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 or 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), drug 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 and understand the mechanism involved. For this, we use a humanized dynamic in vitro neurovascular unit, established with primary brain cells isolated from resected human brain tissues post-epilepsy surgery. We simultaneously compare drug metabolite levels in the blood and in the human brain tissue by in situ/ex vivo approaches and in vivo using rodent models of the disease. 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. We also strive to identify novel therapeutic targets in the brain and vasculature for improving drug efficacy. FUNDING: We thank the National Institutes of Health for its support of these projects and other foundation grants.
In other words ...
Our laboratory investigates the role of the blood-brain barrier in health and disease.
Achar A, Ghosh, C. COVID-19-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Relevance. Cells. 2020 Oct 27;9(11):2360. doi: 10.3390/cells9112360.
Hossain M., Williams S., Ferguson L., Bingaman W., Ghosh A., Najm IM., Ghosh, C. Heat Shock Proteins Accelerate the Maturation of Brain Endothelial Cell Glucocorticoid Receptor in Focal Human Drug-Resistant Epilepsy. Mol Neurobiol. 2020 Aug 3. doi: 10.1007/s12035-020-02043-9.
- Williams, S, Ghosh, C. Neurovascular glucocorticoid receptors and glucocorticoids: implications in health, neurological disorders and drug therapy. Drug Discov Today 2019 Sep 18. pii: S1359-6446(19)30353-8. doi: 10.1016/j.drudis.2019.09.009. [Epub ahead of print]
- Williams, S, Hossain M, Fergusan L, Busch RM, Marchi N, Gonzalez-Martinez J, Perucca E, Najm IM, Ghosh, C. Neurovascular Drug Biotransformation Machinery in Focal Human Epilepsies: Brain CYP3A4 Correlates with Seizure Frequency and Antiepileptic Drug Therapy. Mol Neurobiol. 2019 Dec; 56(12):8392-8407. doi: 10.1007/s12035-019-01673-y.
- Ghosh, C., Hossain M., Mishra S., Sameena K., Gonzalez-Martinez J., Marchi N., Janigro D., Bingaman W., Najm I . Modulation of glucocorticoid receptor in human epileptic endothelial cells impacts drug biotransformation in an in vitro blood‐brain barrier model. Epilepsia. 2018 28. doi: 10.1111/epi.14567. [Epub ahead of print].
- Williams, S., Hossain M., Mishra S., Gonzalez-Martinez J., Najm I., Ghosh, C. Expression and Functional Relevance of Death-Associated Protein Kinase in Human Drug-Resistant Epileptic Brain: Focusing on the Neurovascular Interface. Mol Neurobiol. 2018 Nov 9. doi: 10.1007/s12035-018-1415-z. [Epub ahead of print].
- Ghosh, C., Hossain M., Solanki J., Najm I., 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 Apr;58(4):576-585. doi: 10.1111/epi.13703. Epub 2017 Feb 15. PMID: 28199000.
- 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. Epilepsia 2015 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
Complete List of Publications in PubMed (*Note: under “Sinha C” and “Ghosh C”): PubMed
COVID-19 is known primarily as a respiratory disease, with symptoms that include cough, shortness of breath, and, in severe cases, acute respiratory distress syndrome and pneumonia. Now, researchers from the Department of Biomedical Engineering note in a recent review that infection with the coronavirus may also affect the central nervous system and cause corresponding neurological disorders, including ischemic stroke, encephalitis, encephalopathy and epileptic seizures.
Drug treatment is usually successful in controlling epilepsy. However, a significant percentage of patients—up to one-third of adults and one-quarter of children, according to the International League Against Epilepsy and the Epilepsy Foundation—have epilepsy that is drug-resistant, or pharmacoresistant. Specifically, this means that patients continue to experience seizures despite taking medications.
Glucocorticoid receptors (GRs) play a significant role in pharmacoresistant epilepsy and represent a potential therapeutic target, suggests an ongoing line of investigation by Cleveland Clinic researchers.