Vassilios Papadopoulos

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Vassilios Papadopoulos

DPharm, PhD, DSc (hon)
Vassilios Papadopoulos.jpg
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
Spouse Martine 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

Contents

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

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]

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]

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Steroid</span> Any organic compound having sterane as a core structure

A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol (opisthokonts) or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.

Luteinizing hormone is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In females, an acute rise of LH known as an LH surge, triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell–stimulating hormone (ICSH), it stimulates Leydig cell production of testosterone. It acts synergistically with follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Steroid hormone</span> Substance with biological function

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids and sex steroids. Within those two classes are five types according to the receptors to which they bind: glucocorticoids and mineralocorticoids and androgens, estrogens, and progestogens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands.

<span class="mw-page-title-main">Leydig cell</span> Androgen-producing cell adjacent to the seminiferous tubules of the testicle

Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral in shape and have a large, prominent nucleus, an eosinophilic cytoplasm, and numerous lipid-filled vesicles.

Israel Hanukoglu is a Turkish-born Israeli scientist. He is a full professor of biochemistry and molecular biology at Ariel University and former science and technology adviser to the prime minister of Israel (1996–1999). He is founder of Israel Science and Technology Directory.

Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy.

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<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Protein-coding gene in the species Homo sapiens

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

<span class="mw-page-title-main">Cholesterol side-chain cleavage enzyme</span> Mammalian protein found in Homo sapiens

Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones.

<span class="mw-page-title-main">Translocator protein</span> Human protein

Translocator protein (TSPO) is an 18 kDa protein mainly found on the outer mitochondrial membrane. It was first described as peripheral benzodiazepine receptor (PBR), a secondary binding site for diazepam, but subsequent research has found the receptor to be expressed throughout the body and brain. In humans, the translocator protein is encoded by the TSPO gene. It belongs to a family of tryptophan-rich sensory proteins. Regarding intramitochondrial cholesterol transport, TSPO has been proposed to interact with StAR to transport cholesterol into mitochondria, though evidence is mixed.

<span class="mw-page-title-main">Emapunil</span> Chemical compound

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A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of the enzymes that are involved in the process of steroidogenesis, the biosynthesis of endogenous steroids and steroid hormones. They may inhibit the production of cholesterol and other sterols, sex steroids such as androgens, estrogens, and progestogens, corticosteroids such as glucocorticoids and mineralocorticoids, and neurosteroids. They are used in the treatment of a variety of medical conditions that depend on endogenous steroids.

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<span class="mw-page-title-main">Steroidogenic enzyme</span>

Steroidogenic enzymes are enzymes that are involved in steroidogenesis and steroid biosynthesis. They are responsible for the biosynthesis of the steroid hormones, including sex steroids and corticosteroids, as well as neurosteroids, from cholesterol. Steroidogenic enzymes are most highly expressed in classical steroidogenic tissues, such as the testis, ovary, and adrenal cortex, but are also present in other tissues in the body.

Marion Sewer (1972-2016) was a pharmacologist and professor at the University of California, San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences known for her research on steroid hormone biogenesis and her commitment to increasing diversity in science. Much of her research centered around cytochrome P450, a family of enzymes involved in the conversion of cholesterol into steroid hormones. She died unexpectedly at the age of 43 from a pulmonary embolism on January 28, 2016, while traveling through the Detroit airport.

Martine Culty is a scholar and professor at the Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences at the University of Southern California in Los Angeles, California.

References

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  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.
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  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.
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  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.
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  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.
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  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. 1 2 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. 1 2 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.{{cite web}}: CS1 maint: url-status (link)
  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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