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Faculty Research Staff at MetroHealth Medical Center
Professor in the Department of Medicine at CWRU
Member of Case Comprehensive Cancer Center
MetroHealth Medical Center
Rammelkamp Center for Research
2500 MetroHealth Drive, Cleveland, OH 44109
The long-term goal of research in the Jin laboratory is to better understand progression of cancers in the context of viral infection, including HIV and etiological viruses, for the development of effect therapeutic approaches to combat the disease. We have reported that exosomes, extracellular vesicles (EVs) of endosomal origin, released by HIV-infected T cells promote proliferation, migration, and invasion of head and neck as well as lung cancer cells. Plasma exosomes purified from people with HIV stimulate cancer cell proliferation and invasion.
However, exosome depletion abolishes the tumor-promoting effects. HIV-associated exosomes also promote infectivity of Kaposi sarcoma-associated herpesvirus (KSHV), an etiological factor for Kaposi’s sarcoma (KS) that is a major malignancy leading to mortality and morbidity in people living with HIV/AIDS, in the oral cavity. Saliva exosomes from people with HIV infection increase KSHV infection. HIV-associated exosomes from T cells interact with epidermal growth factor receptor (EGFR) of cancer cells and stimulate phosphorylation of ERK1/2 and p38, without causing activation of EGFR. Cetuximab, a monoclonal antibody to EGFR, and tyrosine kinase inhibitors effectively block proliferation of cancer cells and inhibit KSHV infectivity in oral epithelial cells induced by HIV-associated exosomes. In addition, oral cancer cells overexpress human beta-defensin-3 (HBD3), a secreted innate immune peptide.
Human papillomavirus (HPV) associated head and neck cancer also express HBD3. We have reported that expression of HBD3 is induced by activation EGFR, WNT signaling, and by inactivation of the tumor suppressor p53 - all three pathways that are implicated in cancer development. Data indicates that tumoral expression of HBD3 is not an immune response during tumorigenesis; the peptide interacts with EGFR and other EGFR family members of cancer cells to induce the MAPK signaling, contributing to tumor progression.
Dr. Jin received his PhD degree in Cell Biology from the Department of Physiology & Biophysics, Case Western Reserve University School of Medicine in 2000, where he studied TGFβ signaling in cancer cells. He received postdoctoral training at Department of Molecular Biology, the Learner Research Institute, Cleveland Clinic. Before join the MetroHealth System, he was a professor in the Department of Biological Sciences, Case Western Reserve University School of Dental Medicine. In 2022, he was appointed to professor at Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine.
Chen L, Feng Z, Yue H, Bazdar G, Mbonye U, Zender C, Harding CV, Bruggeman L, Karn J, Sieg SF, Wang B, Jin G (2018). Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat Commun. PMID: 30389917 PMCID: PMC6214989.
Chen L, Feng Z, Yuan G, Emerson CC, Stewart PL, Ye F, Jin G (2020). Human Immunodeficiency Virus-Associated Exosomes Promote Kaposi's Sarcoma-Associated Herpesvirus Infection via the Epidermal Growth Factor Receptor. J Virol. PMID: 32051269 PMCID: PMC7163124
Chen L, Chen R, Yao M, Feng Z, Yuan G, Ye F, Nguyen K, Karn J, McComsey GA, McIntyre TM, Jin G (2022). COVID-19 plasma exosomes promote proinflammatory immune responses in peripheral blood mononuclear cells. Sci Rep. PMID: 36526691 PMCID: PMC9756928.>