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Alex Kentsis (born Oleg Emilievich Kentsis, 1975) is a Jewish-American scientist and physician, and Professor of Pediatrics, Pharmacology, Physiology & Biophysics at the Memorial Sloan Kettering Cancer Center; and Associate Professor at Weill Medical College of Cornell University, known for his contributions to understanding biological self-organization, protein folding, cell signaling, and cancer therapeutics.[1][2][3]

Education and Career

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Kentsis received his Bachelor's degree (AB) in Biological Sciences and Master's degree (SM) in Biochemistry from the University of Chicago. He went on to earn his Doctor of Medicine (MD) and Doctor of Philosophy (PhD) in Biophysics from the Mount Sinai School of Medicine of New York University (now Icahn School of Medicine at Mount Sinai). He completed his clinical training in pediatrics at the Boston Children's Hospital and pediatric hematology-oncology at the Dana-Farber Cancer Institute at the Harvard Medical School.

In 2013, he joined the faculty of the Memorial Sloan Kettering Cancer Center as an assistant member and assistant professor, where he is currently Member and Professor of Pediatrics, Pharmacology, Physiology & Biophysics, and founding Director of the Tow Center for Developmental Oncology.[4]

Research

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As a student with Tobin Sosnick, Kentsis contributed to understanding protein folding, including effects of hydration now used in molecular design.[5] As a student with Katherine Borden, Kentsis used protein engineering approaches to investigate cellular scaffolds and defined a distinct mechanism of protein self-assembly relevant to various physiological processes.[6][7][8] His work on the promyelocytic leukemia (PML) nuclear body supported the development of ribavirin for cancer therapy.[9][10]

Kentsis has advocated for the use of biological mass spectrometry and proteomics for the discovery of disease biomarkers and therapeutic targets.[11][12][13][14][15] His work with Thomas Look investigated the mechanisms of autocrine receptor tyrosine kinase signaling in acute myeloid leukemias,[16] contributing to the general mechanism of adaptive cancer therapy resistance by feedback activation, alongside similar studies by Neal Rosen, Todd Golub, and Jeff Engelman, leading to clinical trials for patients.[17][18] Subsequently, his laboratory has elucidated genetic and epigenetic mechanisms of chemotherapy resistance and therapies targeting oncogenic transcription factors.[19][20][21][22]

Since 2015, Kentsis' research in childhood cancer biology identified developmental mechanisms of site-specific oncogenic mutations.[23][24][25] This established the concept of developmental mutators, proposing a unified theory of why specific cancers develop in young people.[26][27]

As of 2024, Kentsis has authored over 120 publications, with over 8000 citations.[28]

Awards and Honors

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  • Burroughs Wellcome Fund Career Award for Medical Scientists (2013)[29]
  • Scholar Award, American Society of Hematology (2014)[30]
  • Scholar Award, Rita Allen Foundation (2016)[31]
  • Clinical Investigator Award, Damon Runyon Cancer Research Foundation (2016)[32]
  • St. Baldrick's Foundation Robert J. Arceci Innovation Award (2018)[33]
  • Young Investigator Award, Society for Pediatric Research (2018)[34]
  • Elected Member, American Society for Clinical Investigation (2018)[35]
  • Scholar Award, Leukemia and Lymphoma Society (2019)[36]
  • Pershing Square Sohn Prize (2019)[37]
  • Boyer Clinical Research Award (2020)[38]

Personal Life

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Kentsis was born in 1975 in Kishinev, Moldavian SSR (now Chișinău, Moldova) when it was part of the Soviet Union. Escaping antisemitism, his family emigrated to USA in 1989. He is married to Nina Kentsis (née Shapiro), a researcher and writer,[39] and they have two children.

References

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  1. ^ "Kentsis Lab". Retrieved October 15, 2024.
  2. ^ "Alex Kentsis, MD, PhD at the Memorial Sloan Kettering Cancer Center". Retrieved October 15, 2024.
  3. ^ "Alex Kentsis | Graduate School of Medical Sciences". gradschool.weill.cornell.edu. Retrieved 2024-10-31.
  4. ^ "Tow Center for Developmental Oncology". 5 February 2024. Retrieved October 15, 2024.
  5. ^ Kentsis, Alex; Sosnick, Tobin R. (1998-10-01). "Trifluoroethanol Promotes Helix Formation by Destabilizing Backbone Exposure: Desolvation Rather than Native Hydrogen Bonding Defines the Kinetic Pathway of Dimeric Coiled Coil Folding". Biochemistry. 37 (41): 14613–14622. doi:10.1021/bi981641y. ISSN 0006-2960. PMID 9772190.
  6. ^ Kentsis A, Gordon RE, Borden KL. "Control of biochemical reactions through supramolecular RING domain self-assembly". Roceedings of the National Academy of Science U S A. 99 (24): 15404–9. doi:10.1073/pnas.252510999 (inactive 2024-10-16).{{cite journal}}: CS1 maint: DOI inactive as of October 2024 (link) CS1 maint: multiple names: authors list (link)
  7. ^ Kentsis A, Gordon RE, Borden KL (2002). "Self-assembly properties of a model RING domain". Proceedings of the National Academy of Science U S A. 99 (2): 667–72. doi:10.1073/pnas.012317299. PMC 117363. PMID 11792829.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ "Organization RINGleader". Science. 298 (5601): 2095. 2002-12-13. doi:10.1126/science.298.5601.2095b. ISSN 0036-8075.
  9. ^ Kentsis A, Topisirovic I, Culjkovic B, Shao L, Borden KL (2004). "Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap". Proceedings of the National Academy of Science U S A. 101 (52): 18105–10. Bibcode:2004PNAS..10118105K. doi:10.1073/pnas.0406927102. PMC 539790. PMID 15601771.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Borden KLB, Culjkovic-Kraljacic B (2010). "Ribavirin as an anti-cancer therapy: acute myeloid leukemia and beyond?". Leuk Lymphoma. 51 (10): 1805–1815. doi:10.3109/10428194.2010.496506. ISSN 1042-8194. PMC 2950216. PMID 20629523.
  11. ^ Kentsis, Alex; Monigatti, Flavio; Dorff, Kevin; Campagne, Fabien; Bachur, Richard; Steen, Hanno (2009-09-01). "Urine proteomics for profiling of human disease using high accuracy mass spectrometry". Proteomics. Clinical Applications. 3 (9): 1052–1061. doi:10.1002/prca.200900008. ISSN 1862-8346. PMC 2994589. PMID 21127740.
  12. ^ Cifani, Paolo; Kentsis, Alex (2017). "High Sensitivity Quantitative Proteomics Using Automated Multidimensional Nano-flow Chromatography and Accumulated Ion Monitoring on Quadrupole-Orbitrap-Linear Ion Trap Mass Spectrometer". Molecular & Cellular Proteomics : MCP. 16 (11): 2006–2016. doi:10.1074/mcp.RA117.000023. ISSN 1535-9476. PMC 5672005. PMID 28821601.
  13. ^ Cifani, Paolo; Dhabaria, Avantika; Chen, Zining; Yoshimi, Akihide; Kawaler, Emily; Abdel-Wahab, Omar; Poirier, John T.; Kentsis, Alex (2018-11-02). "ProteomeGenerator: A Framework for Comprehensive Proteomics Based on de Novo Transcriptome Assembly and High-Accuracy Peptide Mass Spectral Matching". Journal of Proteome Research. 17 (11): 3681–3692. doi:10.1021/acs.jproteome.8b00295. ISSN 1535-3893. PMC 6727203. PMID 30295032.
  14. ^ Cifani P, Kentsis A (2022). "Quantitative Cell Proteomic Atlas: Pathway-Scale Targeted Mass Spectrometry for High-Resolution Functional Profiling of Cell Signaling". J Proteome Res. 21 (10): 2535–2544. doi:10.1021/acs.jproteome.2c00223. PMC 10494574. PMID 36154077.
  15. ^ "Analyzing Urine Can Guide the Treatment of Childhood Kidney Tumors". 8 August 2019. Retrieved October 15, 2024.
  16. ^ Kentsis, Alex; Reed, Casie; Rice, Kim L.; Sanda, Takaomi; Rodig, Scott J.; Tholouli, Eleni; Christie, Amanda; Valk, Peter J.M.; Delwel, Ruud; Ngo, Vu; Kutok, Jeffery L.; Dahlberg, Suzanne E.; Moreau, Lisa A.; Byers, Richard J.; Christensen, James G. (2012). "Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia". Nature Medicine. 18 (7): 1118–1122. doi:10.1038/nm.2819. ISSN 1078-8956. PMC 3438345. PMID 22683780.
  17. ^ Chen, Evan C.; Gandler, Helen; Tošić, Isidora; Fell, Geoffrey G.; Fiore, Ashlee; Pozdnyakova, Olga; DeAngelo, Daniel J.; Galinsky, Ilene; Luskin, Marlise R.; Wadleigh, Martha; Winer, Eric S.; Leonard, Rebecca; O'Day, Kelsey; de Jonge, Adrienne; Neuberg, Donna (2023-03-01). "Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates". Clinical Cancer Research. 29 (5): 878–887. doi:10.1158/1078-0432.CCR-22-2540. ISSN 1078-0432. PMC 9992000. PMID 36534523.
  18. ^ Wang, Victoria E.; Blaser, Bradley W.; Patel, Ravi K.; Behbehani, Gregory K.; Rao, Arjun A.; Durbin-Johnson, Blythe; Jiang, Tommy; Logan, Aaron C.; Settles, Matthew; Mannis, Gabriel N.; Olin, Rebecca; Damon, Lloyd E.; Martin, Thomas G.; Sayre, Peter H.; Gaensler, Karin M. (2021-09-01). "Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis". Blood Cancer Discovery. 2 (5): 434–449. doi:10.1158/2643-3230.BCD-21-0055. ISSN 2643-3230. PMC 8425277. PMID 34514432.
  19. ^ Brown, Fiona C.; Still, Eric; Koche, Richard P.; Yim, Christina Y.; Takao, Sumiko; Cifani, Paolo; Reed, Casie; Gunasekera, Shehana; Ficarro, Scott B.; Romanienko, Peter; Mark, Willie; McCarthy, Craig; de Stanchina, Elisa; Gonen, Mithat; Seshan, Venkatraman (2018). "MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia". Cancer Discovery. 8 (4): 478–497. doi:10.1158/2159-8290.CD-17-1271. ISSN 2159-8274. PMC 5882571. PMID 29431698.
  20. ^ Ramaswamy, Kavitha; Forbes, Lauren; Minuesa, Gerard; Gindin, Tatyana; Brown, Fiona; Kharas, Michael G.; Krivtsov, Andrei V.; Armstrong, Scott A.; Still, Eric; de Stanchina, Elisa; Knoechel, Birgit; Koche, Richard; Kentsis, Alex (2018-01-09). "Peptidomimetic blockade of MYB in acute myeloid leukemia". Nature Communications. 9 (1): 110. Bibcode:2018NatCo...9..110R. doi:10.1038/s41467-017-02618-6. ISSN 2041-1723. PMC 5760651. PMID 29317678.
  21. ^ Grisham, Julie (February 18, 2019). "Research Uncovers the Genetic Causes of Aggressive Leukemia in Children". MSK News. Retrieved October 15, 2024.
  22. ^ Stallard, Jim (February 5, 2021). "Research Shows How Common Feature of Blood Cancers Can Be Targeted". MSK News. Retrieved October 15, 2024.
  23. ^ Henssen, Anton G.; Koche, Richard; Zhuang, Jiali; Jiang, Eileen; Reed, Casie; Eisenberg, Amy; Still, Eric; MacArthur, Ian C.; Rodríguez-Fos, Elias; Gonzalez, Santiago; Puiggròs, Montserrat; Blackford, Andrew N.; Mason, Christopher E.; de Stanchina, Elisa; Gönen, Mithat (2017). "PGBD5 promotes site-specific oncogenic mutations in human tumors". Nature Genetics. 49 (7): 1005–1014. doi:10.1038/ng.3866. ISSN 1061-4036. PMC 5489359. PMID 28504702.
  24. ^ Henssen, Anton G.; Reed, Casie; Jiang, Eileen; Garcia, Heathcliff Dorado; von Stebut, Jennifer; MacArthur, Ian C.; Hundsdoerfer, Patrick; Kim, Jun Hyun; de Stanchina, Elisa; Kuwahara, Yasumichi; Hosoi, Hajime; Ganem, Neil; Cruz, Filemon Dela; Kung, Andrew L.; Schulte, Johannes H. (2017-11-01). "Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors". Science Translational Medicine. 9 (414): eaam9078. doi:10.1126/scitranslmed.aam9078. ISSN 1946-6234. PMC 5683417. PMID 29093183.
  25. ^ Yamada, Makiko; Keller, Ross R.; Gutierrez, Rodrigo Lopez; Cameron, Daniel; Suzuki, Hiromichi; Sanghrajka, Reeti; Vaynshteyn, Jake; Gerwin, Jeffrey; Maura, Francesco; Hooper, William; Shah, Minita; Robine, Nicolas; Demarest, Phillip; Bayin, N. Sumru; Zapater, Luz Jubierre (2024-03-22). "Childhood cancer mutagenesis caused by transposase-derived PGBD5". Science Advances. 10 (12): eadn4649. Bibcode:2024SciA...10N4649Y. doi:10.1126/sciadv.adn4649. ISSN 2375-2548. PMC 10959420. PMID 38517960.
  26. ^ Kentsis, Alex (2020). "Why do young people get cancer?". Pediatric Blood & Cancer. 67 (7): e28335. doi:10.1002/pbc.28335. ISSN 1545-5009. PMC 7582786. PMID 32391946.
  27. ^ Kentsis, Alex (2024). "Toward a Unified Theory of Why Young People Develop Cancer". Cold Spring Harbor Perspectives in Medicine. 14 (10): a041658. doi:10.1101/cshperspect.a041658. ISSN 2157-1422. PMC 11444251. PMID 38692742.
  28. ^ "Alex Kentsis - Google Scholar". Retrieved October 15, 2024.
  29. ^ "Alex Kentsis - BWF Career Award".
  30. ^ "Alex Kentsis - ASH Scholar Award". Retrieved October 14, 2024.
  31. ^ "Alex Kentsis - Rita Allen Foundation". Retrieved October 14, 2024.
  32. ^ "Alex Kentsis - Damon Runyon Cancer Research Foundation". Retrieved October 14, 2024.
  33. ^ "PRNewswire: St. Baldrick's Foundation Supports Innovative Childhood Cancer Research Through One-of-a-Kind Grant" (Press release). Retrieved October 14, 2024.
  34. ^ "Alex Kentsis - Society for Pediatric Research Award". Retrieved October 14, 2024.
  35. ^ "Alex Kentsis, American Society for Clinical Investigation". Retrieved October 14, 2024.
  36. ^ "Alex Kentsis - Leukemia & Lymphoma Society Scholar". Retrieved October 14, 2024.
  37. ^ "Alex Kentsis - Pershing Square Sohn Prize". Retrieved October 14, 2024.
  38. ^ "Alex Kentsis - Boyer Award".
  39. ^ "Nina Kentsis". Retrieved October 14, 2024.
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