Chaitali  Ghosh,  Ph.D.

Chaitali Ghosh, Ph.D.

Staff Scientist

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195

 

Our laboratory conducts neurovascular research to better understand brain physiology and function in neurological disorders (e.g., epilepsy and epilepsy with other comorbidities such as stroke or depression), with a focus on the blood-brain barrier.

We investigate the mechanisms and pathophysiological alterations that could contribute to disease progression and/or 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. We also investigate the consequence of metabolic disturbances at the blood-brain barrier in epilepsy and other neurological disorders and its impact on the neurons.

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 study the neurovascular properties ex vivo and in vitro using a humanized dynamic neurovascular unit established with primary brain cells isolated from resected brain tissues post-epilepsy surgery, and in vivo by using rodent models of seizure/epilepsy.

The long-term goal of these studies is to develop a screening platform for pharmacological compounds, including drugs, across the blood-brain barrier. We also strive to identify novel therapeutic targets and potential biomarkers in the brain and vasculature for improving drug efficacy.

Lay Summary

Our laboratory investigates the role of the blood-brain barrier (a type of cell “shield” that prevents harmful substances from crossing into the brain) in health and disease. Our goals are to improve drug therapy and minimize harmful side effects caused by drug interactions.


View publications by Chaitali Ghosh, PhD. PubMed

Selected publications: 

Ghosh, C., Westcott R., Perucca E., Hossain M., Bingaman W., Najm IM. Cytochrome P450-mediated antiseizure medication interactions influence apoptosis, modulate the brain BAX/Bcl-XL ratio and aggravate mitochondrial stressors in human pharmacoresistant epilepsy. Front. Pharmacol. 2022 doi: 10.3389/fphar.2022.983233.

Westcott R., Chung N., Ghosh A., Ferguson L., Bingaman W., Najm IM., Ghosh, C. Glucocorticoid Receptor beta Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication. Int J Mol Sci. 2022. 23(9). doi: 10.3390/ijms23094940. PMID: 35563330; PMCID: PMC9099578.

Ghosh, C., Myers R., O’Connor C, Williams S, Liu X, Hossain M, Nemeth M, Najm, IM. Cortical dysplasia in rats provokes neurovascular alterations, GLUT1 dysfunction, and metabolic disturbances that are sustained post-seizure induction. Mol Neurobiol. 2022 Jan 27. doi: 10.1007/s12035-021-02624-2. Online ahead of print. PMID: 35084654.

Achar, A., Myers, R., Ghosh, C. Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy. Biomedicines. 2021 Dec 4, 9 (12): 1834. https://doi.org/10.3390/biomedicines9121834.

Achar A, Ghosh C. Multiple hurdle mechanism and blood-brain barrier in epilepsy: glucocorticoid receptor-heat shock proteins on drug regulation. Neural Regen Res. 2021 Dec;16(12):2427-2428. doi: 10.4103/1673-5374.313046.

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].

Rahman MT, Ghosh C, Hossain M, Linfield D, Rezaee F, Janigro D, Marchi N, van Boxel-Dezaire AHH. IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases. Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):274-279. doi: 10.1016/j.bbrc.2018.11.021. Epub 2018 Nov 16.

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].

Boussadia B, Lakhal L, Payrastre L, Ghosh C, Pascussi JM, Gangarossa G, Marchi N. Pregnane X Receptor Deletion Modifies Recognition Memory and Electroencephalographic Activity. Neuroscience. 2018 Feb 1;370:130-138. doi: 10.1016/j.neuroscience.2017.07.038. Epub 2017 Jul 23. PMID: 28743453 Free PMC article.

Runtz L, Girard B, Toussenot M, Espallergues J, Fayd'Herbe De Maudave A, Milman A, deBock F, Ghosh C, Guérineau NC, Pascussi JM, Bertaso F, Marchi N. Hepatic and hippocampal cytochrome P450 enzyme overexpression during spontaneous recurrent seizures. Epilepsia. 2018 Jan;59(1):123-134. doi: 10.1111/epi.13942. Epub 2017 Nov 10. PMID: 29125184 Free PMC article.

Banjara M, Ghosh C, Dadas A, Mazzone P, Janigro D. Detection of brain-directed autoantibodies in the serum of non-small cell lung cancer patients. PLoS One. 2017 Jul 26;12(7):e0181409. doi: 10.1371/journal.pone.0181409. eCollection 2017. PMID: 28746384 Free PMC article.

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.

Boussadia B, Gangarossa G, Mselli-Lakhal L, Rousset MC, de Bock F, Lassere F, Ghosh C, Pascussi JM, Janigro D, Marchi N. Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo. Exp Neurol. 2016 Sep;283(Pt A):39-48. doi: 10.1016/j.expneurol.2016.05.018. Epub 2016 May 27. PMID: 27240521 Free PMC article.

Puvenna V, Engeler M, Banjara M, Brennan C, Schreiber P, Dadas A, Bahrami A, Solanki J, Bandyopadhyay A, Morris JK, Bernick C, Ghosh C, Rapp E, Bazarian JJ, Janigro D. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy. Brain Res. 2016 Jan 1;1630:225-40. doi: 10.1016/j.brainres.2015.11.007. Epub 2015 Nov 7. PMID: 26556772 Free PMC article.

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

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. Epub 2014 Oct 2. PMID: 25280786 Free PMC article.

Bargerstock E, Puvenna V, Iffland P, Falcone T, Hossain M, Vetter S, Man S, Dickstein L, Marchi N, Ghosh C, Carvalho-Tavares J, Janigro D. Is peripheral immunity regulated by blood-brain barrier permeability changes? PLoS One. 2014 Jul 2;9(7):e101477. doi: 10.1371/journal.pone.0101477. eCollection 2014. PMID: 24988410 Free PMC article.

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.

Iffland PH 2nd, Carvalho-Tavares J, Trigunaite A, Man S, Rasmussen P, Alexopoulos A, Ghosh C, Jørgensen TN, Janigro D. Intracellular and circulating neuronal antinuclear antibodies in human epilepsy. Neurobiol Dis. 2013 Nov;59:206-19. doi: 10.1016/j.nbd.2013.07.006. Epub 2013 Jul 21. PMID: 23880401 Free PMC article

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. Epub 2013 Jul 19. PMID: 23865846 Free PMC article. 

Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D. Consequences of repeated blood-brain barrier disruption in football players. PLoS One. 2013;8(3):e56805. doi: 10.1371/journal.pone.0056805. Epub 2013 Mar 6. PMID: 23483891 Free PMC article. 

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. Epub 2012 Aug 20. PMID: 22905812 Free PMC article. Review.

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. Epub 2012 Mar 9. PMID: 22426401 Free PMC article.

Biddlestone-Thorpe L, Marchi N, Guo K, Ghosh C, Janigro D, Valerie K, Yang H.Nanomaterial-mediated CNS delivery of diagnostic and therapeutic agents. Adv Drug Deliv Rev. 2012 May 15;64(7):605-13. doi: 10.1016/j.addr.2011.11.014. Epub 2011 Dec 8. PMID: 22178615 Free PMC article. Review.

Marchi N, Johnson AJ, Puvenna V, Johnson HL, Tierney W, Ghosh C, Cucullo L, Fabene PF, Janigro D. Modulation of peripheral cytotoxic cells and ictogenesis in a model of seizures. Epilepsia. 2011 Sep;52(9):1627-34. doi: 10.1111/j.1528-1167.2011.03080.x. Epub 2011 May 31. PMID: 21627645 Free PMC article.

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. doi: 10.2174/138920011798357051. PMID: 21568937 Free PMC article. Review.

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. Epub 2011 Feb 5. PMID: 21294720 Free PMC article.

Marchi N, Teng Q, Ghosh C, Fan Q, Nguyen MT, Desai NK, Bawa H, Rasmussen P, Masaryk TK, Janigro D. Blood-brain barrier damage, but not parenchymal white blood cells, is a hallmark of seizure activity. Brain Res. 2010 Sep 24;1353:176-86. doi: 10.1016/j.brainres.2010.06.051. Epub 2010 Jun 27. PMID: 20599815 Free PMC article.

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. Epub 2010 Jan 13. PMID: 20074231 Free PMC article.

Granata T, Marchi N, Carlton E, Ghosh C, Gonzalez-Martinez J, Alexopoulos AV, Janigro D. Management of the patient with medically refractory epilepsy. Expert Rev Neurother. 2009 Dec;9(12):1791-802. doi: 10.1586/ern.09.114. PMID: 19951138 Free PMC article. Review.

Marchi N, Betto G, Fazio V, Fan Q, Ghosh C, Machado A, Janigro D. Blood-brain barrier damage and brain penetration of antiepileptic drugs: role of serum proteins and brain edema. Epilepsia. 2009 Apr;50(4):664-77. doi: 10.1111/j.1528-1167.2008.01989.x. Epub 2009 Jan 21. PMID: 19175391 Free PMC article.

Marchi N, Fan Q, Ghosh C, Fazio V, Bertolini F, Betto G, Batra A, Carlton E, Najm I, Granata T, Janigro D. Antagonism of peripheral inflammation reduces the severity of status epilepticus. Neurobiol Dis. 2009 Feb;33(2):171-81. doi: 10.1016/j.nbd.2008.10.002. Epub 2008 Oct 28. PMID: 19010416 Free PMC article.

Ghosh C, Storey-Workley M, Usip S, Hafemeister J, Miller KE, Papka RE. Glutamate and metabotropic glutamate receptors associated with innervation of the uterine cervix during pregnancy: receptor antagonism inhibits c-Fos expression in rat lumbosacral spinal cord at parturition.  J Neurosci Res. 2007 May 1;85(6):1318-35. doi: 10.1002/jnr.21225. PMID: 17304580

Sinha C, Seth K, Islam F, Chaturvedi RK, Shukla S, Mathur N, Srivastava N, Agrawal AK. Behavioral and neurochemical effects induced by pyrethroid-based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period.  Neurotoxicol Teratol. 2006 Jul-Aug;28(4):472-81. doi: 10.1016/j.ntt.2006.03.005. Epub 2006 Jul 13. PMID: 16842967

Chaturvedi RK, Shukla S, Seth K, Chauhan S, Sinha C, Shukla Y, Agrawal AK. Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease. Neurobiol Dis. 2006 May;22(2):421-34. doi: 10.1016/j.nbd.2005.12.008. Epub 2006 Feb 9. PMID: 16480889

Shukla S, Agrawal AK, Chaturvedi RK, Seth K, Srivastava N, Sinha C, Shukla Y, Khanna VK, Seth PK. Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's disease. J Neurochem. 2004 Oct;91(2):274-84. doi: 10.1111/j.1471-4159.2004.02715.x. PMID: 15447661.

Sinha C, Agrawal AK, Islam F, Seth K, Chaturvedi RK, Shukla S, Seth PK. Mosquito repellent (pyrethroid-based) induced dysfunction of blood-brain barrier permeability in developing brain. Int J Dev Neurosci. 2004 Feb;22(1):31-7. doi: 10.1016/j.ijdevneu.2003.10.005. PMID: 15013076

Sinha C, Shukla GS. Species variation in pesticide-induced blood-brain barrier dysfunction. Hum Exp Toxicol. 2003 Dec;22(12):647-52. doi: 10.1191/0960327103ht405oa. PMID: 14992326

Chaturvedi RK, Agrawal AK, Seth K, Shukla S, Chauhan S, Shukla Y, Sinha C, Seth PK. Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation with fetal ventral mesencephalic cells (VMC) on functional restoration in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease: neurobehavioral, neurochemical and immunohistochemical studies. Int J Dev Neurosci. 2003 Nov;21(7):391-400. doi: 10.1016/s0736-5748(03)00087-x. PMID: 14599485

 Complete List of Publications in PubMed (*Note: under “Sinha C” and “Ghosh C”): 

PubMed


12/08/2020 |  

COVID-19 May Also Invade the Central Nervous System, Cause Neurological Illnesses

In a new review, Dr. Ghosh notes that recent case reports of COVID-19-associated neurological disorders, which may result from blood-brain barrier dysfunction, demonstrate the virus’ neuroinvasive potential.




11/04/2020 |  

Potential Target Discovered for Reversing Drug Resistance in Epilepsy

Dr. Ghosh’s team has learned about an important relationship between the glucocorticoid receptor and heat shock proteins, which may have clinical implications for treating patients who have drug-resistant epilepsy.