Supriya D. Mahajan PhD

Supriya Mahajan

Supriya D. Mahajan
PhD

Research Associate Professor

Department of Medicine

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

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

Contact Information
6074 UB‘s CTRC
Buffalo Niagara Medical Campus
875Ellicott Street
Buffalo, NY 14203
Phone: (716) 888-4776
Fax: (716) 859-1417
smahajan@buffalo.edu



Professional Summary:

Dr. Mahajan has established herself as an investigator in the area of neuropathogenesis of HIV-1 in the context of drug abuse. She has initiated several new projects that investigate the role of a unique key signaling molecule in the dopaminergic pathway that impacts drug addiction, depression and other neurological disorders. Her focus has always been on collaborative, interdisciplinary partnerships between various Departments within UB that include the Institute of Lasers, Photonics and Biophotonics, Research Institute of Addiction, Dept of Computer Science and Engineering, Dept of Pharmaceutical sciences and the Department of Bioengineering. This inclusive strategy has facilitated the emergence of a robust, innovative clinical translational research program for our Division that continues to grow steadily. Dr Mahajan has obtained independent research funding from NIDA, the pharmaceutical Pfizer, US- Fulbright and other Private Foundations such as Dr. Louis Skalrow Memorial trust to conduct some of these research projects. 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. 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 95 publications in several top quality 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.
The following is a brief synopsis of her research interests.
HIV neuropathogenesis in the context of drug abuse: We proposed that Opiates act as co-factors in the pathogenesis of HIV-1 infections by directly suppressing immune functions of the host through interactions with mu-opioid receptors on lymphocytes. Exacerbation of HIV encephalopathy (HIVE) is observed with opiate abuse. The mechanisms underlying HIVE are currently undetermined however, they likely to include the generation of endogenous neurotoxins combined, perhaps synergistically, with bioreactive HIV-1 envelope proteins. We believe that these proposed mechanisms may work through a common signal transduction mechanism activating dopamine D1 receptors in the nucleus accumbens of the brain. Opiate abuse by HIV-1 infected subjects may exacerbate the progression of HIVE as a consequence of the combined effects of HIV-1 induced neurotoxins plus opiate induced increases in the D1 receptor activation. We hypothesize that the dopaminergic signaling pathway is the central molecular mechanism that integrates the neuropathogenic activities of both HIV-1 infections and the abuse of opiate drugs. In this context our investigation 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. DARPP-32 is localized within neurons containing dopamine receptors and is a potent inhibitor of another key molecule in the dopaminergic signaling pathway, protein phosphatase 1 (PP-1). We propose that the sustained silencing of DARPP-32 gene expression using specific siRNA delivered to the brain is an innovative approach for the treatment of drug addiction. The specific challenge of the proposed project is the non-invasive delivery of biologically stable, therapeutic siRNA molecules to target cells within the brain. We are developing biocompatible nanoparticles to both protect DARPP-32 specific siRNA against degradation and deliver it from the systemic circulation across the BBB to specific dopaminergic neurons in the brain of patients with opiate addictions.
BBB Research:
While examining neuropathogenesis of HIV, we became interested in the role of the blood-brain barrier (BBB) in HIV neuropathogenesis with the objective of developing therapeutic interventions to prevent and limit the progression of HIV associated neurological disease. 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. We evaluated and validated both the 2 and 3 dimensional human in-vitro BBB models in my laboratory, that allowed examining permeability of virus, 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 medications on the integrity of the BBB in HIV associated neurological disorder and other neurodegenerative diseases. Additionally, We also investigate mechanisms that underlie drugs of abuse induced neuronal apoptosis.
Systems biology approach:
We expanded our investigation to include functional genomic/proteomic analyses that allowed characterization of gene/ protein modulation in response to a drug stimulus or under a specific disease condition. We developed an expertise in these large-scale genomic and proteomic studies and the genomic studies helped identify key genes that underlie molecular mechanisms in drug addiction, HIV diseases progression, and allowed examination of the interplay of genes and environmental factors. The proteomic studies confirmed the presence of specific proteins that regulate key biological processes in drug addiction and HIV diseases progression. Recently, We have expanded my 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 small molecules (drugs and human/bacterial metabolites that are already a part of or continue to be added to the CANDO library. Using the CANDO Platform we are able to do the hierarchical fragment-based docking with dynamics between those compounds/drugs and the microbiome proteins/proteomes to determine which ones of the drugs and metabolites will work most efficaciously in patients using specific drugs.
NanoMedicine:
Over the last couple of years, We have become increasingly interested in nanomedicine and have developed several interdisciplinary clinical translational research focused collaborations 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 specifically those pertaining to the dopaminergic pathway that includes a phosphor protein called “DARPP-32”. Targeting various key genes in the dopaminergic pathway results in the modulation of behavioral response which we observed in animal models of addiction/depression, 3) Biodistribution studies of various nanotherapeutic formulations using PET small animal imaging. Additionally, We are also focused on exploring epigenetic mechanisms that under drug addiction and mechanisms that underlie oxidative stress in neurodegenerative diseases.

Education and Training:

  • Postdoctoral Fellow, Immunology, University at Buffalo, The State University of New York (2001)
  • Postdoctoral Fellow, Metabolism/Endocrinology, Case Western Reserve University (CWRU) (1998)
  • PhD, Metabolism/Endocrinology, All India Institute of Medical Sciences (AIIMS) (1995)
  • MD, University of Bombay, India (1987)
  • BS, University of Bombay, India (1985)

Employment:

  • Research Associate Professor, Medicine, University at Buffalo (2015-present)
  • Research Assistant Professor, Medicine, University at Buffalo, The State University of New York (2002–2014)
  • Postdoctoral Research Associate, Medicine, University at Buffalo, The State University of New York (1998–2001)
  • Post Doctoral Fellow, Case Western Reserve University, Cleveland OH (1995–1998)
  • Pre-doctoral Research Fellow, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, India (1990–1995)
  • Research Fellow, Indo-USA NIH Funded Senior Fulbright Project (1993–1994)
  • Research Assistant, Department of Endocrinology and Metabolism, All India Institute of MedicalSciences, India (1988–1990)

Awards and Honors:

  • UB’s Faculty Internationalization Fund (2013)
  • US Fulbright Senior Scholar (2012) (2012)
  • NIDA Cutting-Edge Basic Research Awards (CEBRA) (2011)
  • NIDA Scholarship (2011)
  • NIDA Scholarship (2011)
  • Young Investigator Travel Award (2008)
  • Young Investigator award - International AIDS Society (2007)
  • College on Problems of Drug Dependence Young Investigator Award (2005)
  • International Union of Immunology Societies (IUIS) (2004)
  • Society for Neuro-Immune Pharmacology (2003)
  • INSERM Award (1992)
  • Travel Award from the Department of Science and Technology, Government of India (1990)

Research Expertise:

  • Blood Brain Barrier Research: We have validated both the 2 and 3 dimensional human in-vitro BBB models in my laboratory, that allowed examining permeability of virus, effects of drugs of abuse on BBB permeability, mechanisms of BBB transport, and tight junction modulation. My goal remains to determine the impact of current and potential CNS antiretrovirals, psychopharmacologic, and other medications on the integrity of the BBB in HIV associated neurological disorder and other neurodegenerative diseases. Additionally, I also investigate mechanisms that underlie drugs of abuse induced neuronal apoptosis.
  • HIV Neuropathogenesis: Dr. Mahajan has expertise in the area of HIV neuropathogenesis specifically in the context of drug abuse.
  • Nanomedicine: Nanotherapeutics for drug and gene delivery.
  • Systems Biology applications: Systems Biology analyses that allowed characterization of gene/ protein modulation in response to a drug stimulus or under a specific disease condition. I developed an expertise in these large-scale genomic and proteomic studies and the genomic studies helped identify key genes that underlie molecular mechanisms in drug addiction, HIV diseases progression, and allowed examination of the interplay of genes and environmental factors. The proteomic studies confirmed the presence of specific proteins that regulate key biological processes in drug addiction and HIV diseases progression.I expanded my investigations to include functional genomic/proteomic analyses that allowed characterization of gene/ protein modulation in response to a drug stimulus or under a specific disease condition. I developed an expertise in these large-scale genomic and proteomic studies and the genomic studies helped identify key genes that underlie molecular mechanisms in drug addiction, HIV diseases progression, and allowed examination of the interplay of genes and environmental factors. The proteomic studies confirmed the presence of specific proteins that regulate key biological processes in drug addiction and HIV diseases progression. Recently I have expanded my 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 small molecules (drugs and human/bacterial metabolites that are already a part of or continue to be added to the CANDO library. Using the CANDO Platform we are able to do the hierarchical fragment-based docking with dynamics between those compounds/drugs and the microbiome proteins/proteomes to determine which ones of the drugs and metabolites will work most efficaciously in patients using specific drugs.

Research Centers:

  • Clinical and Translational Research Center (CTRC)

Grants and Sponsored Research:

  • July 2010–June 2013
    Innovative Nanotherapy for Drug Addiction.
    Cutting-Edge Basic Research Awards (CEBRA)
    Role: Principal Investigator
    $250,961
  • February 2008–July 2012
    Effect of the SDF-1 3‘A Genetic variant on emergence of X4 tropism in Long Term Non-Progressors of HIV-1 disease.
    Pfizer
    Role: Principal Investigator
    $38,600
  • February 2012–June 2012
    Genetic basis for the increased incidence of HIV-1 associated lipodystrophy in the Indian HIV-1 subtype C patient cohort.
    US Scholars Core Fulbright Program
    Role: Principal Investigator

Patents:

  • Method of using gold nanorods-siRNA complexes Bioconjugation of Gold nanorods and DARPP-32 siRNA (2011)

Journal Articles:

See all (39 more)

Books and Book Chapters:

  • Mahajan SD, You Y, Aalinkeel R, Reynolds JL, Nair, Bindukumar B, Mammen MJ, Ignatowski TA, Cheng, Chong, Schwartz SA. Biodegradable Nanoparticle-Based Antiretroviral Therapy across the Blood-Brain Barrier. Handbook of Clinical Nanomedicine Nanoparticles, Imaging, Therapy, and Clinical Applications. 2016.
  • Mahajan SD, Aalinkeel R, Reynolds JL, Nair BB, Mammen MJ, Dai L, Prasad PN, Schwartz SA. Nanotechnology in Diagnosis, Treatment and Prophylaxis of Infectious Diseases. Nanotherapeutic Approach to Targeting HIV-1 in the CNS: Role of Tight Junction Permeability and Blood. 2015.

Professional Memberships:

  • BBB remodelling Conference; SUNY Funds requested for hosting scientific conference between SUNY Network (2016–present)

Presentations:

  • "Neurodegeneration associated with Methamphetamine Abuse" Colloquium, SUNY Albany, College of Arts and Science (2016)
  • "Nanotherapy for Drug addiction" CTRC Research Seminar, UB, CTRC Research Group (2014)
  • "HIV-1 disease progression" Center for Molecular Dynamics, Center for Molecular Dynamics, Center for Molecular Dynamics (2012)
  • "ART in India and its impact on HIV-1 associated Lipodystrophy" US- Fulbright, USIEF, US- Fulbright South Asian Meeting (2012)
  • "HIV-1 associated Lipodystrophy" Seminar National AIDS Resaerch Research Institute ( NARI), India, NARI, HIV pathophysiology (2012)
  • "Proteomic approach to evaluation of Disease Progression In Long Term Non Progressors (LTNP) of HIV-1 disease" Immunological Societies of Asia Oceania, FIMSA, FIMSA (2012)
  • "Nanotherapy for Drug addiction." International Conference on Molecular Medicine, Vellore Institute of Technology, MOLMED-2012 (2012)
  • "“Modulation of Tight junction expression by an MMP-9 nanoplex: Implications for maintaining Blood Brain Barrier integrity in HIV-1 encephalitis." International Symposium on HIV and Emerging Infectious Diseases., FIMSA, HIV and Emerging Infectious Diseases. (2010)
  • "Enhancing the Transversing Efficiency And Efficacy Of the Anti Retroviral Drug “Saquinavir” Using Nanotechnology: Implications For Nanotherapeutics In Neuro-Aids" 4th International Workshop on HIV-1 Persistance, HIV-1 resistance & Persistance, Nanotherapeutics In Neuro-Aids (2009)

Service Activities:

  • Faculty Senate; Member; Member (2015–2018)
  • Faculty Council; Member; Member (2014–2017)
  • Coordinator for Clinical trials for the Division of Allergy, Immunology & Rheumatology; Coordinator for Clinical trials for the Division of Allergy, Immunology & Rheumatology Ongoing trials in the Division GAM 5-28 Octagam Research trial Impact of Lung Flute Therapy on Asthma (completed); Advisor (2014–2015)
  • International Society of Neurovirology (ISNV); Member; Member (2014–present)
  • The Endocrine Society; Associate Member (2012–present)
  • VA Western New York Healthcare System- VA Research Day; Judge (2011)
  • American Society for Nanomedicine; Member (2010–present)
  • The International AIDS Society (IAS); Associate Member (2010–present)
  • The Society of NeuroImmune Pharmacology (SNIP); Member (2008–present)
  • Director of Research; Division of Allergy, Immunology & Rheumatology; Director (2006–present)
  • Reviewer for the Scientific journals; Journal Of Neuroimmune Pharmacology Nutrition AIDS Research & Therapy Expert Review of Endocrinology and Metabolism International Journal of Biomedical Science Nanomedicine BMC genomics AIDS Research and Human Retroviruses Research Reports in Clinical Cardiology Neurobehavioral HIV Medicine BMC Neurology International Journal of Nanomedicine African Journal of Pharmacy and Pharmacology Journal of Clinical Immunology Journal of the Taiwan Institute of Chemical Engineers Science of Advanced Materials European Food Research and Technology NANO Biomaterials Science; Reviewer (2006–present)
  • The Canadian Immunology Society - International Union of Immunology Societies, (IUIS); Member (2006–present)

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Contact Information

6074 UB‘s CTRC
Buffalo Niagara Medical Campus
875Ellicott Street
Buffalo, NY 14203
Phone: (716) 888-4776
Fax: (716) 859-1417
smahajan@buffalo.edu