steroids • neurosteroids • pharmacology • drug discovery • endocrinology
My research focuses on understanding the cellular and molecular mechanisms responsible for the initiation and maintenance of steroid biosynthesis in the gonads, adrenal, and brain, in health and disease. We also study the regulation of steroid biosynthesis, intracellular compartmentalization of cholesterol by hormones, chemicals, drugs and environmental factors. Our goals are to understand the pathophysiology of steroidogenesis, develop new tools for the treatment of diseases related to elevated or low steroid levels, and alter subcellular steroid compartmentalization as a means to block disease acquisition and/or its progression. In these studies, we use biochemical, pharmacological, and molecular methods, as well animal models of disease and human specimens, to identify the pathophysiological role of critical components of the steroidogenic pathway. Drug design methods and molecular modeling help us modify existing chemical entities and generate novel ones targeted at key elements of the steroidogenic machinery.
Fan J, Campioli E, Midzak A, Culty M, Papadopoulos V. Conditional steroidogenic cell-targeted deletion of TSPO unveils a crucial role in viability and hormone-dependent steroid formation. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7261-6. PMID: 26039990.
Martinez-Arguelles DB, Papadopoulos V. 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. 2015 Jan;156(1):124-33. PMID: 25330100.
Aghazadeh Y, Ye X, Blonder J, Papadopoulos V. Protein modifications regulate the role of 14-3-3γ adaptor protein in cAMP-induced steroidogenesis in MA-10 Leydig cells. J Biol Chem. 2014 Sep 19;289(38):26542-53. PMID: 25086053.
Rone MB, Midzak AS, Issop L, Rammouz G, Jagannathan S, Fan J, Ye X, Blonder J, Veenstra T, Papadopoulos V. Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocrinol. 2012;26:1868-82. PMID: 22973050.
Rammouz G, Lecanu L, Aisen P, Papadopoulos V. A lead study on oxidative stress-mediated dehydroepiandrosterone formation in serum: the biochemical basis for a diagnosis of Alzheimer's disease. J Alzheimers Dis. 2011;24:5-16. PMID: 21335661.