Department of Biomedical Engineering
Chaitali Ghosh, Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-0559
Fax: (216) 444-9198
Our laboratory investigates the role of the blood-brain barrier in health and disease. Our studies focus on cerebrovascular research to better understand brain physiology and function in neurological disorders (e.g., epilepsy and epilepsy with other comorbidities such as stroke, depression). In much of our current work, we investigate the mechanisms and pathophysiological alterations that could possibly impede drug bioavailability across the dysfunctional blood-brain barrier. We study drug-metabolizing enzymes (e.g., cytochrome P450 enzyme, UDP-glucuronosyltransferase); transporters (e.g., P-glycoprotein/MDR1, multidrug resistance-associated proteins); nuclear receptors (e.g., glucocorticoid nuclear receptor, pregnane xenobiotic nuclear receptor), and other regulatory factors that control pharmacokinetic and pharmacodynamic phenomena during drug biotransformation in disease states. With a multidisciplinary team of clinicians, neurosurgeons, and neuroscientists, we investigate the factors contributing to drug resistance in patients suffering from epilepsy. We use multifaceted approaches to test drugs and identify their metabolites. For this, we use a humanized dynamicin vitroneurovascular unit, established with primary brain cells. We simultaneously compare drug-metabolite levels in the blood and in resected brain tissue post epilepsy surgery byin situ/ex vivoapproaches. Standardized cellular, molecular, immunological, imaging and analytical techniques are followed routinely in the laboratory. The long-term goal of these studies is to develop a screening platform for pharmacological compounds including drugs across the blood-brain barrier as a disease-modeling tool to improve drug therapy and to minimize harmful side effects brought on by the interaction of co-prescribed drugs.
FUNDING: We thank the National Institutes of Health (NINDS, NCATS), Brain & Behavior Research Foundation (formerly NARSAD), American Heart Association, and Alternatives Research & Development Foundation for their support of this work.
- Ghosh C, Hossain M, Solanki J, Najm IM, Marchi N, Janigro D. Overexpression of pregnane X and glucocorticoid receptors and the regulation of cytochrome P450 in human epileptic brain endothelial cells. Epilepsia 2017 Feb 15. doi: 10.1111/epi.13703. [Epub ahead of print].
- Banjara M, Ghosh C. Sterile Neuroinflammation and Strategies for Therapeutic Intervention. Int J Inflam 2017;2017:8385961. doi: 10.1155/2017/8385961.
- Ghosh C, Hossain M, Solanki J, Dadas A, Marchi N, Janigro D. Pathophysiological implications of neurovascular P450 in brain disorders. Drug Discov Today 2016 Oct;21(10):1609-1619. doi: 10.1016/j.drudis.2016.06.004.
- Ghosh C, Hossain M, Spriggs A, Ghosh A, Grant GA, Marchi N, Perucca E, Janigro D. Sertraline-induced potentiation of the CYP3A4-dependent neurotoxicity of carbamazepine: an in vitro study. Epilepsia2015 Mar;56(3):439-49. doi: 10.1111/epi.12923.
- This article made the cover of the March 2015 issue of Epilepsia.
- This article is highlighted in Nature Reviews Neurology 11, 125 (published online 24 February 2015) http://www.nature.com/nrneurol/journal/vaop/ncurrent/full/nrneurol.2015.22.html
- Boussadia B, Ghosh C, Plaud C, Pascussi JM, de Bock F, Rousset MC, Janigro D, Marchi N. Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression. Neuroscience 2014 Dec 5;281:124-34. doi: 10.1016/j.neuroscience.2014.09.055.
- Ghosh C, Hossain M, Puvenna V, Martinez-Gonzalez J, Alexopolous A, Janigro D, Marchi N. Expression and functional relevance of UGT1A4 in a cohort of human drug-resistant epileptic brains. Epilepsia 2013 Sep;54(9):1562-70. doi: 10.1111/epi.12318.
- Marchi N, Granata T, Ghosh C, Janigro D. Blood-brain barrier dysfunction and epilepsy: pathophysiologic role and therapeutic approaches. Epilepsia 2012 Nov;53(11):1877-86. doi: 10.1111/j.1528-1167.2012.03637.x.
- Ghosh C, Marchi N, Hossain M, Rasmussen P, Alexopoulos AV, Gonzalez-Martinez J, Yang H, Janigro D. A pro-convulsive carbamazepine metabolite: quinolinic acid in drug resistant epileptic human brain. Neurobiol Dis 2012 Jun;46(3):692-700. doi: 10.1016/j.nbd.2012.03.010.
- Ghosh C, Puvenna V, Gonzalez-Martinez J, Janigro D, Marchi N. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: a synergistic role in neurological diseases. Curr Drug Metab 2011 Oct;12(8):742-9.
- Ghosh C, Marchi N, Desai NK, Puvenna V, Hossain M, Gonzalez-Martinez J, Alexopoulos AV, Janigro D. Cellular localization and functional significance of CYP3A4 in the human epileptic brain. Epilepsia 2011 Mar;52(3):562-71. doi: 10.1111/j.1528-1167.2010.02956.x.
- Ghosh C, Gonzalez-Martinez J, Hossain M, Cucullo L, Fazio V, Janigro D, Marchi N. Pattern of P450 expression at the human blood-brain barrier: roles of epileptic condition and laminar flow. Epilepsia 2010 Aug;51(8):1408-17. doi: 10.1111/j.1528-1167.2009.02428.x.
Complete List of Publications in PubMed (*Note: under “Sinha C” and “Ghosh C”): PubMed