Alex K. Shalek Explained

Alex Shalek
Birth Date:December 18, 1981
Work Institutions:Massachusetts Institute of Technology
Broad Institute
Koch Institute for Integrative Cancer Research
Ragon Institute
Mass General Hospital
Harvard Medical School
Awards: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)
Alma Mater:Columbia University
Harvard University
Doctoral Advisor:Hongkun Park

Alex K. Shalek is a biomedical engineer, and a core faculty member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. Additionally, he is a Member of the Ragon Institute and 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

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. In parallel, they have used these and other approaches [7] [8] [9] [10] [11] to help examine the causes and consequences of cellular heterogeneity across cancers,[12] [13] [14] [15] [16] infectious diseases,[17] [18] [19] [20] [21] [22] [23] and inflammation.[24] [25]

Ongoing research

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,[26] the lab is applying them to dissect human diseases, like COVID-19,[27] [28] methodically linking cellular features and clinical observations. Major areas of focus include how: immune cells coordinate balanced responses to environmental stresses; host cell-pathogen interactions evolve during infection; and, tumor cells evade therapeutic treatment and natural immunity.[29]

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

Select publications

References

  1. Web site: Shalek Lab. 2020-10-30. shaleklab.com.
  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. en. 7. 3. 180–184. 10.1038/nnano.2011.249. 22231664. 1748-3395. 4209482. 2012NatNa...7..180R.
  3. 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. en. 498. 7453. 236–240. 10.1038/nature12172. 23685454. 1476-4687. 3683364. 2013Natur.498..236S.
  4. 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. en. 510. 7505. 363–369. 10.1038/nature13437. 24919153. 1476-4687. 4193940. 2014Natur.510..363S.
  5. 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. en. 14. 4. 395–398. 10.1038/nmeth.4179. 28192419. 5376227. 1548-7105. 1721.1/113430. free.
  6. Web site: Making single-cell RNA sequencing widely available. 2021-02-17. MIT News Massachusetts Institute of Technology. 13 February 2017 . en.
  7. 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. en. 26. 4. 511–518. 10.1038/s41591-020-0799-2. 32251406. 7237067. 1546-170X. free.
  8. Genshaft. Alex S.. Li. Shuqiang. Gallant. Caroline J.. Darmanis. Spyros. Prakadan. Sanjay M.. Ziegler. Carly G. K.. Lundberg. Martin. Fredriksson. Simon. Hong. Joyce. Regev. Aviv. Livak. Kenneth J.. 2016-09-19. Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction. Genome Biology. 17. 1. 188. 10.1186/s13059-016-1045-6. 1474-760X. 5027636. 27640647 . free .
  9. Kimmerling. Robert J.. Lee Szeto. Gregory. Li. Jennifer W.. Genshaft. Alex S.. Kazer. Samuel W.. Payer. Kristofor R.. de Riba Borrajo. Jacob. Blainey. Paul C.. Irvine. Darrell J.. Shalek. Alex K.. Manalis. Scott R.. 2016-01-06. A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages. Nature Communications. en. 7. 1. 10220. 10.1038/ncomms10220. 26732280. 4729820. 2016NatCo...710220K. 2041-1723. free.
  10. 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. en. 20. 12. 1692–1699. 10.1038/s41590-019-0544-5. 31745340. 7528220. 1529-2916. free.
  11. Galen. Peter van. Hovestadt. Volker. Ii. Marc H. Wadsworth. Hughes. Travis K.. Griffin. Gabriel K.. Battaglia. Sofia. Verga. Julia A.. Stephansky. Jason. Pastika. Timothy J.. Story. Jennifer Lombardi. Pinkus. Geraldine S.. Geraldine Pinkus. 2019-03-07. Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity. Cell. English. 176. 6. 1265–1281.e24. 10.1016/j.cell.2019.01.031. 0092-8674. 30827681. 6515904. free.
  12. Tirosh. Itay. Izar. Benjamin. Prakadan. Sanjay M.. Wadsworth. Marc H.. Treacy. Daniel. Trombetta. John J.. Rotem. Asaf. Rodman. Christopher. Lian. Christine. Murphy. George. Fallahi-Sichani. Mohammad. 2016-04-08. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. en. 352. 6282. 189–196. 10.1126/science.aad0501. 0036-8075. 27124452. 4944528. 2016Sci...352..189T. free.
  13. 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. en. 32. 5. 479–484. 10.1038/nbt.2892. 24752078. 1546-1696. 4034575.
  14. 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. en. 344. 6190. 1396–1401. 10.1126/science.1254257. 0036-8075. 24925914. 4123637. 2014Sci...344.1396P.
  15. 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. en. 116. 6. 2232–2236. 10.1073/pnas.1814102116. 0027-8424. 30674677. 6369805. 2019PNAS..116.2232H . free.
  16. 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. 10.1186/s13059-018-1576-0. 1474-760X. 6260722. 30482222 . free .
  17. 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. English. 181. 5. 1016–1035.e19. 10.1016/j.cell.2020.04.035. 0092-8674. 32413319. 7252096. free.
  18. 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. en. 2020.10.24.352492. 10.1101/2020.10.24.352492. 226229228.
  19. 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. English. 180. 2. 359–372.e16. 10.1016/j.cell.2019.12.013. 0092-8674. 31955846. 6978799. free.
  20. 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. en. 577. 7788. 95–102. 10.1038/s41586-019-1817-8. 31894150. 7015856. 2020Natur.577...95D. 1476-4687. free.
  21. 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. English. 45. 4. 917–930. 10.1016/j.immuni.2016.09.015. 1074-7613. 27760342. 5077698. free.
  22. 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. en. 2020.08.25.256214. 10.1101/2020.08.25.256214. 221355597.
  23. 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. English. 44. 2. 391–405. 10.1016/j.immuni.2016.01.006. 1074-7613. 26850658. 6836297. free.
  24. Ordovas-Montanes. Jose. Dwyer. Daniel F.. Nyquist. Sarah K.. Buchheit. Kathleen M.. Vukovic. Marko. Deb. Chaarushena. Wadsworth. Marc H.. Hughes. Travis K.. Kazer. Samuel W.. Yoshimoto. Eri. Cahill. Katherine N.. August 2018. Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature. en. 560. 7720. 649–654. 10.1038/s41586-018-0449-8. 30135581. 6133715. 2018Natur.560..649O. 1476-4687. 1721.1/122932. free.
  25. Web site: 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. 2021-02-17. ScienceDaily. en.
  26. Majumder. Partha P.. Mhlanga. Musa M.. Shalek. Alex K.. October 2020. The Human Cell Atlas and equity: lessons learned. Nature Medicine. en. 26. 10. 1509–1511. 10.1038/s41591-020-1100-4. 2010.16154 . 33029017. 1546-170X. free.
  27. Web site: Researchers identify cells likely targeted by Covid-19 virus. 2021-02-17. MIT News Massachusetts Institute of Technology. 22 April 2020 . en.
  28. Web site: Into the Lungs and Beyond. 2021-02-17. hms.harvard.edu. 29 April 2020 . en.
  29. 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. English. 170. 1. 127–141.e15. 10.1016/j.cell.2017.06.016. 0092-8674. 28666115. 5569303. free.
  30. Web site: Alex Shalek wins Edgerton Faculty Award. 2020-12-11. MIT News Massachusetts Institute of Technology. 23 April 2020 . en.
  31. Web site: Excellence in Mentoring Awards. 2020-12-11. The Office for Diversity Inclusion and Community Partnership at Harvard Medical School.
  32. Web site: Shalek named 2018 Pew-Stewart Scholar for Cancer Research – MIT Department of Chemistry. 14 June 2018 . 2020-12-11. en-US.
  33. Web site: 2018-02-15. IMES Professor Alex Shalek wins 2018 Sloan Research Fellowship. 2021-02-09. Institute for Medical Engineering & Science. en-US.
  34. Web site: Alex Shalek named Pfizer-Laubach Career Development Professor – Shalek Lab. 2020-12-11. shaleklab.com. 2 July 2017 .
  35. Web site: Previous ASAs Science Translational Medicine. 2021-02-17. stm.sciencemag.org.
  36. Web site: 2015-10-06. Shalek Awarded NIH New Innovator Award. 2020-12-11. Ragon Institute of MGH, MIT and Harvard. en-US.
  37. Web site: Alex Shalek. 2020-12-11. Arnold and Mabel Beckman Foundation. en-US.
  38. Web site: Searle Scholars Program . Scholar Profile Alex Shalek . 2 June 2023 . http://www.searlescholars.net/person/641 . September 5, 2015.
  39. Web site: Alex K. Shalek. 2021-02-09. Institute for Medical Engineering & Science. en-US.
  40. 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. English. 184. 2. 441–459.e25. 10.1016/j.cell.2020.11.028. 0092-8674. 33333021. 9612289 . free.
  41. Hughes. Travis K.. Wadsworth. Marc H.. Gierahn. Todd M.. Do. Tran. Weiss. David. Andrade. Priscila R.. Ma. Feiyang. Silva. Bruno J. de Andrade. Shao. Shuai. Tsoi. Lam C.. Ordovas-Montanes. Jose. 2020-10-13. Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies. Immunity. English. 53. 4. 878–894.e7. 10.1016/j.immuni.2020.09.015. 1074-7613. 33053333. 7562821. free.
  42. 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. English. 183. 5. 1383–1401.e19. 10.1016/j.cell.2020.10.002. 0092-8674. 33159858. 7707107. free.
  43. Smillie. Christopher S.. Biton. Moshe. Ordovas-Montanes. Jose. Sullivan. Keri M.. Burgin. Grace. Graham. Daniel B.. Herbst. Rebecca H.. Rogel. Noga. Slyper. Michal. Waldman. Julia. Sud. Malika. 2019-07-25. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell. English. 178. 3. 714–730.e22. 10.1016/j.cell.2019.06.029. 0092-8674. 31348891. 6662628. free.
  44. 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. 10.1186/s13059-017-1385-x. 1474-760X. 5789701. 29378643 . free .
  45. Macosko. Evan Z.. Basu. Anindita. Satija. Rahul. Nemesh. James. Shekhar. Karthik. Goldman. Melissa. Tirosh. Itay. Bialas. Allison R.. Kamitaki. Nolan. Martersteck. Emily M.. Trombetta. John J.. 2015-05-21. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell. 161. 5. 1202–1214. 10.1016/j.cell.2015.05.002. 0092-8674. 4481139. 26000488.
  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. en. 496. 7446. 461–468. 10.1038/nature11981. 23467089. 1476-4687. 3637864. 2013Natur.496..461Y.

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