Alex Kentsis

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Alex Kentsis (born Oleg Emilievich Kentsis, 1975) is a Jewish-American scientist and physician at the Memorial Sloan Kettering Cancer Center and 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]

Contents

Personal life

Kentsis was born in 1975 in Chișinău, in the Moldavian SSR of the Soviet Union (now Moldova). Escaping antisemitism, his family emigrated to USA in 1989. He is married to Nina Kentsis (née Shapiro), a researcher and writer, [4] and they have two children.

Education and career

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, where he is currently Member of the Sloan Kettering Institute and Professor of Pediatrics, Pharmacology, and Physiology & Biophysics, and founding Director of the Tow Center for Developmental Oncology. [5]

Research

As a student with Tobin Sosnick, Kentsis contributed to understanding protein folding, including effects of hydration now used in molecular design. [6] 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. [7] [8] [9] His work on the promyelocytic leukemia (PML) nuclear body supported the development of ribavirin for cancer therapy. [10] [11]

Kentsis has advocated for the use of biological mass spectrometry and proteomics for the discovery of disease biomarkers and therapeutic targets. [12] [13] [14] [15] [16] His work with Thomas Look investigated the mechanisms of autocrine receptor tyrosine kinase signaling in acute myeloid leukemias, [17] 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. [18] [19] Subsequently, his laboratory has elucidated genetic and epigenetic mechanisms of chemotherapy resistance and therapies targeting oncogenic transcription factors. [20] [21] [22] [23]

Since 2015, Kentsis' research in childhood cancer biology identified developmental mechanisms of site-specific oncogenic mutations. [24] [25] [26] This established the concept of developmental mutators, proposing a unified theory of why specific cancers develop in young people. [27] [28]

His co-edited book Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults outlines the central concept of developmental oncology, including mechanisms of genetic predisposition to young-onset cancers, their endogenous and exogenous somatic mutational processes, developmental and epigenetic regulation, immune and tissue microenvironmental control, and the development of rational and precise therapies targeting this distinct biology. [29]    

As of 2024, Kentsis has authored over 120 publications, with over 8000 citations. [30]

Awards and Honors

References

  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. ↑ "Nina Kentsis" . Retrieved October 14, 2024.
  5. ↑ "Tow Center for Developmental Oncology". 5 February 2024. Retrieved October 15, 2024.
  6. ↑ 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.
  7. ↑ Kentsis A, Gordon RE, Borden KL (2002). "Control of biochemical reactions through supramolecular RING domain self-assembly". Proceedings of the National Academy of Sciences. 99 (24): 15404–9. Bibcode:2002PNAS...9915404K. doi: 10.1073/pnas.202608799 . PMC   137729 . PMID   12438698.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Kentsis A, Gordon RE, Borden KL (2002). "Self-assembly properties of a model RING domain". Proceedings of the National Academy of Sciences. 99 (2): 667–72. doi: 10.1073/pnas.012317299 . PMC   117363 . PMID   11792829.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ↑ "Organization RINGleader". Science. 298 (5601): 2095. 2002-12-13. doi:10.1126/science.298.5601.2095b. ISSN   0036-8075.
  10. ↑ 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 Sciences. 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)
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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. 16 (11): 2006–2016. doi: 10.1074/mcp.RA117.000023 . ISSN   1535-9476. PMC   5672005 . PMID   28821601.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ "Analyzing Urine Can Guide the Treatment of Childhood Kidney Tumors". 8 August 2019. Retrieved October 15, 2024.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ Grisham, Julie (February 18, 2019). "Research Uncovers the Genetic Causes of Aggressive Leukemia in Children". MSK News. Retrieved October 15, 2024.
  23. ↑ Stallard, Jim (February 5, 2021). "Research Shows How Common Feature of Blood Cancers Can Be Targeted". MSK News. Retrieved October 15, 2024.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ Alejandro Gutierrez & Alex Kentsis (2025). Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults. Cold Spring Harbor Laboratory Press. ISBN   978-1-621825-05-0.
  30. ↑ "Alex Kentsis - Google Scholar" . Retrieved October 15, 2024.
  31. ↑ "Alex Kentsis - BWF Career Award".
  32. ↑ "Alex Kentsis - ASH Scholar Award" . Retrieved October 14, 2024.
  33. ↑ "Alex Kentsis - Rita Allen Foundation" . Retrieved October 14, 2024.
  34. ↑ "Alex Kentsis - Damon Runyon Cancer Research Foundation" . Retrieved October 14, 2024.
  35. ↑ "PRNewswire: St. Baldrick's Foundation Supports Innovative Childhood Cancer Research Through One-of-a-Kind Grant" (Press release). Retrieved October 14, 2024.
  36. ↑ "Alex Kentsis - Society for Pediatric Research Award" . Retrieved October 14, 2024.
  37. ↑ "Alex Kentsis, American Society for Clinical Investigation" . Retrieved October 14, 2024.
  38. ↑ "Alex Kentsis - Leukemia & Lymphoma Society Scholar" . Retrieved October 14, 2024.
  39. ↑ "Alex Kentsis - Pershing Square Sohn Prize" . Retrieved October 14, 2024.
  40. ↑ "Alex Kentsis - Boyer Award". 29 May 2020.
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