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Alexei Kharitonenkov

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Alexei Kharitonenkov (Russian: Алексей Игоревич Харитоненков) is a Russian-American researcher best known for his discoveries of endocrine functions of Fibroblast Growth Factor 21 (FGF21) and its prospects in developing novel therapies for metabolic diseases.[1][2][3] He is also known for his landmark identification of the signal-regulatory family of proteins (SIRPs),[4] and their corresponding protein-tyrosine phosphatases,[5] which helped unveil the molecular machinery of immune self-recognition (“do-not-eat me” signal) and their potential for the development of drugs to fight cancer.[6][7][8][9][10]

Education

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In 1985, Kharitonenkov graduated with an MS in Physics from Moscow State University (MSU), Moscow, Russia.[11] In 1990, he received a Ph.D. degree in biochemistry from MSU,[12] followed by post-doctoral fellowship trainings in molecular biology and signal transduction at the Max Planck Institute of Biochemistry (1992-1994).[13]

Career

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From 1986 to 1992, Kharitonenkov was a research fellow at Biochemistry Department, Biology Faculty, Moscow State University, Moscow, Russia.[11][12][14] Between 1994 and 1998 he was a staff scientist at the Molecular Biology department of the Max Planck Institute of Biochemistry.[4][13][15][16][17] Next, he joined Eli Lilly and Company and worked there until 2014.[18] He then moved to Calibrium, LLC.[19] Upon acquisition of this company,[20] he pursued his research at Novo Nordisk USA in 2016.[21][22] More recently, Kharitonenkov has been an executive and/or founder of startups within the biopharmaceutical field,[23][24] where he has also been an inventor.[25]

He has authored more than 100 peer-reviewed papers, most of them studying aspects of signal transduction, molecular biology, pharmacology, drug discovery and development in the areas of cancer and metabolic diseases.[26] He is also a contributing author to chapters of review books on endocrine FGFs and metabolism[27] and FGF21 as a therapeutic agent.[28] In 1997 and 2005, he contributed to priming articles describing the structures and functions of SIRPs[4] and FGF21.[29] He is named as an inventor on multiple patents.[30]

Works

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Kharitonenkov's research papers have been cited over 14,500 times.[31]

According to Google Scholar,[26] his most cited papers are:

Significance

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The discovery of FGF21's metabolic action by Kharitonenkov el. al. in 2005,[29] and 2012,[32] represents an important breakthrough in the search for pharmacological alternatives to current treatments of diabetes and other metabolic diseases,[33] as acknowledged in prominent subject reviews[1][2][3][34][35][36] and reference books.[37] Kharitonenkov’s and others' research on FGF21 mostly advocates for an adipocentric mode of action;[38][39][40][41] however, recent reports are suggestive of the brain being a primary target where this hormone would first produce its effects.[42][43] This poses some uncertainty on peripheral vs. centrallly-driven mechanism of acton of this novel metabolic regulator.

References

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  1. ^ a b Eisenstein, Michael (2005-06-01). "Growth factor discovery promises advance in diabetes research". Lab Animal. 34 (6): 10. doi:10.1038/laban0605-10b. ISSN 0093-7355. PMID 15924117. S2CID 31988407.
  2. ^ a b Seaborg, Eric (2013-04-01). "Metabolic Breakthrough". Endocrine News. Retrieved 2022-11-13.
  3. ^ a b She, Qin-Ying; Li, Li-Juan; Liu, Ming-Hong; Tan, Ru-Yu; Zhong, Yi-Wen; Bao, Jing-Fu; Xie, Jie-Dong (2022). "Bibliometric analysis of fibroblast growth factor 21 research over the period 2000 to 2021". Frontiers in Pharmacology. 13: 1011008. doi:10.3389/fphar.2022.1011008. ISSN 1663-9812. PMC 9551462. PMID 36238554.
  4. ^ a b c Kharitonenkov, A.; Chen, Z.; Sures, I.; Wang, H.; Schilling, J.; Ullrich, A. (1997-03-13). "A family of proteins that inhibit signalling through tyrosine kinase receptors". Nature. 386 (6621): 181–186. Bibcode:1997Natur.386..181K. doi:10.1038/386181a0. ISSN 0028-0836. PMID 9062191. S2CID 4259314.
  5. ^ "Google Scholar". scholar.google.es. Retrieved 2022-11-13.
  6. ^ Cambier, J. C. (1997-06-10). "Inhibitory receptors abound?". Proceedings of the National Academy of Sciences of the United States of America. 94 (12): 5993–5995. Bibcode:1997PNAS...94.5993C. doi:10.1073/pnas.94.12.5993. ISSN 0027-8424. PMC 33673. PMID 9177155.
  7. ^ Lai, Lisa A.; Zhao, Chunmei; Zhang, Eric E.; Feng, Gen-Sheng (2004), Ariño, Joaquí n; Alexander, Denis R. (eds.), "The Shp-2 tyrosine phosphatase", Protein Phosphatases, vol. 5, Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 275–299, doi:10.1007/978-3-540-40035-6_14, ISBN 978-3-540-20560-9, retrieved 2022-11-13
  8. ^ Hendriks, Wiljan J. A. J.; Böhmer, Frank-D (2016), Neel, Benjamin G.; Tonks, Nicholas K. (eds.), "Non-transmembrane PTPs in Cancer", Protein Tyrosine Phosphatases in Cancer, New York, NY: Springer New York, pp. 47–113, doi:10.1007/978-1-4939-3649-6_3, ISBN 978-1-4939-3647-2, retrieved 2022-11-13
  9. ^ Bence, Kendra K. (2016), Neel, Benjamin G.; Tonks, Nicholas K. (eds.), "Protein-Tyrosine Phosphatases: Linking Metabolism and Cancer", Protein Tyrosine Phosphatases in Cancer, New York, NY: Springer New York, pp. 307–333, doi:10.1007/978-1-4939-3649-6_12, ISBN 978-1-4939-3647-2, retrieved 2022-11-13
  10. ^ Leo, Manuela; Sabatino, Lina (2022-10-18). "Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy". International Journal of Molecular Sciences. 23 (20): 12499. doi:10.3390/ijms232012499. ISSN 1422-0067. PMC 9604048. PMID 36293358.
  11. ^ a b Kharitonenkov, A. I.; Kudriavtseva, N. G.; Bulargina, T. V. (1989-10-01). "[Preparation of monoclonal antibodies to phosphotyrosine and their use for identification of phosphotyrosine-containing proteins]". Biokhimiia (Moscow, Russia). 54 (10): 1732–1739. ISSN 0320-9725. PMID 2481508.
  12. ^ a b Kharitonenkov, A. I.; Bulargina, T. V. (1991-02-01). "[Autophosphorylation of EGF receptors in the A431 cell line with an increased intracellular concentration of Ca(2+) ions]". Biokhimiia (Moscow, Russia). 56 (2): 374–382. ISSN 0320-9725. PMID 1873350.
  13. ^ a b Møller, N. P.; Møller, K. B.; Lammers, R.; Kharitonenkov, A.; Sures, I.; Ullrich, A. (1994-08-02). "Src kinase associates with a member of a distinct subfamily of protein-tyrosine phosphatases containing an ezrin-like domain". Proceedings of the National Academy of Sciences of the United States of America. 91 (16): 7477–7481. Bibcode:1994PNAS...91.7477M. doi:10.1073/pnas.91.16.7477. ISSN 0027-8424. PMC 44424. PMID 7519780.
  14. ^ Kharitonenkov, A. I.; Bulgarina, T. V. (1990-06-01). "[The effect of phorbol esters and Ca2+ ions on the process of autophosphorylation of epidermal growth factor receptor in vivo]". Biokhimiia (Moscow, Russia). 55 (6): 1104–1109. ISSN 0320-9725. PMID 2207207.
  15. ^ Stein-Gerlach, M.; Kharitonenkov, A.; Vogel, W.; Ali, S.; Ullrich, A. (1995-10-20). "Protein-tyrosine phosphatase 1D modulates its own state of tyrosine phosphorylation". The Journal of Biological Chemistry. 270 (42): 24635–24637. doi:10.1074/jbc.270.42.24635. ISSN 0021-9258. PMID 7559570.
  16. ^ Kharitonenkov, A.; Schnekenburger, J.; Chen, Z.; Knyazev, P.; Ali, S.; Zwick, E.; White, M.; Ullrich, A. (1995-12-08). "Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction". The Journal of Biological Chemistry. 270 (49): 29189–29193. doi:10.1074/jbc.270.49.29189. ISSN 0021-9258. PMID 7493946.
  17. ^ Ali, S.; Chen, Z.; Lebrun, J. J.; Vogel, W.; Kharitonenkov, A.; Kelly, P. A.; Ullrich, A. (1996-01-02). "PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation". The EMBO Journal. 15 (1): 135–142. doi:10.1002/j.1460-2075.1996.tb00341.x. ISSN 0261-4189. PMC 449925. PMID 8598196.
  18. ^ Kharitonenkov, Alexei; Adams, Andrew C. (2014-06-01). "Inventing new medicines: The FGF21 story". Molecular Metabolism. 3 (3): 221–229. doi:10.1016/j.molmet.2013.12.003. ISSN 2212-8778. PMC 3986619. PMID 24749049.
  19. ^ Kharitonenkov, Alexei; DiMarchi, Richard (2015-11-01). "FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties". Trends in Endocrinology and Metabolism. 26 (11): 608–617. doi:10.1016/j.tem.2015.09.007. ISSN 1879-3061. PMID 26490383. S2CID 3696213.
  20. ^ Taylor, Nick Paul (2015-08-28). "Novo Nordisk buys diabetes startups founded by Lilly R&D veteran". Fierce Biotech. Retrieved 2022-12-01.
  21. ^ Agrawal, Archita; Parlee, Sebastian; Perez-Tilve, Diego; Li, Pengyun; Pan, Jia; Mroz, Piotr A.; Kruse Hansen, Ann Maria; Andersen, Birgitte; Finan, Brian; Kharitonenkov, Alexei; DiMarchi, Richard D. (2018-07-01). "Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity". Molecular Metabolism. 13: 45–55. doi:10.1016/j.molmet.2018.05.003. ISSN 2212-8778. PMC 6026317. PMID 29789271.
  22. ^ Pan, Jia; Parlee, Sebastian D.; Brunel, Florence M.; Li, Pengyun; Lu, Wei; Perez-Tilve, Diego; Liu, Fa; Finan, Brian; Kharitonenkov, Alexei; DiMarchi, Richard D. (2020-10-09). "Optimization of Peptide Inhibitors of β-Klotho as Antagonists of Fibroblast Growth Factors 19 and 21". ACS Pharmacology & Translational Science. 3 (5): 978–986. doi:10.1021/acsptsci.0c00100. ISSN 2575-9108. PMC 7551714. PMID 33073195.
  23. ^ "News and events". Alpha Young. Retrieved 2022-12-01.
  24. ^ "Biotech Consulting | AKbiotech". AK biotechnologies. Retrieved 2022-12-01.
  25. ^ "Alexei Kharitonenkov Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2022-11-28.
  26. ^ a b c d e f "Google Scholar". scholar.google.es. Retrieved 2022-12-01.
  27. ^ Micanovic, Radmila; Dunbar, James D.; Kharitonenkov, Alexei (2011-04-08), Wang, Minghan (ed.), "Fibroblast Growth Factor 21 as a Novel Metabolic Regulator", Metabolic Syndrome, Hoboken, NJ, USA: John Wiley & Sons, Inc., pp. 377–389, doi:10.1002/9780470910016.ch14, ISBN 978-0-470-91001-6, retrieved 2022-11-28
  28. ^ Zhao, Yang; Dunbar, James D.; Kharitonenkov, Alexei (2012), Kuro-o, Makoto (ed.), "FGF21 as a Therapeutic Reagent", Endocrine FGFs and Klothos, vol. 728, New York, NY: Springer US, pp. 214–228, doi:10.1007/978-1-4614-0887-1_14, ISBN 978-1-4614-0886-4, PMID 22396172, retrieved 2022-11-28
  29. ^ a b Kharitonenkov, Alexei; Shiyanova, Tatiyana L.; Koester, Anja; Ford, Amy M.; Micanovic, Radmila; Galbreath, Elizabeth J.; Sandusky, George E.; Hammond, Lisa J.; Moyers, Julie S.; Owens, Rebecca A.; Gromada, Jesper; Brozinick, Joseph T.; Hawkins, Eric D.; Wroblewski, Victor J.; Li, De-Shan (2005-06-01). "FGF-21 as a novel metabolic regulator". The Journal of Clinical Investigation. 115 (6): 1627–1635. doi:10.1172/JCI23606. ISSN 0021-9738. PMC 1088017. PMID 15902306.
  30. ^ "Alexei Kharitonenkov Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2023-09-07.
  31. ^ "Alexei Kharitonenkov". Researchgate.
  32. ^ Adams, Andrew C.; Halstead, Carolyn A.; Hansen, Barbara C.; Irizarry, Armando R.; Martin, Jennifer A.; Myers, Sharon R.; Reynolds, Vincent L.; Smith, Holly W.; Wroblewski, Victor J.; Kharitonenkov, Alexei (2013). "LY2405319, an Engineered FGF21 Variant, Improves the Metabolic Status of Diabetic Monkeys". PLOS ONE. 8 (6): e65763. Bibcode:2013PLoSO...865763A. doi:10.1371/journal.pone.0065763. ISSN 1932-6203. PMC 3688819. PMID 23823755.
  33. ^ Pan, Qi; Lin, Shushan; Li, Yu; Liu, Liang; Li, Xiaoping; Gao, Xianglei; Yan, Jiangyu; Gu, Baohua; Chen, Xiaofeng; Li, Wenjia; Tang, Xinfa; Chen, Chao; Guo, Lixin (2021-01-01). "A novel GLP-1 and FGF21 dual agonist has therapeutic potential for diabetes and non-alcoholic steatohepatitis". eBioMedicine. 63: 103202. doi:10.1016/j.ebiom.2020.103202. ISSN 2352-3964. PMC 7806870. PMID 33421947.
  34. ^ Gillum, Matthew P. (2018-05-01). "Parsing the Potential Neuroendocrine Actions of FGF21 in Primates". Endocrinology. 159 (5): 1966–1970. doi:10.1210/en.2018-00208. ISSN 1945-7170. PMID 29608670. S2CID 4706864.
  35. ^ Jackson, V. Margaret; Breen, Danna M.; Fortin, Jean-Philippe; Liou, Alice; Kuzmiski, J. Brent; Loomis, A. Katrina; Rives, Marie-Laure; Shah, Bhavik; Carpino, Philip A. (2015). "Latest approaches for the treatment of obesity". Expert Opinion on Drug Discovery. 10 (8): 825–839. doi:10.1517/17460441.2015.1044966. ISSN 1746-045X. PMID 25967138. S2CID 40507446.
  36. ^ Müller, Timo D.; Blüher, Matthias; Tschöp, Matthias H.; DiMarchi, Richard D. (2022-03-01). "Anti-obesity drug discovery: advances and challenges". Nature Reviews. Drug Discovery. 21 (3): 201–223. doi:10.1038/s41573-021-00337-8. ISSN 1474-1784. PMC 8609996. PMID 34815532.
  37. ^ "Behavioral Approaches to the Treatment of Obesity", Handbook of Obesity, CRC Press, pp. 162–183, 2003-12-05, doi:10.1201/b14234-12, ISBN 978-0-429-16450-7, retrieved 2023-01-20
  38. ^ Adams, Andrew C.; Yang, Chaofeng; Coskun, Tamer; Cheng, Christine C.; Gimeno, Ruth E.; Luo, Yongde; Kharitonenkov, Alexei (2012). "The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue". Molecular Metabolism. 2 (1): 31–37. doi:10.1016/j.molmet.2012.08.007. ISSN 2212-8778. PMC 3757657. PMID 24024127.
  39. ^ Adams, Andrew C.; Cheng, Christine C.; Coskun, Tamer; Kharitonenkov, Alexei (2012). "FGF21 requires βklotho to act in vivo". PLOS ONE. 7 (11): e49977. Bibcode:2012PLoSO...749977A. doi:10.1371/journal.pone.0049977. ISSN 1932-6203. PMC 3507945. PMID 23209629.
  40. ^ Yang, Chaofeng; Jin, Chengliu; Li, Xiaokun; Wang, Fen; McKeehan, Wallace L.; Luo, Yongde (2012). "Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB". PLOS ONE. 7 (3): e33870. Bibcode:2012PLoSO...733870Y. doi:10.1371/journal.pone.0033870. ISSN 1932-6203. PMC 3307775. PMID 22442730.
  41. ^ Aljohani, Ahmed; Khan, Mohammad Imran; Bonneville, Abram; Guo, Changan; Jeffery, Justin; O'Neill, Lucas; Syed, Deeba Nadeem; Lewis, Sarah A.; Burhans, Maggie; Mukhtar, Hasan; Ntambi, James M. (2019-12-20). "Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α-FGF21 axis in mice". The Journal of Biological Chemistry. 294 (51): 19475–19485. doi:10.1074/jbc.RA119.009868. ISSN 1083-351X. PMC 6926457. PMID 31690632.
  42. ^ Bookout, Angie L.; de Groot, Marleen H. M.; Owen, Bryn M.; Lee, Syann; Gautron, Laurent; Lawrence, Heather L.; Ding, Xunshan; Elmquist, Joel K.; Takahashi, Joseph S.; Mangelsdorf, David J.; Kliewer, Steven A. (2013-09-01). "FGF21 regulates metabolism and circadian behavior by acting on the nervous system". Nature Medicine. 19 (9): 1147–1152. doi:10.1038/nm.3249. ISSN 1546-170X. PMC 3769420. PMID 23933984.
  43. ^ Owen, Bryn M.; Ding, Xunshan; Morgan, Donald A.; Coate, Katie Colbert; Bookout, Angie L.; Rahmouni, Kamal; Kliewer, Steven A.; Mangelsdorf, David J. (2014-10-07). "FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss". Cell Metabolism. 20 (4): 670–677. doi:10.1016/j.cmet.2014.07.012. ISSN 1932-7420. PMC 4192037. PMID 25130400.
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