Vassilios Papadopoulos

Vassilios Papadopoulos, DPharm, PhD, DSc (hon), born February 18, 1961, in Athens, Greece, is a scholar, researcher, inventor, professor, and university administrator who has served as dean of the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences at the University of Southern California in Los Angeles, California since 2016.[1] Previously, he was the associate vice president and director of the Biomedical Graduate Research Organization at Georgetown University from 2005 to 2007, and the executive director and chief scientific officer of the Research Institute of the McGill University Health Center from 2007 to 2015.[2]

Vassilios Papadopoulos

DPharm, PhD, DSc (hon)
Dean, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences
BornFebruary 18th, 1961
Athens, Greece
TitleDean, USC Mann School
John Stauffer Dean’s Chair in Pharmaceutical Sciences
Professor of Pharmacology and Pharmaceutical Sciences
SpouseMartine Culty
Academic background
EducationDegree in Pharmacy (DPharm), University of Athens, Athens, Greece

Doctorate Degree of Health and Life Sciences (PhD), University Pierre and Marie Curie, Paris, France

Postdoctoral fellow, Department of Biochemistry, Faculty of Medicine, C.N.R.S., (National Center of Scientific Research), Centre Hospitalier Universitaire, Caen, France

Post-doctoral fellow, National Health and Medical Research Council (NHMRC), Department of Endocrinology, The Prince of Wales Hospital, The University of New South Wales, Wales, Australia

Degree of Extensive Studies (MSc) in Animal Biology and Physiology, University Pierre and Marie Curie, Paris, France

Education

Papadopoulos holds a degree in pharmacy (DPharm) from University of Athens in 1982 before completing his PhD at Université Pierre et Marie Curie in Paris (Doctor in Pharmacy) in 1984.[2][1] Papadopoulos continued his education as a post-doctoral researcher in France and Australia thereafter.[2]

During his studies in pharmacy, Papadopoulos performed research at the Institute of Biological Research and Biotechnology, National Hellenic Research foundation in Athens, Greece where he focused on adrenal function, steroid hormones, and steroid receptors.[2] At Université Pierre et Marie Curie, Papadopoulos engaged in research on estrogen production by Leydig cells and the paracrine regulation of Leydig cell function.[3][4] Afterwards, Papadopoulos completed postdoctoral training at Prince of Wales Hospital, University of New South Wales, Sydney, Australia, researching the role of kinases and phosphatases in cholesterol transport and steroidogenesis.[5][6]

Career and research

Vassilios has published more than 300 papers and holds numerous patents.[7] Papadopoulos has served on advisory committees as an industry leader and expert. He holds membership in the National Academies of Medicine and Pharmacy in France, is a fellow of the American Association for the Advancement of Science, the American Association of Pharmaceutical Scientists (AAPS), and the Canadian Academy of Health Sciences.[7]

Papadopoulos’ research focuses the cellular and molecular mechanisms responsible for the initiation and maintenance of steroid hormones in health and disease.[7] He also examines the regulation of steroid biosynthesis,[8] intracellular compartmentalization and homeostasis by hormones,[9] chemicals, drugs, natural products and environmental factors.[10] Additional research has focused on neurosteroids in the brain,[11] adipose tissue,[12] and nonalcoholic fatty liver disease.[13]

In 1988, Papadopoulos was appointed to the faculty of Georgetown University School of Medicine[2] where he continued research on the regulation of steroidogenesis to identify the mechanisms of action of DBI on mitochondrial steroid formation in steroidogenic cells.[14][15] Later, Papadopoulos worked in collaboration with Patrizia Guarneri demonstrating that brain neurosteroid synthesis is under the control of translocator protein (TSPO) drug ligands and endogenous DBI,[16] leading to the first pharmacological means to regulate steroid formation in the brain.[17] His research on steroidogenesis continued at McGill, focusing on the mechanisms of mitochondrial cholesterol import[8] and the synthesis of steroids and oxysterols in adipocytes[18] and prostate.[19] At USC his research focuses on Leydig cell development[20] and the role of TSPO in non-alcoholic fatty liver disease.[21]

Contributions to Science

Steroidogenesis

Papadopoulos' studies demonstrated that the development of Leydig cells and their ability to produce testosterone are controlled by intratesticular factors,[4][22][23] and that TSPO is a high-affinity cholesterol and drug-binding protein which controls the rate of steroid formation in rodents and humans.[8][24] Moreover, luteinizing hormone binding to Leydig cells' luteinizing hormone receptors induces the formation of a cytosolic and mitochondrial protein complex involved in cholesterol targeting to cytochrome P450 family 11 subfamily A member 1 (CYP11A1) in the mitochondria. This focus on steroidogenesis revealed the mitochondrial protein complex that drives cholesterol import, trafficking, and metabolism for steroid hormone production.[24] The identification of the protein complex has led to molecular strategies to which increase steroid hormone formation.[24][25]

Neurosteroid formation

Papadopoulos' neurosteroid research on inducing TSPO via drug ligands in glial cells increased neurosteroid formation and led to therapeutic application for the treatment of anxiety and other mental health pathologies.[26] Thereafter, TSPO drug ligands reached the market for the treatment of anxiety and other neuropsychiatric disorders and neurological diseases.[2][26] Currently, several TSPO ligands are in clinical development for neurological disorders, neuropsychiatric diseases, and cancer.[2] Moreover, the identification of a brain-specific pathway for dehydroepiandrosterone steroid synthesis led to the development of a novel Alzheimer's blood diagnostic[27] and the design of neuroprotective drugs.[28]

Endocrine disrupting chemicals

At Georgetown, studies on in utero and adult in vivo exposure to endocrine disrupting phthalates and plasticizers with collaborator Martine Culty revealed an impact on testicular function.[29] Endocrine disrupting chemicals such as phthalate DEHP and the non-phthalate DINCH reduced testosterone and aldosterone formation in adult rats.[29][10][30] This work contributed to the body of evidence on the endocrine disrupting potential of plasticizers and their regulation by governmental agencies.[2]

Administrative career

Between 2004 and 2007, Papadopoulos was the Associate Vice President for Research at Georgetown University Medical Center, and subsequently appointed the Director of Biomedical Graduate Research Organization.[2][1] Under Papadopoulos' direction, the institution obtained an NIH-funded General Clinical Research Center and its first Clinical and Translational Science Award. Papadopoulos served from 2007 to 2016 as the executive director and chief scientific officer of the Research Institute of the McGill University Health Centre (RI-MUHC), one of Canada's largest research centers.[2] At the RI-MUHC he was a professor in the faculty of medicine at McGill University and held a Canada Research Chair in Biochemical Pharmacology and the Phil Gold Chair in Medicine at McGill and the MUHC.[2] Under Papadopoulos' tenure, more than $300 million federal and provincial grants were raised, resulting in the creating of a state-of-the-art clinical and biomedical research facility.[31]

Since 2016, Papadopoulos has served as dean of the Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences at University of Southern California, previously known as USC School of Pharmacy.[32] In 2022, USC announced the $50 million renaming gift for the endowment of the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, the largest gift for pharmacy school in California.[33]

References
  1. "Vassilios Papadopoulos, DPharm, PhD, DSc (hon)". USC Schaeffer. Retrieved 2023-03-10.
  2. Yan, Wei (2021-11-15). "An interview with Dr. Vassilios Papadopoulos". Biology of Reproduction. 105 (5): 1070–1074. doi:10.1093/biolre/ioab137. ISSN 0006-3363. PMID 34341822.
  3. Papadopoulos, V.; Carreau, S.; Szerman-Joly, E.; Drosdowsky, M.A.; Dehennin, L.; Scholler, R. (June 1986). "Rat testis 17β-estradiol: Identification by gas chromatography-mass spectrometry and age related cellular distribution". Journal of Steroid Biochemistry. 24 (6): 1211–1216. doi:10.1016/0022-4731(86)90385-7. ISSN 0022-4731. PMID 3736047.
  4. Papadopoulos, V.; Kamtchouing, P.; Drosdowsky, M. A.; de Reviers, M. T. Hochereau; Carreau, S. (September 1987). "Adult rat Sertoli cells secrete a factor or factors which modulate Leydig cell function". Journal of Endocrinology. 114 (3): 459–467. doi:10.1677/joe.0.1140459. ISSN 0022-0795. PMID 3668435.
  5. Papadopoulos, V; Hall, P F (1989-02-01). "Isolation and characterization of protein kinase C from Y-1 adrenal cell cytoskeleton". Journal of Cell Biology. 108 (2): 553–567. doi:10.1083/jcb.108.2.553. ISSN 0021-9525. PMC 2115438. PMID 2918025.
  6. Papadopoulos, Vassilios; Brown, A.Shane; Hall, Peter F. (May 1989). "Isolation and characterisation of calcineurin from adrenal cell cytoskeleton: identification of substrates for Ca2+-calmodulin-dependent phosphatase activity". Molecular and Cellular Endocrinology. 63 (1–2): 23–38. doi:10.1016/0303-7207(89)90078-6. ISSN 0303-7207. PMID 2546840. S2CID 42634068.
  7. "Vassilios Papadopoulos, DPharm, PhD, DSc (Hon)". USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences. Retrieved 2023-03-10.
  8. Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Ye, Xiaoying; Blonder, Josip; Veenstra, Timothy; Papadopoulos, Vassilios (2012-11-01). "Identification of a Dynamic Mitochondrial Protein Complex Driving Cholesterol Import, Trafficking, and Metabolism to Steroid Hormones". Molecular Endocrinology. 26 (11): 1868–1882. doi:10.1210/me.2012-1159. ISSN 0888-8809. PMC 5416962. PMID 22973050. S2CID 21525902.
  9. "Proceedings of the International Congress on Hormonal Steroids and Hormones and Cancer. 21-25 October 2002, Fukuoka, Japan". Endocrine-Related Cancer. 10 (2): 109–345. June 2003. doi:10.1677/erc.0.0100109. ISSN 1351-0088. PMID 12790773.
  10. Martinez-Arguelles, Daniel B.; Papadopoulos, Vassilios (2015-03-04). "Mechanisms Mediating Environmental Chemical-Induced Endocrine Disruption in the Adrenal Gland". Frontiers in Endocrinology. 6: 29. doi:10.3389/fendo.2015.00029. ISSN 1664-2392. PMC 4349159. PMID 25788893.
  11. Lin, Yiqi Christina; Cheung, Garett; Porter, Edith; Papadopoulos, Vassilios (July 2022). "The neurosteroid pregnenolone is synthesized by a mitochondrial P450 enzyme other than CYP11A1 in human glial cells". Journal of Biological Chemistry. 298 (7): 102110. doi:10.1016/j.jbc.2022.102110. ISSN 0021-9258. PMC 9278081. PMID 35688208.
  12. Campioli, Enrico; Duong, Tam B.; Deschamps, François; Papadopoulos, Vassilios (July 2015). "Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue". Environmental Research. 140: 145–156. Bibcode:2015ER....140..145C. doi:10.1016/j.envres.2015.03.036. PMID 25863588.
  13. Li, Yuchang; Chen, Liting; Li, Lu; Sottas, Chantal; Petrillo, Stephanie K.; Lazaris, Anthoula; Metrakos, Peter; Wu, Hangyu; Ishida, Yuji; Saito, Takeshi; Golden-Mason, Lucy; Rosen, Hugo R.; Wolff, Jeremy J.; Silvescu, Cristina I.; Garza, Samuel (May 2021). "Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease". iScience. 24 (5): 102457. Bibcode:2021iSci...24j2457L. doi:10.1016/j.isci.2021.102457. PMC 8113880. PMID 34013171.
  14. Krueger, K.E.; Papadopoulos, V. (September 1990). "Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells". Journal of Biological Chemistry. 265 (25): 15015–15022. doi:10.1016/s0021-9258(18)77217-7. ISSN 0021-9258. PMID 2168398.
  15. Papadopoulos, V; Mukhin, A G; Costa, E; Krueger, K E (March 1990). "The peripheral-type benzodiazepine receptor is functionally linked to Leydig cell steroidogenesis". Journal of Biological Chemistry. 265 (7): 3772–3779. doi:10.1016/s0021-9258(19)39661-9. ISSN 0021-9258. PMID 2154488.
  16. Papadopoulos, V; Guarneri, P; Kreuger, K E; Guidotti, A; Costa, E (June 1992). "Pregnenolone biosynthesis in C6-2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor". Proceedings of the National Academy of Sciences. 89 (11): 5113–5117. Bibcode:1992PNAS...89.5113P. doi:10.1073/pnas.89.11.5113. ISSN 0027-8424. PMC 49239. PMID 1317581.
  17. Costa, E.; Auta, J.; Guidotti, A.; Korneyev, A.; Romeo, E. (June 1994). "The pharmacology of neurosteroidogenesis". The Journal of Steroid Biochemistry and Molecular Biology. 49 (4–6): 385–389. doi:10.1016/0960-0760(94)90284-4. ISSN 0960-0760. PMID 8043504. S2CID 33492066.
  18. Li, Jiehan; Daly, Edward; Campioli, Enrico; Wabitsch, Martin; Papadopoulos, Vassilios (January 2014). "De Novo Synthesis of Steroids and Oxysterols in Adipocytes". Journal of Biological Chemistry. 289 (2): 747–764. doi:10.1074/jbc.m113.534172. ISSN 0021-9258. PMC 3887202. PMID 24280213.
  19. Sakai, Monica; Martinez-Arguelles, Daniel B.; Aprikian, Armen G.; Magliocco, Anthony M.; Papadopoulos, Vassilios (2016-02-04). "De novo steroid biosynthesis in human prostate cell lines and biopsies". The Prostate. 76 (6): 575–587. doi:10.1002/pros.23146. ISSN 0270-4137. PMID 26841972. S2CID 20325244.
  20. Li, Lu; Li, Yuchang; Sottas, Chantal; Culty, Martine; Fan, Jinjiang; Hu, Yiman; Cheung, Garett; Chemes, Héctor E.; Papadopoulos, Vassilios (2019-10-07). "Directing differentiation of human induced pluripotent stem cells toward androgen-producing Leydig cells rather than adrenal cells". Proceedings of the National Academy of Sciences. 116 (46): 23274–23283. Bibcode:2019PNAS..11623274L. doi:10.1073/pnas.1908207116. ISSN 0027-8424. PMC 6859353. PMID 31591190.
  21. Li, Yuchang; Chen, Liting; Li, Lu; Sottas, Chantal; Petrillo, Stephanie K.; Lazaris, Anthoula; Metrakos, Peter; Wu, Hangyu; Ishida, Yuji; Saito, Takeshi; Golden-Mason, Lucy; Rosen, Hugo R.; Wolff, Jeremy J.; Silvescu, Cristina I.; Garza, Samuel (May 2021). "Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease". iScience. 24 (5): 102457. Bibcode:2021iSci...24j2457L. doi:10.1016/j.isci.2021.102457. ISSN 2589-0042. PMC 8113880. PMID 34013171. S2CID 234778454.
  22. PAPADOPOULOS, VASSILIOS (June 1991). "Identification and Purification of a Human Sertoli Cell- Secreted Protein (hSCSP-80)Stimulating Leydig Cell Steroid Biosynthesis". The Journal of Clinical Endocrinology & Metabolism. 72 (6): 1332–1339. doi:10.1210/jcem-72-6-1332. ISSN 0021-972X. PMID 2026754.
  23. Boujrad, Noureddine; Ogwuegbu, Stephen O.; Garnier, Martine; Lee, Choong-Hyun; Martin, Brian M.; Papadopoulos, Vassilios (1995-06-16). "Identification of a Stimulator of Steroid Hormone Synthesis Isolated from Testis". Science. 268 (5217): 1609–1612. Bibcode:1995Sci...268.1609B. doi:10.1126/science.7777858. ISSN 0036-8075. PMID 7777858.
  24. Liu, Jun; Rone, Malena B.; Papadopoulos, Vassilios (December 2006). "Protein-Protein Interactions Mediate Mitochondrial Cholesterol Transport and Steroid Biosynthesis". Journal of Biological Chemistry. 281 (50): 38879–38893. doi:10.1074/jbc.m608820200. ISSN 0021-9258. PMID 17050526.
  25. Aghazadeh, Yasaman; Martinez-Arguelles, Daniel B; Fan, Jinjiang; Culty, Martine; Papadopoulos, Vassilios (October 2014). "Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions". Molecular Therapy. 22 (10): 1779–1791. doi:10.1038/mt.2014.116. ISSN 1525-0016. PMC 4428399. PMID 24947306.
  26. Rupprecht, Rainer; Papadopoulos, Vassilios; Rammes, Gerhard; Baghai, Thomas C.; Fan, Jinjiang; Akula, Nagaraju; Groyer, Ghislaine; Adams, David; Schumacher, Michael (December 2010). "Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders". Nature Reviews Drug Discovery. 9 (12): 971–988. doi:10.1038/nrd3295. ISSN 1474-1776. PMID 21119734. S2CID 23296183.
  27. Rammouz, Georges; Lecanu, Laurent; Aisen, Paul; Papadopoulos, Vassilios (2011-04-22). "A Lead Study on Oxidative Stress-Mediated Dehydroepiandrosterone Formation in Serum: The Biochemical Basis for a Diagnosis of Alzheimer's Disease". Journal of Alzheimer's Disease. 24 (s2): 5–16. doi:10.3233/jad-2011-101941. ISSN 1875-8908. PMID 21335661.
  28. Papadopoulos, V.; Lecanu, L. (2011-12-20). "Caprospinol: Discovery of a Steroid Drug Candidate to Treat Alzheimer's Disease Based on 22R-Hydroxycholesterol Structure and Properties". Journal of Neuroendocrinology. 24 (1): 93–101. doi:10.1111/j.1365-2826.2011.02167.x. ISSN 0953-8194. PMID 21623958. S2CID 24032303.
  29. Culty, Martine; Thuillier, Raphael; Li, Wenping; Wang, Yan; Martinez-Arguelles, Daniel B.; Benjamin, Carolina Gesteira; Triantafilou, Kostantinos M.; Zirkin, Barry R.; Papadopoulos, Vassilios (2008-06-01). "In Utero Exposure to Di-(2-ethylhexyl) Phthalate Exerts Both Short-Term and Long-Lasting Suppressive Effects on Testosterone Production in the Rat1". Biology of Reproduction. 78 (6): 1018–1028. doi:10.1095/biolreprod.107.065649. ISSN 0006-3363. PMID 18322279.
  30. Campioli, Enrico; Lee, Sunghoon; Lau, Matthew; Marques, Lucas; Papadopoulos, Vassilios (2017-09-11). "Effect of prenatal DINCH plasticizer exposure on rat offspring testicular function and metabolism". Scientific Reports. 7 (1): 11072. Bibcode:2017NatSR...711072C. doi:10.1038/s41598-017-11325-7. ISSN 2045-2322. PMC 5593853. PMID 28894178.
  31. "Vassilios Papadopoulos, DPharm, PhD, DSc (hon)". USC Schaeffer. Retrieved 2023-03-11.
  32. "Vassilios Papadopoulos". 2023-04-26.
  33. "USC School of Pharmacy announces $50 million naming gift". USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences. 2022-11-17. Retrieved 2023-03-11.
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