Prof. Kavi Devraj

Associate Professor
Department of Biological Sciences

AD, BBB Targeted Therapeutics, CNS Diseases (Stroke, CNS Drug Delivery, Cancers), Infections, Microfluidic Devices, Neuroscience and Biomedical Engineering - Blood-Brain Barrier (BBB), Neurovascular Unit (NVU), Transport Mechanisms and Kinetics

University Education

1996-2000 Bachelors: Chemical Engineering, National Institute of Technology (NITW), Warangal, India

2000-2002 Masters: Biomedical Engineering, Worcester Polytechnic Inst. (WPI), Worcester, MA, USA

2006-2008 Graduate School Teaching Certificate: Integrative Biosciences, Penn State University, Hershey, PA, USA (accepted by “Arbeitsstelle Medizindidaktik” of the Goethe University Hospital in February 2018 for ‘Habilitation’ requirements)

2002-2009 PhD: Integrative Biosciences, Neural & Behavioral Sciences, Penn State University, Hershey, PA, USA

Professional Career

2001-2002 Teaching Assistant, Biomedical Engg., Worcester Polytechnic Institute WPI, USA

2001-2001 Summer Intern, Genzyme Inc. (Sanofi), Framingham, MA, USA

2002-2002 ADA Summer Intern, Neural & Behavioral Sciences, Penn State Univ, PA, USA

2003-2003 COSAT Summer Fellow, Neutrogena (Johnson & Johnson company), LA, USA

2004-2009 Research Assistant, Neural & Behavioral Sciences, Penn State University, PA, USA

2006-2007 Graduate Lecturer: Penn State University, Hershey, PA, USA

2010-2015 Postdoctoral Fellow, Institute of Neurology, Goethe University, Frankfurt, Germany

2015-2018 Group Leader, Pharmazentrum & Edinger Institute, Goethe University, Frankfurt, Germany

2019-2023 Group Leader (Associate Professor), Edinger Institute, Goethe University, Germany

2023-current Associate Professor, BITS-Pilani, Hyderabad, India

Research Interests

The Blood-Brain Barrier transport dynamics (BBTΔ) group is interested in mechanisms, kinetics, and their regulation in the transport of molecules and pathogens across the blood-brain barrier (BBB) in the homeostasis of the central nervous system (CNS) and pathologies such as AD, stroke, meningitis, EAE (MS), epilepsy, brain cancers, and brain infections.

The blood-brain barrier (BBB) formed by brain microvascular endothelial cells maintains CNS homeostasis with its function regulated by pericytes, astrocytes, and microglia, which together form the neurovascular unit (NVU). Several CNS diseases such as stroke, AD, multiple sclerosis, epilepsy, brain cancers, and brain infections are associated with BBB dysfunction. In diseases not associated with BBB dysfunction, drug delivery to the brain is challenging due to the BBB. Our focus is on understanding the mechanisms and the role of BBB/NVU dysfunction in the pathology of these neurological diseases.

Our long-term goal is to identify novel vascular therapeutic targets in CNS diseases associated with an impaired BBB and to identify novel and efficient targets at the NVU to modulate BBB permeability for drug delivery to the CNS. To realize these goals, our research will comprise state-of-the-art techniques and interdisciplinary approaches described below and in a collaborative manner.

The Blood-Brain Barrier (BBB) and the Neurovascular Unit (NVU)

Research Objectives and Past Work

Our previous work could demonstrate the significance of S1P4 a sphingolipid receptor as a novel therapeutic target for altering BBB permeability (J Neuroscience, 2021).

Recently, we contributed (Science 2022) to the first major work in the BBB field that translates the molecular knowledge of Wnt signalling at the BBB to engineer therapeutic molecules for major CNS diseases. Other previous works in the BBB field include targeting HIF-1a at the BBB in meningitis (Acta Neuropathologica, 2020), and targeting neurovasculature in diabetic retinopathy (Nature, 2017).

Our current/proposed work is on targeting NVU as a whole for BBB dysfunction in CNS disease for which we recently developed a method EPAM-ia, a flow cytometry-based method that we successfully applied to a preclinical stroke model and human brain tissue (Acta Neurolopathologica 2022, Nature Protocols 2023).

Approaches/techniques

Approaches include transwell culture employing NVU cells (EC, AC, PC, & MG) in vitro and microvessels and FACS-isolated NVU cells ex vivo from experimental/transgenic animal models and human biopsy/autopsy material. In vivo approaches include fluorescent tracer permeability analyses.

Histochemistry followed by confocal/super-resolution/ or electron microscopy is applied for localization/expression analysis in all the above approaches. TEER/fluorescent dextran permeability assays are utilized for in vitro analyses.

Transcriptomic, proteomic, & bioinformatics analyses are utilized for the investigation of molecular mechanisms underlying neurological diseases affecting BBB utilizing the above in vitro and ex vivo samples. Western blotting, qRT-PCR, and immuno-fluorescence are routinely used for validation and translational analyses.

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