrine Signaling.” Nature 510 (2014): 363.[4]
  • A. K. Shalek et al. (2013). “Single-Cell Transcriptomics Reveals Bimodality in Expression and Splicing in Immune Cells.” Nature 498 (2013): 236-40.[3]
  • N. Yosef et al. (2013). “Dynamic Regulatory Network Controlling Th17 Cell Differentiation.” Nature 496 (2013): 461-68.[46]

References

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  1. ^ "Shalek Lab". shaleklab.com. Retrieved 2020-10-30.
  2. ^ Robinson, Jacob T.; Jorgolli, Marsela; Shalek, Alex K.; Yoon, Myung-Han; Gertner, Rona S.; Park, Hongkun (March 2012). "Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits". Nature Nanotechnology. 7 (3): 180–184. Bibcode:2012NatNa...7..180R. doi:10.1038/nnano.2011.249. ISSN 1748-3395. PMC 4209482. PMID 22231664.
  3. ^ a b Shalek, Alex K.; Satija, Rahul; Adiconis, Xian; Gertner, Rona S.; Gaublomme, Jellert T.; Raychowdhury, Raktima; Schwartz, Schraga; Yosef, Nir; Malboeuf, Christine; Lu, Diana; Trombetta, John J. (June 2013). "Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells". Nature. 498 (7453): 236–240. Bibcode:2013Natur.498..236S. doi:10.1038/nature12172. ISSN 1476-4687. PMC 3683364. PMID 23685454.
  4. ^ a b Shalek, Alex K.; Satija, Rahul; Shuga, Joe; Trombetta, John J.; Gennert, Dave; Lu, Diana; Chen, Peilin; Gertner, Rona S.; Gaublomme, Jellert T.; Yosef, Nir; Schwartz, Schraga (June 2014). "Single-cell RNA-seq reveals dynamic paracrine control of cellular variation". Nature. 510 (7505): 363–369. Bibcode:2014Natur.510..363S. doi:10.1038/nature13437. ISSN 1476-4687. PMC 4193940. PMID 24919153.
  5. ^ a b c d Gierahn, Todd M.; Wadsworth, Marc H.; Hughes, Travis K.; Bryson, Bryan D.; Butler, Andrew; Satija, Rahul; Fortune, Sarah; Love, J. Christopher; Shalek, Alex K. (April 2017). "Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput". Nature Methods. 14 (4): 395–398. doi:10.1038/nmeth.4179. hdl:1721.1/113430. ISSN 1548-7105. PMC 5376227. PMID 28192419.
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  9. ^ a b c d Kazer, Samuel W.; Aicher, Toby P.; Muema, Daniel M.; Carroll, Shaina L.; Ordovas-Montanes, Jose; Miao, Vincent N.; Tu, Ang A.; Ziegler, Carly G. K.; Nyquist, Sarah K.; Wong, Emily B.; Ismail, Nasreen (April 2020). "Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection". Nature Medicine. 26 (4): 511–518. doi:10.1038/s41591-020-0799-2. ISSN 1546-170X. PMC 7237067. PMID 32251406.
  10. ^ a b c d Kotliar, Dylan; Lin, Aaron E.; Logue, James; Hughes, Travis K.; Khoury, Nadine M.; Raju, Siddharth S.; Wadsworth, Marc H.; Chen, Han; Kurtz, Jonathan R.; Dighero-Kemp, Bonnie; Bjornson, Zach B. (2020-11-25). "Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics". Cell. 183 (5): 1383–1401.e19. doi:10.1016/j.cell.2020.10.002. ISSN 0092-8674. PMC 7707107. PMID 33159858.
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  13. ^ Tu, Ang A.; Gierahn, Todd M.; Monian, Brinda; Morgan, Duncan M.; Mehta, Naveen K.; Ruiter, Bert; Shreffler, Wayne G.; Shalek, Alex K.; Love, J. Christopher (December 2019). "TCR sequencing paired with massively parallel 3′ RNA-seq reveals clonotypic T cell signatures". Nature Immunology. 20 (12): 1692–1699. doi:10.1038/s41590-019-0544-5. ISSN 1529-2916. PMC 7528220. PMID 31745340.
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  16. ^ Lohr, Jens G.; Adalsteinsson, Viktor A.; Cibulskis, Kristian; Choudhury, Atish D.; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua M.; Zhang, Cheng-Zhong; Shalek, Alex K.; Satija, Rahul; Trombetta, John J. (May 2014). "Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer". Nature Biotechnology. 32 (5): 479–484. doi:10.1038/nbt.2892. ISSN 1546-1696. PMC 4034575. PMID 24752078.
  17. ^ a b Patel, Anoop P.; Tirosh, Itay; Trombetta, John J.; Shalek, Alex K.; Gillespie, Shawn M.; Wakimoto, Hiroaki; Cahill, Daniel P.; Nahed, Brian V.; Curry, William T.; Martuza, Robert L.; Louis, David N. (2014-06-20). "Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma". Science. 344 (6190): 1396–1401. Bibcode:2014Sci...344.1396P. doi:10.1126/science.1254257. ISSN 0036-8075. PMC 4123637. PMID 24925914.
  18. ^ a b Hamza, Bashar; Ng, Sheng Rong; Prakadan, Sanjay M.; Delgado, Francisco Feijó; Chin, Christopher R.; King, Emily M.; Yang, Lucy F.; Davidson, Shawn M.; DeGouveia, Kelsey L.; Cermak, Nathan; Navia, Andrew W. (2019-02-05). "Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer". Proceedings of the National Academy of Sciences. 116 (6): 2232–2236. Bibcode:2019PNAS..116.2232H. doi:10.1073/pnas.1814102116. ISSN 0027-8424. PMC 6369805. PMID 30674677.
  19. ^ a b Kimmerling, Robert J.; Prakadan, Sanjay M.; Gupta, Alejandro J.; Calistri, Nicholas L.; Stevens, Mark M.; Olcum, Selim; Cermak, Nathan; Drake, Riley S.; Pelton, Kristine; De Smet, Frederik; Ligon, Keith L. (2018-11-27). "Linking single-cell measurements of mass, growth rate, and gene expression". Genome Biology. 19 (1): 207. doi:10.1186/s13059-018-1576-0. ISSN 1474-760X. PMC 6260722. PMID 30482222.
  20. ^ a b Ziegler, Carly G. K.; Allon, Samuel J.; Nyquist, Sarah K.; Mbano, Ian M.; Miao, Vincent N.; Tzouanas, Constantine N.; Cao, Yuming; Yousif, Ashraf S.; Bals, Julia; Hauser, Blake M.; Feldman, Jared (2020-05-28). "SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues". Cell. 181 (5): 1016–1035.e19. doi:10.1016/j.cell.2020.04.035. ISSN 0092-8674. PMC 7252096. PMID 32413319.
  21. ^ a b Gideon, Hannah P.; Hughes, Travis K.; Wadsworth, Marc H.; Tu, Ang Andy; Gierahn, Todd M.; Hopkins, Forrest F.; Wei, Jun-Rong; Kummerlowe, Conner; Grant, Nicole L.; Nargan, Kievershen; Phuah, JiaYao (2020-10-26). "Single-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte signatures of bacterial control". bioRxiv: 2020.10.24.352492. doi:10.1101/2020.10.24.352492. S2CID 226229228.
  22. ^ a b Waldman, Benjamin S.; Schwarz, Dominic; Wadsworth, Marc H.; Saeij, Jeroen P.; Shalek, Alex K.; Lourido, Sebastian (2020-01-23). "Identification of a Master Regulator of Differentiation in Toxoplasma". Cell. 180 (2): 359–372.e16. doi:10.1016/j.cell.2019.12.013. ISSN 0092-8674. PMC 6978799. PMID 31955846.
  23. ^ a b Darrah, Patricia A.; Zeppa, Joseph J.; Maiello, Pauline; Hackney, Joshua A.; Wadsworth, Marc H.; Hughes, Travis K.; Pokkali, Supriya; Swanson, Phillip A.; Grant, Nicole L.; Rodgers, Mark A.; Kamath, Megha (January 2020). "Prevention of tuberculosis in macaques after intravenous BCG immunization". Nature. 577 (7788): 95–102. Bibcode:2020Natur.577...95D. doi:10.1038/s41586-019-1817-8. ISSN 1476-4687. PMC 7015856. PMID 31894150.
  24. ^ Ranasinghe, Srinika; Lamothe, Pedro A.; Soghoian, Damien Z.; Kazer, Samuel W.; Cole, Michael B.; Shalek, Alex K.; Yosef, Nir; Jones, R. Brad; Donaghey, Faith; Nwonu, Chioma; Jani, Priya (2016-10-18). "Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion". Immunity. 45 (4): 917–930. doi:10.1016/j.immuni.2016.09.015. ISSN 1074-7613. PMC 5077698. PMID 27760342.
  25. ^ a b Raghavan, Srivatsan; Winter, Peter S.; Navia, Andrew W.; Williams, Hannah L.; DenAdel, Alan; Kalekar, Radha L.; Galvez-Reyes, Jennyfer; Lowder, Kristen E.; Mulugeta, Nolawit; Raghavan, Manisha S.; Borah, Ashir A. (2020-08-25). "Transcriptional subtype-specific microenvironmental crosstalk and tumor cell plasticity in metastatic pancreatic cancer". bioRxiv: 2020.08.25.256214. doi:10.1101/2020.08.25.256214. S2CID 221355597.
  26. ^ a b c Martin-Gayo, Enrique; Cole, Michael B.; Kolb, Kellie E.; Ouyang, Zhengyu; Cronin, Jacqueline; Kazer, Samuel W.; Ordovas-Montanes, Jose; Lichterfeld, Mathias; Walker, Bruce D.; Yosef, Nir; Shalek, Alex K. (2018-01-29). "A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers". Genome Biology. 19 (1): 10. doi:10.1186/s13059-017-1385-x. ISSN 1474-760X. PMC 5789701. PMID 29378643.
  27. ^ Kløverpris, Henrik N.; Kazer, Samuel W.; Mjösberg, Jenny; Mabuka, Jenniffer M.; Wellmann, Amanda; Ndhlovu, Zaza; Yadon, Marisa C.; Nhamoyebonde, Shepherd; Muenchhoff, Maximilian; Simoni, Yannick; Andersson, Frank (2016-02-16). "Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression". Immunity. 44 (2): 391–405. doi:10.1016/j.immuni.2016.01.006. ISSN 1074-7613. PMC 6836297. PMID 26850658.
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  30. ^ "Technique identifies T cells primed for certain allergies or infections: Researchers develop a method to isolate and sequence the RNA of T cells that react to a specific target". ScienceDaily. Retrieved 2021-02-17.
  31. ^ Majumder, Partha P.; Mhlanga, Musa M.; Shalek, Alex K. (October 2020). "The Human Cell Atlas and equity: lessons learned". Nature Medicine. 26 (10): 1509–1511. arXiv:2010.16154. doi:10.1038/s41591-020-1100-4. ISSN 1546-170X. PMID 33029017.
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  34. ^ a b Huang, Siyi; Ziegler, Carly G. K.; Austin, John; Mannoun, Najat; Vukovic, Marko; Ordovas-Montanes, Jose; Shalek, Alex K.; Andrian, Ulrich H. von (2021-01-21). "Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential". Cell. 184 (2): 441–459.e25. doi:10.1016/j.cell.2020.11.028. ISSN 0092-8674. PMC 9612289. PMID 33333021.
  35. ^ Nirschl, Christopher J.; Suárez-Fariñas, Mayte; Izar, Benjamin; Prakadan, Sanjay; Dannenfelser, Ruth; Tirosh, Itay; Liu, Yong; Zhu, Qian; Devi, K. Sanjana P.; Carroll, Shaina L.; Chau, David (2017-06-29). "IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment". Cell. 170 (1): 127–141.e15. doi:10.1016/j.cell.2017.06.016. ISSN 0092-8674. PMC 5569303. PMID 28666115.
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  46. ^ Yosef, Nir; Shalek, Alex K.; Gaublomme, Jellert T.; Jin, Hulin; Lee, Youjin; Awasthi, Amit; Wu, Chuan; Karwacz, Katarzyna; Xiao, Sheng; Jorgolli, Marsela; Gennert, David (April 2013). "Dynamic regulatory network controlling T H 17 cell differentiation". Nature. 496 (7446): 461–468. Bibcode:2013Natur.496..461Y. doi:10.1038/nature11981. ISSN 1476-4687. PMC 3637864. PMID 23467089.
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