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• Nominated for the Elizabeth Bingham Mentoring Award by a former MD/PhD student (2024)
• Recipient of AAI Laboratory Travel Award consistently for four years to attend Immunology 2024 - Chicago, USA, May 3-7 (2024)
• Nominated for the DrexelMed 2024 Award for Excellence in Basic Science Mentoring, Philadelphia, PA, USA (2024)
• Chair, 22nd Biennial Conference on Retrovirology; HTLV and related viruses to be organized in USA after two decades (2024)
• Nominated for the International faculty award by the International Retrovirology Association (IRVA) (2024)
• Elected member in Alpha Omega Alpha (AOA) Medical Honor Society, Delta Zeta Chapter & Gold Humanism Honor Society by the Arnold P. Gold Foundation. Induction ceremony, Philadelphia, Pa., USA. March 22 (2023)
• Recipient 20-year service award by the 91制片厂 at the Service Recognition reception, Philadelphia, PA, USA. January 18 (2023)
• Received institutional pilot Open Access Publishing Fund ($2000) toward the article processing charges for the Drexel scholars (2022)
• Laboratory travel grant ($2500) by the American Association of Immunologists (AAI) to deliver a talk at Immunology 2022, Portland, OR, USA, May 6-10 (2022)
• Nomination for the Basic Science Research Award by the International Retrovirology Association (IRVA) (2022)

• Full member of the Immune Cell Regulation & Targeting (IRT) Program of Excellence at the Sidney Kimmel Cancer Center, TJU, Philadelphia, Pa. (2022–present)
• American Society for Exosomes and Microvesicles (ASEMV) (2020–present)
• Elected member of the American Society of Hematology (ASH) (2019–present)
• International Retrovirology Association (IRVA) (2014–present)
• American Asian Pacific Islander (AAPI), a National Institute of Drugs Abuse (NIDA/NIH) supported group (2012–present)
• National Association of Professional Women (NAPW) (2010–present)
• International Society for Dendritic Cell & Vaccine Science, Life Member (2010–present)
• Society for Leukocyte Biology, USA (2009–present)
• Women in Neurovirology Committee, USA (2009–present)
• American Society of Microbiology (ASM) (2002–present)
• International Society for Neurovirology (ISNV), USA (2003–present)
• American Society of Virology (ASV) (2006–present)
• International Society for Neuroimmunology (ISNI), USA (2006–present)
• The American Association of Immunologists (AAI) (2009–present)
• Society on NeuroImmune Pharmacology (SNIP), USA (2009–present)

Graduate students: Salwa Ahmed, MS candidate; Noor Qureshi, MD candidate

Research staff: Dr. Cabirou Shintouo, research associate

Project #1: Define risk factors associated with people living with HIV (PLWH) that contribute to AIDS defining cancers including Burkitt鈥檚 lymphoma and diffuse large B-cell lymphoma.

Lymphomas are closely associated with the history of oncoviruses. Epstein-Barr virus (EBV) is known as a common factor in many of AIDS-related cancers (ADCs), including Burkitt鈥檚 lymphoma and diffuse large B-cell lymphoma. The latent cycle of EBV regulates the development of EBV-associated lymphomas. This project investigates the effects of various factors associated with people living with HIV/AIDS (PLWH) which impact EBV latency in cooperation with the cellular oncoproteins such as members of myocyte enhancer factor (MEF)-2 family that others and we have established as major carcinogenic factors in a variety of leukemias and lymphomas. In the developed world, most individuals infected with HIV are on antiretroviral therapy (ART), which is not able to eradicate HIV or cure the infection, meaning that patients must adhere strictly to treatment. The consistent presence of soluble HIV proteins and prolonged ART use has its own health risks, including an increased risk of cancer. Similarly, oncogenesis is prevalent among substance users. However, the exact mechanisms linking drugs of abuse and cancer remain unclear. Our study investigates the underlying mechanisms that promote oncogenesis in populations using ART and/or substances of abuse, with a focus on the activation of cancer-associated viruses, such as EBV.

Project #2: Targeting MEF-2 signaling as a therapeutic strategy for T-cell leukemia/lymphoma.

About 15 million people are infected with Human T-cell leukemia virus type 1 (HTLV-1, the very first human retrovirus identified) and many millions with HTLV-2 worldwide. The surprisingly recent detection of high prevalence rates among the indigenous people of central Australia has raised a new alarm and heightened attention to HTLV infection and associated malignancies termed ATLL (adult T-cell leukemia/ lymphoma), emphasizing the important public health issues that have yet to be addressed. This proposal will investigate the role of a novel target MEF-2 in promoting ATLL pathogenesis and elucidate the mechanism by which this protein influence ATL severity and chemoresistance, providing the opportunity to develop efficacious therapeutic interventions.

HTLV-1, the first retrovirus identified to directly cause human cancer is the most carcinogenic human oncovirus and does not currently have an effective treatment or vaccine. Our ongoing studies are a relevant continuation of our original findings and will reveal new information with respect to HTLV-1 antisense transcription and viral oncogenesis while moving forward the field of retroviral (e.g. HIV-1, HTLV-2, etc.) antisense transcription.

Project #3: Exosomes and ESCRT machinery in Neuroinflammation Caused by Retrovirus Infection.

Exosomes are small extracellular vesicles (sEVs, 50-200nm) that are involved in complex intercellular communication via diverse cargo consisting of lipids, nucleic acids, and proteins. Exosomes play important roles in cancer, virus infection and neurological diseases. Infection with HTLV-1 also causes HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), with pathological parallels to both Multiple Sclerosis and HIV-associated neurocognitive disorder (HAND). Infection is carried to the central nervous system (CNS) by infected CD4 T cells and chronically activated CD8 T cells that are primed against HTLV-1 but can also recognize myelin antigens (molecular mimicry) creating an autoimmune condition in the CNS. This complex neuroimmune pathogenesis is incompletely understood, and there is no effective treatment, vaccine or cure is available.

Over the years, our laboratory has made tremendous efforts in understanding the root cause of neuroinflammation and observed that T cells from HAM/TSP patients spontaneously proliferate and consistently express high levels of negative checkpoint receptors (NCRs) such as PD-1/PD-L1, LAG-3, Tim-3 and TIGIT. Elevated presence of these immune checkpoint (ICP) mediators inhibits cytolytic activity of HTLV-specific T cells contributing to high proviral load and chronic antigen exposure with viral proteins, Tax and HBZ. Interestingly, these proteins along with unique cytokines and NCRs are released in soluble and exosomal forms in HAM/TSP sera and play important role in the neuro/immunopathognesis.

Exosomes originate from the multivesicular bodies (MVBs), transported/fused with the membrane, and released into the extracellular space depending upon physiological condition and the ESCRT machinery. The ESCRT machinery is made of peripheral protein complexes (ESCRT-0, -I, -II, -III VPS4-VTA1, and ALIX homodimer) that are successively recruited by late endosomes to form the MVB. Typically, the ESCRT machinery is involved in the inward abscission of membranes, and enveloped viruses such as HIV-1 reprograms this machinery to facilitate viral budding thru 鈥渞everse topology.鈥� More so, ESCRT proteins were enriched in PD-L1鈥檚 proximal proteome, and EV biogenesis was affected by anti-PD-L1 treatment, suggesting a link between ICPs and ESCRT. We hypothesize that ESCRT machinery play critical role in release of exosomes from HTLV-infected cells with specific cargo that contribute to neuroinflammation via viral RNA/protein, proinflammatory cytokines, and co-inhibitory receptors. These innovative studies intend to establish role of exosomes and soluble checkpoint mediators in a neuroinflammatory disease caused by retroviral infection providing new clues for future therapeutic development.

Videos

and by rolling or capturing with the inflamed spinal cord microvasculature in SJL mice with EAE.

and to the inflamed spinal cord white matter microvasculature in SJL mice with EAE.

Selected Publications

鈥淐yclin D dependent dendritic cell differentiation is correlated with decreases in Wnt signaling and increases in DNA methylation鈥�
Ginwala, R., Deak, P., Chigbu, D., Patel, D., Kawasawa, Y, Pestell, R., and P. Jain
Genes and Immunity, submitted, 2024

鈥淐haracterization of HTLV-1 Infectious molecular clone isolated from patient with HAM/TSP and immortalization of human primary T cell lines鈥�
Bellon, M., Jain, P., and C. Nicot
Viruses, 16, 1-22, 2024

Joseph, J., Premeaux, T., Tandon, R., Murphy, E., Bruhn, R., Nicot, C., Herrera, B., Lemenze, A., Altrash, R., Tonto, P., Ndhlovu, L., and P. Jain
Viruses, Special Issue 鈥淗uman T-cell Leukemia Virus infection and Treatment鈥�, 16(9): 1443-1462 (2024)

Darchiashvili, S., Kulkarni, R., Tandon, R., Deek, P., Ngyun, K., and P. Jain
NeuroImmune Pharmacology and Therapeutics, published online (July 2024)

Smith, S., Seth, J., Midkiff, A., Stahl, R., Syu, Yu-Ci, Kvaratskhelia, M., Forsyth, K., Jain, P., Green, P., and A. R. Panfil
International Journal of Molecular Sciences (IJMS), 24: 13119-13139 (2023)

Additional publications...

Book

P. Jain (Chief Editor) and L. Ndhlovu (Co-editor)
Springer International Publishing; 2020. DOI:10.1007/978-3-030-33946-3_1 ISBN: 9783030339456(1)

Book Chapters

鈥淒evelopment of Experiential Learning Projects in the Online Educational Environment鈥�
P. Norton, E. Mosser, P. Jain, F. Krebs, S. Jennings
EDULEARN23: 15th annual International Conference on Education and New Learning Technologies, Palma de Mallorca, Spain (July 2023)

鈥淭ransgenic Animals in Research and Industry鈥�
Masih, S., Kamal, S., Jain, P., and Z. K. Khan
Chapter 21, pp. 407-423. Elsevier Science Publications, edited book Animal Biotechnology: Models in Discovery and Translation, 2nd Advance Edition (2020)

Hoffman, M., Chigbu, D., Crumley, B., Sharma, R., Pustylnikov, S., Crilley, T., Loonawat, R., Joseph, J., Sales, D., Wilson, D., Ginwala, R., and P. Jain
In the Edited Book (P. Jain and L. Ndhlovu, editors) Advanced Concepts in Human Immunology: Prospects for Disease Control. Springer International Publishing. (2020)

“Immune Mechanisms, Pathology, and Management of Allergic Ocular Diseases”
Chigbu, D., Jain, P., and Z. K. Khan
In the Edited Book (P. Jain and L. Ndhlovu, editors) Advanced Concepts in Human Immunology: Prospects for Disease Control. Springer International Publishing. DOI:10.1007/978-3-030-33946-3_1 ISBN: 9783030339456(1) (2020)

“Transgenic Animals in Research and Industry”
Masih, S., Kamal, S., Jain, P., and Z. K. Khan
Chapter 21, pp. 407-423. Elsevier Science Publications, edited book Animal Biotechnology: Models in Discovery and Translation, 2nd Advance Edition (2020)

Additional book chapters...

Editorial and Commentary

Handling Editor, special issue on the topic "Cancer in People living with HIV/AIDS" for Frontiers in Cellular and Infection Microbiology (2023-)

Mulherkar, T., Ginwala, R., Khan, Z. K., and P. Jain
Journal of AIDS and HIV Treatment, 3(3): 49-53 (2021)

Dave, R., Jain, P., and S. Byrareddy
Commentary in Journal of Neuroimmune Pharmacology, 13(2): 123-125 (2018)

Shapiro, V., Kovats, S., Parent, M., Gaffen, S., Hedrick, C. Jain, P., Denzin, L., Raghavan, M., and R. Stephens
Journal of Immunology, 197: 3751-3753 (2016)

Saito, M., Jain, P., Tsukasaki, K., and C. R. M. Bangham
Leukemia Research and Treatment (2012)

鈥淭he long-distance control of immunity by the retroviral antisense protein via exosomes鈥�
American Society for Intercellular Communications (ASIC) webinar (June 21, 2024)

鈥淲orkshop 4鈥�
Invited talk on the overview of exosome-related studies in the field of HTLV research during the 21st Biennial International Conference on Human retrovirology: HTLV and related viruses at the Imperial College/Royal College of Physicians, London (June 4, 2024)

鈥淟ong distance control of immunity by HBZ via exosomes鈥�
Invited talk during HTLV2024: The 21st Biennial International Conference on Human retrovirology: HTLV and related viruses at the Imperial College/Royal College of Physicians, London (June 4, 2024)

鈥淣ovel therapeutic strategies for HIV cure and neuroinflammation鈥�
Invited seminar at the Reddy鈥檚 laboratories, Hyderabad, India. March 29, 2024. Invited seminar at the Rush Medical Center, Chicago, USA (May 6, 2024)

鈥淭he MAPK/ERK-regulated MEF-2 isoforms as novel therapeutic target for a rare form of retrovirus-induced leukemia/lymphoma 鈥� ATLL鈥�
Invited talk at the 8th World Cancer Congress 鈥� 2024, JNU Convention Centre, New Delhi, India (March 19, 2024)

Additional presentations...