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vassilios-papadopoulos

Vassilios Papadopoulos, PhD

Executive Director, Research Institute of the McGill University Health Centre and Professor, Faculty of Medicine, McGill University

Department: Medicine

Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Bloc E, Montreal, Quebec H4A 3J1, Canada

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Telephone : 514 934-1934, ext. 44580

Fax: 514 934-8439

Field of research:

My research focuses on understanding the cellular and molecular mechanisms responsible for the initiation and maintenance of steroid biosynthesis in the adrenal, gonads and brain, in health and disease. We also examine the regulation of steroid biosynthesis, intracellular compartmentalization and homeostasis by hormones, chemicals, drugs, natural products and environmental factors. Our goal is to understand the pathophysiology of steroidogenesis and develop new tools for the treatment of diseases related to elevated or low steroid levels or alter subcellular steroid compartmentalization as a means to block disease acquisition and/or progression. In these studies our laboratory is using biochemical, pharmacological and molecular methods as well animal models of disease and human biopsies and specimens to identify the physiological role of critical components of the steroidogenic pathway and pathological situations created by changes in the expression of these components in animals and humans. Drug design methods and molecular modeling are used to modify existing chemical entities and generate novel ones targeted at key elements of the steroidogenic machinery. Our research has direct applications in reproduction and development, cancer, stress-related disorders, aging and brain related dysfunction, such as Alzheimer’s disease pathology.

Resume of recent results:

Our research has led to greater understanding of how steroid formation is regulated, the identification of molecules targeting key elements of this process, and clinical applications with brain and testis as the target tissues. Significant contributions include:

 

 

1) We identified mechanisms of cholesterol import into mitochondria, the rate-determining step in steroidogenesis, and showed that translocator protein (TSPO), a high affinity cholesterol- and drug-binding protein, serves as an anchor for signaling molecules targeted to mitochondria.

 

 

2) We showed that inducing TSPO function by drug ligands in glial and Leydig cells led to increased neurosteroid and androgen formation, respectively, findings that may have therapeutic potential for normalizing T levels in hypogonadal men and the treatment of anxiety by neurosteroids.

 

 

3) While characterizing the ability of the brain to form steroids de novo, we identified a brain-specific pathway for the biosynthesis of the neurosteroid dehydroepiandrosterone. These results led to the development and successful lead clinical study of a novel Alzheimer’s blood diagnostic. We also found steroid intermediates with neuroprotective properties that are reduced in Alzheimer’s brain specimens, leading to the design of new drugs to treat Alzheimer’s disease..

 

 

4) Our studies of the impact of environmental factors on steroidogenesis led to the observation that gestational exposure to phthalate plasticizers reduced testosterone formation in adult rats. This led to the discovery of novel molecular targets of phthalates, including epigenetic changes that lead to altered adult adrenal and testicular function, and to adverse effects on the cardiovascular and immune systems.

Laboratory members:

 

Name 

Position

Email Address

Jinjiang Fan

Research Associate

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Daniel Arguelles Martinez

Research Associate

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Andrew Midzak

Research Associate

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Edward Daly

Research Associate

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Leeyah Issop

Post-Doctoral Fellow

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Enrico Campioli

Post-Doctoral Fellow

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Yasaman (Jasmine) Aghazadeh

Post-Doctoral Fellow

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Charles Garbis Essagian

Lab Manager

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Pushwinder Kaur

Research Assistant

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Jiehan Li

Graduate Student

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Sathvika Jagannathan

Graduate Student

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Sunghoon (Daniel) Lee

Graduate Student

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Nancy Li

Undergraduate Student

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Publications (selection):

Representative publications published since in the last 5 years:

  • Fan J, Midzak A, Campioli E, Culty M, Papadopoulos V (2015) Conditional steroidogenic cell-targeted deletion of the translocator protein (TSPO, 18-kDa) unveil its crucial role in viability and hormone-dependent steroid formation. Proc Natl Acad Sci USA, in press.
  • Campioli E, Duong TB, Deschamps F, Papadopoulos V (2015) Cyclohexane-1, 2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue. Environmental Res, 140:145-156.
  • Martinez–Arguelles DB, Papadopoulos V (2015) Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate. Endocrinology, 156:124-133.
  • Issop L, Fan J, Lee S, Rone MB, Basu K, Mui J, Papadopoulos V (2015) Mitochondria-associated membrane formation in hormone-stimulated Leydig cell steroidogenesis: Role of ATAD3. Endocrinology, 156:334-345.
  • Martinez–Arguelles DB, Campioli E, Lienhart C, Fan J, Culty M, Zirkin BR, Papadopoulos V (2014) In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate induces long-term changes in gene expression in the adult male adrenal gland. Endocrinology, 155:1667-1678.
  • Aghazadeh Y, Martinez-Arguelles DB, Fan J, Culty M, Papadopoulos V (2014) Induction of androgen formation in the male by a TAT-VDAC1 fusion peptide blocking 14-3-3ε protein adaptor and mitochondrial VDAC1 interactions. Molecular Therapy (Nature), 22:1779-1791.
  • Rone M, Midzak A, Issop L, Rammouz G, Jagannathan S, Fan J, Blonder J, Ye X, Veenstra TD, Papadopoulos V (2012) Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocr, 26:1868-1882
  • Fan J, Lindemann P, Feuilloley M, Papadopoulos V (2012) Structural and functional evolution of the translocator protein (18 kDa). Curr Mol Medicine, 12:369-386.
  • Fan J, Traore, K, Li W, Amri H, Huang H, Wu C, Chen H, Zirkin B, Papadopoulos V (2010) Molecular mechanisms mediating the effect of mono- (2-ethylhexyl) phthalate (MEHP) on hormone-stimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology, 151:3348-3362.
  • Lecanu L, McCourty A, Sidahmed EK, Greeson J, Papadopoulos V (2010) Caprospinol reduces amyloid deposits and restores cognitive function. Neuroscience, 165:427-435.
  • Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, Adams D, Groyer G, Schumacher M (2010) Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nature Drug Discov Rev, 9:971-988.
  • Fan J, Rone MB, Papadopoulos V (2009) Translocator Protein 2 (TSPO2) is involved in cholesterol redistribution during erythropoiesis. J Biol Chem, 284:30484-30497.
  • Li J, Daly E, Campioli, E, Wabish M, Papadopoulos V (2014) De novo synthesis of steroids and oxysterols in adipocytes. J Biol Chem, 289:747-764.
  • Rammouz G, Lecanu L, Aisen P, Papadopoulos V (2011) A lead study on oxidative stress-mediated dehydroepiandrosterone formation in serum: the biochemical basis for a diagnosis of Alzheimer's disease. J Alzheim Dis, 24 (2):5-16.

Awards:

  • Gold Medal Award from the City of Athens, Greece (1978)
  • Sandoz Award, Endocrine Society of Australia (1988)
  • James Shannon Director’s Award from NIDDK, NIH, USA (1991-1993)
  • Research Career Development Award, NICHD, NIH, USA (1993-1998)
  • Elected Corresponding Member of the French National Academy of Pharmacy; pharmacological sciences section (2002)
  • Biotechnology Leadership Award, Georgetown University (2004)
  • EVOL (Education & Volunteers) Visionary Leadership Award, Georgetown University (2007)
  • Canada Research Chair (tier 1) in Biochemical Pharmacology (2007-2021)
  • Elected Corresponding Member of the French National Academy of Medicine; biological and pharmaceutical sciences section (2008)
  • Larry Ewing Lecture in Reproductive Biology; Johns Hopkins University School of Public Health (2008)
  • Dean’s Distinguished Lecture; Georgetown University Medical Center (2009)
  • Elected Fellow of the American Association for the Advancement of Science (AAAS), Section on Medical Sciences (2009)
  • Dr. Phil Gold Chair in Medicine supported by a McGill-MUHC endowment (2010)
  • Elected Fellow of the Canadian Academy of Health Sciences (CAHS) (2011)
  • Elected Fellow of The International College of Neuropsychopharmacology (2011)
  • Prize Michel Sarrazin awarded by the Club de recherches cliniques du Quebec (2013)
  • President, American Society of Andrology (2015-16)

Our research has led to over 300 refereed papers and book chapters. Our publications have been cited over 14,500 times (h-index 63), and the research has led to 44 patents and 3 commercialized products. Materials and animal models developed through our work have been shared freely with almost 200 laboratories worldwide.