91制片厂

• Nominated for the Elizabeth Bingham Mentoring Award by a former MD/PhD student (2024)
• Recipient of the AAI Laboratory Travel Award consistently for four years to attend Immunology 2024 - Chicago, Illinoios, May 3-7 (2024)
• Nominated for the 91制片厂 2024 Award for Excellence in Basic Science Mentoring, Philadelphia, Pennsylvania (2024)
• Chair, 22nd Biennial Conference on Retrovirology: HTLV and Related Viruses (2024)
• Nominated for the international faculty award by the International Retrovirology Association (IRVA) (2024)
• Elected member of the Alpha Omega Alpha (AOA) Honor Medical Society, Delta Zeta Chapter and the Gold Humanism Honor Society by the Arnold P. Gold Foundation (2023)
• Recipient of a 20-year service award from 91制片厂 (2023)
• Received institutional pilot grant from the Open Access Publishing Fund ($2,000) toward the article processing charges for Drexel scholars (2022)
• Laboratory travel grant ($2,500) from the American Association of Immunologists (AAI) to deliver a talk at Immunology 2022, Portland, Oregon (2022)
• Nominated 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, Pensylvania (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: Michelle Borisov (MS), Elizaveta Valovatsky (MS), Zeel Patel (MS), Sai Gaekwar (MS), Deema Alhamada (MS), Pranav Arora (BS), Aditi Sunil (BS), Saanika Acharya (BS)

Research staff: Ryan Hoffman, lab manager/research assistant

Project #1: Cell and gene therapy for non-Hodgkin lymphoma.

Understanding CAR T-cell and gene therapy approaches for adult T cell leukemia/lymphoma (ATLL) within the broader context of non-Hodgkin lymphoma is essential for improving therapeutic precision and efficacy. This project investigates the application of advanced cell and gene therapy strategies, with a focus on harnessing antigen-specific T cell responses to enhance targeted tumor elimination. We examine how in vivo selection of T cell receptor (TCR) sequences — particularly within the CDR3 region — drives specificity toward peptide-MHC complexes, providing a molecular basis for precise antigen recognition. These insights guide the rational design of engineered T cells, including CAR-T and TCR-T therapies, by identifying key sequence motifs that strengthen tumor targeting. In addition, we explore how antigen-driven clonal expansion of cytotoxic T cells can be leveraged to generate durable and sustained anti-tumor immunity. The project also addresses the critical balance between effective cytotoxic function and the risk of excessive inflammatory signaling, which may impact treatment safety and patient outcomes. By integrating detailed molecular characterization of TCR specificity with cutting-edge gene engineering approaches, we aim to optimize T cell persistence, targeting accuracy and functional potency. Ultimately, our study seeks to advance next-generation immunotherapies that offer more selective, durable and safe control of non-Hodgkin lymphoma.

Project #2: Define risk factors associated with people living with HIV (PLWH) that contribute to AIDS-defining cancers including Burkitt’s lymphoma and diffuse large B cell lymphoma.

Lymphomas are closely associated with a history of oncoviruses. Epstein-Barr virus (EBV) is known as a common factor in many AIDS-defining cancers (ADCs), including Burkitt’s 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) that impact EBV latency in cooperation with cellular oncoproteins, such as members of myocyte enhancer factor (MEF)-2 family, which researchers 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 #3: 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 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 influences ATLL 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 #4: 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 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 an important role in the neuro/immunopathogenesis.
Exosomes originate from the multivesicular bodies (MVBs), are transported/fused with the membrane, and then 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 through “reverse topology.” More so, ESCRT proteins were enriched in PD-L1’s proximal proteome, and EV biogenesis was affected by anti-PD-L1 treatment, suggesting a link between ICPs and ESCRT. We hypothesize that ESCRT machinery plays a 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 the 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.

Publications

Selected Publications

Editorial and Commentary

“The long-distance control of immunity by the retroviral antisense protein via exosomes”
American Society for Intercellular Communications (ASIC) webinar (June 21, 2024)

“Workshop 4”
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)

“Long distance control of immunity by HBZ via exosomes”
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)

“Novel therapeutic strategies for HIV cure and neuroinflammation”
Invited seminar at the Reddy’s laboratories, Hyderabad, India. March 29, 2024. Invited seminar at the Rush Medical Center, Chicago, USA (May 6, 2024)

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

Additional presentations...