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 disruptingphthalates 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]
^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. ISSN0022-4731. PMID3736047.
^ abPapadopoulos, 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. ISSN0022-0795. PMID3668435.
^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. ISSN0303-7207. PMID2546840. S2CID42634068.
^"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. ISSN1351-0088. PMID12790773.
^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. ISSN0270-4137. PMID26841972. S2CID20325244.
^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. ISSN0021-972X. PMID2026754.
^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. ISSN0036-8075. PMID7777858.
^ abRupprecht, 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. ISSN1474-1776. PMID21119734. S2CID23296183.
^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. ISSN1875-8908. PMID21335661.
^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. ISSN0953-8194. PMID21623958. S2CID24032303.