Bioprocessing and Biotechnology, Neurobiology/Neuropharmacology, Therapy Discovery and Development
Dr. Sumbria, who joined KGI in July 2014, received her PhD in Pharmaceutical Sciences from the Texas Tech University Health Sciences Center (TTUHSC) in 2010. At TTUHSC, her research centered on the development of intracerebral microdialysis as an experimental tool to study changes in the blood-brain barrier (BBB) permeability in ischemic stroke.
Dr. Sumbria completed her postdoctoral training at the Department of Medicine, blood-brain barrier laboratory at the University of California, Los Angeles and the Department of Neurology at the University of California, Irvine from 2011-2014. During her postdoctoral research at UCLA, Dr. Sumbria focused on the problem of the BBB bottleneck in CNS drug delivery. Particularly, her research focused on the use of receptor-mediated transcytosis for non-invasive delivery of biologics and other large molecular weight therapeutics across the BBB, and studying their pharmacologic effects in different experimental models of CNS disorders. At UCI, the focus of her research was studying the role of cerebral microbleeds in cerebrovascular diseases like stroke.
Besides research, Dr. Sumbria has been extensively involved in teaching and mentoring laboratory research personnel’s and graduate students. Dr. Sumbria received her Ph.D. in Pharmaceutical Sciences from the School of Pharmacy at Texas Tech University Health Sciences Center in Amarillo, Texas and a Bachelor of Technology (B.Tech) in Pharmaceuticals & Fine Chemicals from the Institute of Chemical Technology in Mumbai, India.
Michael M, Grigoryan M, Kilday K, Sumbria RK, Vasilevko V, Ryn J, Cribbs D, Paganini-Hill A, Fisher M. Effects of Dabigatran in Mouse Models of Aging and Cerebral Amyloid Angiopathy. Front Neurol. 2019. (Just Accepted)
Sun J, Boado R, Pardridge W, Sumbria RK. Plasma pharmacokinetics of high-affinity transferrin receptor antibody-erythropoietin fusion protein is a function of effector attenuation in mice. Mol Pharm. 2019 Aug 5;16(8):3534-3543.
Sun J, Martin JM, Vanderpoel V, Sumbria RK. The Promises and Challenges of Erythropoietin for Treatment of Alzheimer’s Disease.Neuromolecular Med. 2019 Mar;21(1):12-24.
Chang R, Al Maghribi A, Vanderpoel V, Vasilevko V, Cribbs DH, Boado R, Pardridge WM, Sumbria RK. Brain Penetrating Bifunctional Erythropoietin-Transferrin Receptor Antibody Fusion Protein for Alzheimer’s Disease. Mol Pharm. 2018 Oct 9;PubMed PMID: 30252487.
Chang R, Castillo J, Zambon AC, Krasieva TB, Fisher MJ, Sumbria RK. Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds. Front Cell Neurosci. 2018;12:279. PubMed PMID: 30237761; PubMed Central PMCID: PMC6135875.
Chang R, Castillo J, Zambon AC, Krasieva T, Fisher MJ, Sumbria RK*. Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds. Front. Cell. Neurosci. 2018 Sep 6;12:279. doi: 10.3389/fncel.2018.00279. PubMed PMID: 30237761.
Sumbria RK, Grigoryan MM, Vasilevko V, Paganini-Hill A, Kilday K, Kim R, Cribbs DH, Fisher MJ. Aging exacerbates development of cerebral microbleeds in a mouse model. J Neuroinflammation. 2018 Mar 6;15(1):69. doi: 10.1186/s12974-018-1092-x. PubMed PMID: 29510725.
Chang R, Knox J, Chang J, Derbedrossian A, Vasilevko V, Cribbs D, Boado RJ, Pardridge WM, Sumbria RK*. Blood-Brain Barrier Penetrating Biologic TNF-α Inhibitor for Alzheimer’s Disease. Mol Pharm. 2017 Jul 3;14(7):2340-2349. Epub 2017 May 31. PubMed PMID: 28514851.
Sumbria RK, Vasilevko V, Grigoryan MM, Paganini-Hill A, Kim R, Cribbs DH, Fisher MJ. Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages. J Neuroinflammation. 2017 Jun 5;14(1):114. PubMed PMID: 28583195; PubMed Central PMCID: PMC5460510.
Chang R, Yee KL, Sumbria RK*. Tumor necrosis factor α Inhibition for Alzheimer’s Disease. J Cent Nerv Syst Dis. 2017 May 15;9:1179573517709278. eCollection 2017. Review. PubMed PMID: 28579870; PubMed Central PMCID: PMC5436834.
Sumbria RK, Grigoryan MM, Vasilevko V, Krasieva TB, Scadeng M, Dvornikova AK, Paganini-Hill A, Kim R, Cribbs DH, Fisher MJ. A murine model of inflammation-induced cerebral microbleeds. J Neuroinflammation. 2016 Aug 30;13(1):218. PubMed PMID: 27577728; PubMed Central PMCID: PMC5006574.
Yang, F., Sumbria, R., Xue, D., Yu, C., He, D., Liu, S., Paganini-Hill, A., Fisher, M. (2014): Effects of PDE4 Pathway Inhibition in Rat Experimental Stroke. J. Pharm. Pharm. Sci., 2014;17(3):362-70.
Liu, S., Grigoryan, M., Vasilevko, V., Sumbria, R., Paganini-Hill, A., Cribbs, D., Fisher, M. (2014): Comparative Analysis of H&E and Prussian Blue Staining in a Mouse Model of Cerebral Microbleeds. J. Histochem. Cytochem., Epub ahead of print. PMID: 25063000.
Sumbria, R., Lu, J.Z., Hui, E.K.-W., Boado, R.J., Pardridge, W.M. (2013): Disaggregation of Amyloid Plaque in Brain of Alzheimer’s Disease Transgenic Mice with Daily Subcutaneous Administration of a Tetravalent Bi-Specific Antibody That Targets the Transferrin Receptor and the Abeta Amyloid Peptide. Mol Pharm., Epub ahead of print. PMID: 23924247.
Boado, R.J., Lu, J.Z., Hui, E.K.-W., Sumbria, R., Pardridge, W.M. (2013): Blood-Brain Barrier Molecular Trojan Horse Enables Brain Imaging of Radioiodinated Recombinant Protein in the Rhesus Monkey. Bioconjug. Chem., Epub ahead of print. PMID: 24059813.
Sumbria, R., Boado, R.J., Pardridge, W.M. (2013): Combination Stroke Therapy in the Mouse with Blood-Brain Barrier Penetrating IgG-GDNF and IgG-TNF Decoy Receptor Fusion Proteins. Brain Res., Epub ahead of print. PMID: 23428543.
Sumbria, R., Zhou, Q.-H., Lu, J.Z., Hui, E.K.-W., Boado, R.J., Pardridge, W.M. (2013): Pharmacokinetics and Brain Uptake of an IgG-TNF Decoy Receptor Fusion Protein Following Intravenous, Intraperitoneal and Subcutaneous Administration in the Mouse.Mol Pharm., Epub ahead of print. PMID: 23410508.
Boado, R.J., Lu, J.Z., Hui, E.K.-W., Sumbria, R., Pardridge, W.M. (2012): Pharmacokinetics and Brain Uptake in the Rhesus Monkey of Fusion Protein of Arylsulfatase A and a Monoclonal Antibody Against the Human Insulin Receptor. Biotechnol Bioeng., Epub ahead of print. PMID: 23192358.
Sumbria, R., Boado, R.J., Pardridge, W.M. (2012): Brain Protection from Stroke with Intravenous TNFα Decoy Receptor-Trojan Horse Fusion Protein. J. Cereb. Blood Flow Metab., 32(10):1933-8. PMID: 22714051.
Sumbria, R., Boado, R.J., Pardridge, W.M. (2012): Imaging Amyloid Plaque in Alzheimer’s Disease Brain with a Biotinylated Aβ Peptide Radiopharmaceutical Conjugated to an IgG-Avidin Fusion Protein.Bioconjug. Chem., Epub ahead of print. PMID: 22624578.
Mdzinarishvili, A., Sumbria, R., Lang, D., Klein,J. (2012): Ginkgo Extract Egb761 Confers Neuroprotection by Reduction of Glutamate Release in Ischemic Brain. J. Pharm. Pharm. Sci.,15(1):94-102. PMID: 22365091.
Lang, D., Kiewert, C., Mdzinarishvili, A., Schwarzkopf. T.M., Sumbria, R., Hartmann, J., Klein, J. (2011): Bilobalide, a Neuroprotectant that Reduces Ischemia-Induced Glutamate Release In Vivo. Brain Res., 1425:155-63. PMID: 22032877.
Zhou, Q.-H., Sumbria, R., Hui, E.K.-W., Lu, J.Z., Boado, R.J., and Pardridge, W.M. (2011): Neuroprotection with a Brain-Penetrating Biologic Tumor Necrosis Factor Inhibitor. J. Pharmacol. Exp. Ther., 339: 618-623. PMID: 21831964.
BBB alterations and cerebral microbleeds development: Cerebral microbleeds are microscopic hemorrhages that are formed by blood product extravasation from the cerebral blood vessels into the brain parenchyma. Cerebral microbleeds increase with age and are prevalent with conditions like stroke, Alzheimer disease, cerebral amyloid angiopathy. The underlying mechanisms involved in the development of cerebral microbleeds are not clear. Dr. Sumbria’s research efforts are directed towards elucidating the mechanisms involved in erythrocyte extravasation across the brain endothelium.
CNS drug delivery: Due the extremely restrictive nature of the BBB, brain delivery of majority of drugs (about 98% of small molecules and 100% of large molecules do not cross the BBB) has been a big challenge. Dr. Sumbria’s research focuses on non-invasive drug delivery approaches for solving the brain drug delivery problem for CNS pathology. She is specifically interested in the delivery of biologics and other large molecular weight therapeutics into the brain and studying their potential, either as imaging or therapeutic agents, in experimental models of CNS disease.
NIRG-15-361188, Alzheimer’s Association
A brain-penetrating biologic TNF-alpha inhibitor for Alzheimer’s disease: The overall goal of the project was to investigate the protective effects of a brain-penetrating biologic TNF-alpha inhibitor in a mouse model of Alzheimer’s disease.
30082449, Joseph H. Stahlberg Foundation
Brain penetrating erythropoietin for Alzheimer’s disease
This funding provided support for a pilot study to investigate the effect of a brain-penetrating erythropoietin compared with vehicle treatment, in a male transgenic mouse model of Alzheimer’s disease.
1R21AG055949-01, National Institute of Aging/National Institute of Health
Re-engineering Erythropoietin for Alzheimer’s Disease: The overall goal of the project is to investigate the effect of a neuroprotective and neuroregenerative approach for Alzheimer’s disease. The model neurotrophin studied is a brain-penetrating analog of EPO in a mouse model of Alzheimer’s disease.
R01NS020989, National Institute of Neurological Disorders and Stroke/National Institute of Health
Role: Co-I, PI: Mark Fisher/David Cribbs
Hemorheological Factors in Cerebral Ischemia: Overall aim of this project is to investigate the role of brain endothelial erythrophagocytosis in cerebral microbleed development.
Joseph H. Stahlberg Foundation
Optimizing the Dosing of a Novel Brain Penetrating Erythropoietin Analog for Alzheimer’s Disease
R01AG062840, National Institute of Aging/National Institute of Health
A Brain Penetrating Bi-functional Transferrin Receptor Antibody-TNF-alpha Decoy Receptor Fusion Protein for Alzheimer’s Disease