Associate Professor
Jacobs School of Medicine & Biomedical Sciences
Apoptosis and cell death; Bioinformatics; Endocrinology; Gene Expression; Gene Therapy; Genomics and proteomics; Immunology; Molecular and Cellular Biology; Molecular Basis of Disease; Neurobiology; RNA; Viral Pathogenesis
Dr. Mahajan has established herself as an investigator in the area of neuropathogenesis of HIV-1 in the context of drug abuse. Her research is focused on examining role of neuroinflammation in neurodegenerative disorders. Microglia-mediated neuroinflammation is a pathological hallmark of neurodegenerative diseases and neurological damage and her research examines the integrative role played by microglia in the maintenance of nervous system homeostasis and progression of neurological disease pathogenesis.
She has established 2D and 3D Blood Brain Barrier (BBB) models, that allow studying mechanisms of BBB pathophysiology, examine BBB integrity and evaluate permeability of neurotherapeutics across the BBB.
She investigates the role of a unique key signaling molecule in the dopaminergic pathway called DARPP-32, that impacts drug addiction, depression and other neurological disorders.
Dr. Mahajan beleives in collaborative, interdisciplinary partnerships and has established a long standing collaborative research program between various Departments within UB that include the Institute of Lasers, Photonics and Biophotonics, Research Institute of Addiction, Department of Chemical and Biological Engineering; Dept of Pharmaceutical Sciences; Department of Oral Biology and Department of Biomedical Informatics; and also multi-institutional collaborations with University of Rochester Medical Center and SUNY Albany and SUNY Global Health Institute. This inclusive strategy has facilitated the emergence of a robust, innovative clinical translational research program that continues to grow steadily.
Dr Mahajan has obtained independent research funding from NIDA, NSF iCorp, Pharmaceuticals like Pfizer, Shire, Global- CRDF, US- Fulbright and other Private Foundations such as Dr. Louis Skalrow Memorial trust.
Dr. Mahajan is Director of Research of the Division of Allergy, Immunology & Rheumatology. She supervises the research training of the Allergy fellows, Medical residents, graduate and undergraduate students from many basic and allied science departments within UB.
Dr. Mahajan has presented her research work at National and International conferences and was an invited speaker at several seminars and colloquiums. She has authored over 150 publications in several mid-high impact peer reviewed journals and has thus demonstrated a high level of scholarly productivity. She is a reviewer and an adhoc member of the editorial board of several journals in her field and serves as a review panel member for NIH and NSF study sections.
The following is a brief synopsis of her research interests.
HIV neuropathogenesis in the context of drug abuse:
Opiates act as co-factors in the pathogenesis of HIV-1 infections and exacerbation of HIV associated neurological disorders (HAND) are observed with opiate abuse. Opiate abuse by HIV-1 infected subjects may exacerbate the progression of HAND as a consequence of the combined effects of HIV-1 induced neurotoxins plus opiate induced increases in the dopaminergic signalling activation. In this context, her research is focused on the DARPP-32 signalling pathway. Addictive drugs act on the dopaminergic system of the brain and perturb the function of the dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32 kD (DARPP-32). DARPP-32 is critical to the pathogenesis of drug addiction by modulating both transcriptional and post-translational events in different regions of the brain.
BBB Research:
The blood-brain barrier is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of molecules between the blood stream and the brain parenchyma. The 2D and 3D in-vitro BBB models developed and validated in Dr. Mahajan 's lab allow examining effects of drugs of abuse on BBB permeability, mechanisms of BBB transport, and tight junction modulation. Our goal remains to determine the impact of current and potential CNS antiretrovirals, psychopharmacologic, and other Nanotherapeutics on the integrity of the BBB in HIV associated neurological disorder and other neurodegenerative disease model systems. Additionally, she also investigate mechanisms that underlie drug-of-abuse-induced neuronal apoptosis/ pyroptosis.
Systems biology:
Genomic / Proteomic/ Metabolomic studies to help identify key genes/ proteins/ metabolites that underlie disease states, such as drug addiction, HIV disease progression, HAE, and other neurological disorders .
She has expanded her research program to include microbiome analyses and incorporated the utility of the computational drug discovery platform (CANDO) model that allows studying interaction between protein structures from microbiome genomes and determine the interactions that occur between them and other small molecules (drugs and human/bacterial metabolites). Using the CANDO Platform enables analysis of hierarchical fragment-based docking with compounds/drugs and the microbiome proteins/proteomes to determine which drugs and metabolites will potentially work most efficaciously in patients.
Nanomedicine:
Dr. Mahajan has developed a strong program in nanomedicine in collaboration with ILPB and has initiated several interdisciplinary clinical translational research areas that include 1) Nanotechnology based delivery systems to examine antitretroviral transport across the BBB; 2) Nanotherapeutics using siRNA/Plasmid delivery to specific regions in the brain to target various genes of interest that result in the modulation of behavioral response which are then studied in animal models of addiction/chronic pain; 3) Biodistribution studies of various nanotherapeutic formulations using PET small animal imaging. Further research work is focused on exploring epigenetic mechanisms that underlie drug addiction and mechanisms that underlie oxidative stress in neurodegenerative diseases.
Raman analysis:
Utilizing label-free, multimodal Raman spectroscopy to study Methamphetamine/Fentanyl-induced cell death (apoptosis and pyroptosis) in human neuronal cells in real time.
• Raman spectroscopy combined with optical diffraction tomography microscopy based on transport-of-intensity imaging (TIE-ODT), allows quantification of mitochondria volume changes during apoptosis and pyroptosis in real time.
• Raman spectroscopy-based approach to quantitate amount of cytochrome C in METH-treated neurons and observe the dynamics of cytochrome C, and reveals the initiation of apoptosis before morphological changes in the apoptotic cell are apparent.determining analgesic effects of the CBD vapor and exploring the mechanism of inflammasome activation that underlie CBD vapor induced lung pathology and will help highlight the role of CBD vaping in the development of chronic lung inflammation.
Pathophysiological role in bacterial-induced modulation of the neuro-immune axis:
• Sustained dysbiotic chronic systemic inflammation of periodontitis may contribute to prolonged neuroinflammation, functional cognitive impairment and neurodegenerative dysfunction. We are examining oral bacteria mechanistically impact the BBB and NVU to contribute to cognitive disorders- specifically how periodontal pathogens such as Treponema species promote glial activation with BBB dysfunction, contributing to neuroinflammation and neurodegeneration.