B.S., Cellular and Molecular Biology, San Diego State University, 2009
Ph.D., Cellular and Molecular Biology, University of California San Diego / San Diego State University, 2015
Postdoctoral training, Chemical and Biological Engineering, University of Wisconsin
Postdoctoral training, Institute for Hygiene and Microbiology, University of Würzburg
My research interests revolve around the host-pathogen interaction between bacterial pathogens and the human blood-brain barrier. Specifically how the blood-brain barrier fails to protect the brain during disease.
The human brain is an extremely demanding organ in the body. While only representing about 2% of the total body mass, it requires up to 20% of the total nutrients and oxygen. The primary role of the capillaries in the brain is to serve the brain’s needs by transporting beneficial substrates into the brain while restricting potentially harmful compounds and pathogens. Collectively the endothelial cells that comprise the lining of these brain capillaries are called the blood-brain barrier (BBB). The highly specialized brain endothelial cells (BECs) possess unique characteristics that greatly differ from blood vessels of peripheral tissues. These BECs cooperate in a number of ways to promote proper central nervous system homeostasis and brain function. However in many disease states the BBB is compromised leading to a number of complications and neuropathologies. Using human induced pluripotent (iPSC) stem cell technologies, we are able to derive BECs from iPSC sources that better mimic BBB phenotypes when compared to many other in vitro models. This allows us to interrogate the host-pathogen interaction with the BBB and examine barrier function and physiology during infection with meningeal pathogens.
Bacterial meningitis is a serious infection of the CNS that occurs when bacteria are able to gain access to the CNS by crossing or disrupting the BBB. When left untreated, bacterial meningitis is a uniformly fatal disease. Modern medical interventions have transformed bacterial meningitis into an often curable condition, however many survivors may still experience long lasting neurological problems such as deafness, blindness, seizures, and others. My research focuses primarily on the clinically relevant meningeal pathogens Streptococcus agalactiae (Group B Streptococcus, GBS), and Neisseria meningitidis (meningococcus, Nm) and how they are able to subvert the BBB’s defenses and gain access to the CNS.
Endres LM, Schubert-Unkmeir A, Kim BJ*. Neisseria meningitidis infection of induced pluripotent stem-cell derived brain endothelial cells. Journal of Visualized Experiments. July 2020.
Kim BJ*, McDonagh MA, Deng L, Gastfriend BD, Schubert-Unkmeir A, Doran KS, Shusta EV. Streptococcus agalactiae disrupts P-glycoprotein function in brain endothelial cells. Fluids and Barriers of the CNS. August 2019.
Kim BJ, Shusta EV, Doran KS. Current perspectives in modeling bacteria and blood-brain barrier interactions. Frontiers in Microbiology. June 2019.
Gomes S, Westermann A, Sauerwein T, Hertlein T, Ohlsen K, Shusta EV,
Metzger M, Appelt-Menzel A*, Schubert-Unkmeir A*, Kim BJ*. Interaction of Neisseria meningitidis with induced pluripotent stem cell derived brain endothelial cells. Frontiers in Microbiology. May 2019.
Kim BJ, Schubert-Unkmeir A. In vitro models for studying the interaction of Neisseria meningitidis with human brain endothelial cells. Methods in Molecular Biology. March 2019.
Pate KM, Kim BJ, Shusta EV, Murphy RM. Transthyretin mimetics as anti-beta- amyloid agents: A comparison of peptide and protein approaches. ChemMedChem. April 2018.
Kim BJ, Bee OB, McDonagh MA, Stebbins MJ, Palecek SP, Doran KS, Shusta EV. Modeling Group B Streptococcus – blood-brain barrier interaction using iPSC-derived brain endothelial cell. mSphere. November 2017.
Doran KS, Fulde M, Gratz N, Kim BJ, Nau R, Prasadaro N, Schubert-Unkmeir A, Tuomanen E, Valentin-Weigand P. Host-Pathogen interactions in bacterial meningitis. Acta Neuropathologica. January 2016.
Sin J, Andres AM, Taylor DJ, Weston T, Hiraumi, Stotland A, Kim BJ, Huang C, Doran KS, Gottlieb RA. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy. November 2015.
Kim BJ, Hancock B, Reyes E, Bermudez A, DelCid N, van Sorge N, Lauth X, Hilton B, Stotland A, Banarjee A, Buchanan J, Traver D, Wolkowicz R, Doran KS. Bacterial Induction of Snail1 Contributes to Blood-Brain Barrier Disruption. Journal of Clinical Investigation. May 2015.
Kim BJ, Hancock B, Del Cid N, Traver D, Doran KS. Streptococcus agalactiae infection in zebrafish larvae. Microbial Pathogenesis. January 2015.
Mu R, Kim BJ, Paco C, Del Rosario Y, Courtney HS, Doran KS. Identification of a Group B Streptococcal fibronectin binding protein, SfbA, that contributes to invasion of brain endothelium and the development of meningitis. Infect Immun. March 2014.
Krishnan V, Dwivedi P, Kim BJ, Samal A, Macon K, Ma X, Mishra A, Doran KS, Ton-That H, Narayana SV. Structure of Streptococcus aglactiae tip pilin GBS104:
a model for GBS pili assembly and host interactions. Acta Crystallogr D. May 2013.
Seo H, Mu R, Kim BJ, Doran KS, Sullam P. Binding of the Serine Rich Repeat Glycoprotein Srr1 of Streptococcus agalactiae to Fibrinogen Promotes Attachment to Brain Endothelium and the Development of Meningitis. PLoS Pathogens. October 2012.
Banarjee A, Kim BJ, Carmona E, Gurney M, Carlos C, Prasadarao N, Doran KS. Bacterial Pili Exploit Integrin Machinery to Promote Immune Activation and Efficient Blood-Brain Barrier Penetration. Nature Comm. September 2011.
Elio Schaechter’s Microbiology Blog: American Society for Microbiology’s Small Things Considered. Kim BJ and Sin J. Pneumococcus: Nature’s Tiniest Cheat. (2011). http://schaechter.asmblog.org/schaechter/2011/04/pneumococcus-natures-tiniest-cheat.html