Current & Recently Completed Research & Sponsored Projects
Epigenetics of the dysfunctional oral epithelium of PLWH and risk for HPV infection
Sponsor: NIH – NIDCR
PI: Dr. Aaron Weinberg
Period of Performance: 07/01/2023 – 06/30/2025
Summary: People living with HIV (PLWH) are at higher risk for oral warts and head and neck cancer due primarily to higher incidences of human papilloma virus (HPV) infections that are contracted orally by compromised cells in the lining of the mouth. Our research has shown that these cells are epigenetically modified, i.e., that either chronic HIV infection and/or the antiretroviral therapy is/are altering certain genes without altering their DNA. By identifying these alterations, determining their effect on gene expression and seeing if they contribute to increased risk of HPV infection, we will drive the discovery and application of novel epigenomic-based clinical interventions in PLWH.
Innate and adaptive defenses against SARS-COV-2 in the oral cavity during acute unvaccinated and breakthrough infections
Sponsor: NIH – NIDCR
PI: Dr. Aaron Weinberg
Period of Performance: 09/01/2022 – 08/31/2023
Summary: Variants of the COVID-19 virus are challenging our healthcare system, in spite of the success of vaccines, with some leading to increased hospitalizations of unvaccinated individuals as well as accelerating “breakthrough” infections. Since the mouth is a primary site for infection by the virus, we believe that saliva and cells brushed from virally infected tongues of people during the early stages of infection will reveal important protective immune markers that can be exploited in the future to develop more effective strategies to block new infections. We will recruit early-infected unvaccinated and breakthrough individuals to: 1) compare results with those from healthy vaccinated people, 2) identify viral variants and see if they, along with age and sex, affect oral protective markers differently and 3) develop new and rapid tests to quantify viral infection in the mouth.
Amphiregulin-Immunometabolism axis in oral immunity and inflammation during HIV infection
(Renewal of "Mechanisms of Th17 and Treg Cells Dysregulation in Oral Mucosal Inflammation During HIV Disease")
Sponsor: NIH – NIDCR
PI: Dr. Pushpa Pandiyan
Period of Performance: 04/01/2017 – 05/31/2027
Summary: Systemic inflammation and mortality in people living with HIV (PLWH) are associated with mucosal immune dysfunction and persistent viral reservoirs in the mucosa and lymphoid tissues. Our proposal determines the underlying mechanism of immunological dysfunction in the mouth and will reveal new directions to address oral disease and systemic inflammation n PLWH.
Cleveland Digestive Diseases Research Core Center Pilot Award
Sponsor: CDDRC (prime funding from NIH)
PI: Dr. Pushpa Pandiyan
Period of Performance: 02/01/2022 - 01/31/2023
Summary: This study will find out how HIV infection speeds up transition of oral lesions to cancer and identify new therapeutic strategies to intervene HIV-associated oral diseases in the population.
Role of HIV in KSHV Oral Transmission
Sponsor: NIH – NCI
PI: Dr. Ge Jin
Period of Performance: 09/20/2021 – 08/31/2026
Summary: Kaposi sarcoma herpesvirus (KSHV) infection can cause Kaposi’s sarcoma (KS), a major malignancy leads to mortality and morbidity in people living with HIV/AIDS. Saliva from people with HIV infection contains nanoparticle-like extracellular vesicles that increase KSHV infection. This research will help us find a new method to prevent KSHV infection and transmission in populations living with HIV and people with high HIV infection risks.
Premalignant oral lesions in people living with HIV
Sponsor: NIH – NIDCR
PI: Dr. Ge Jin
Period of Performance: 09/24/2021 – 09/23/2022
Summary: This study will find out how HIV infection speeds up transition of oral lesions to cancer and identify new therapeutic strategies to intervene HIV-associated oral diseases in the population.
Immunoregulation in setting of COVID
Sponsor: Louis Stokes Cleveland VA Medical Center
PI: Dr. Pushpa Pandiyan
Period of Performance: 1/01/2020 - 10/30/2023
Microfluidic Intact Cell Platform: A Novel Tool for Oral Cancer Detection
Sponsor: NIH – NCI
PI: Dr. Aaron Weinberg
Period of Performance: 08/01/2020 – 07/31/2023
Summary: Oral cancer (OC) kills thousands in the U.S. and hundreds of thousands worldwide, and early detection is key to improved survival. Since biopsy followed by pathology review, the gold standard for OC, is costly, painful, can result in patient complications, is impractical should monitoring be required, and is often not available or imprecise in third world countries, we intend to develop (Aim 1), and test in humans (Aim 2), an innovative device that will accurately detect OC, non-invasively, within ½ hour and thereby will address a major unmet need in early OC detection worldwide. The device will incorporate microfluidic, imaging and computational technologies that will determine the ratios of two key proteins from swabbed cells obtained from suspicious oral lesions; a procedure we have already shown to be accurate using a laboratory based technique.
HIV-Infected T-Cell Exosomes in Lung Cancer Progression
Sponsor: NIH – NCI
PI: Dr. Ge Jin
Period of Performance: 07/01/2020 - 06/30/2025
Summary: Lung cancer is the second most common malignancy in the US with Human immunodeficiency virus (HIV)-infected individuals and AIDS patients at increased relative risk by 250% and younger diagnosis. HIV-infected cells secrete extracellular vesicles, such as exosomes, into the blood and other body fluids which we found to stimulate lung cancer growth in HIV-infected persons. This research will help us understand why and how HIV-associated exosomes promote cancer and find a new method to control lung cancer development and progression in the population of persons living with HIV.
Oral Immune Plasticity, HIV-Infected T Cell Extracellular Vesicles, and Oral Cancer
Sponsor: NIH – NIDCR
PI: Dr. Ge Jin
Period of Performance: 05/01/2017 – 02/28/2023
Summary: HIV-infected individuals under combination antiretroviral therapy (cART) have more oral cancer cases than those in the general population. HIV-infected cells secrete nanoparticle-like extracellular vesicles (EVs), which contain proteins, lipids, and RNA to influence many diseases, including cancer. We found that HIV-infected T cells produce EVs that stimulate oral cancer cell proliferation and tumor progression. This proposed research will help us understand why and how HIV-infected T cell EVs promote oral cancer and find a new method to control oral cancer development in the chronically HIV-infected population.
Recently Completed Research Projects
hBD-3: A novel Factor Orchestrating Microbial Persistence in Suspicious Oral Lesions
Sponsor: NIH – NIDCR
PI: Dr. Aaron Weinberg
Period of Performance: 08/01/2019 – 05/31/2022
Summary: It is becoming more evident, by studying bacterial communities (microbiome studies), that certain bacteria belonging to a group called Fusobacteria are playing a role in promoting oral cancer. We have identified that a specific protein that kills bacteria – human beta defensin 3 (hBD-3) – that is overexpressed in oral cancer cells can be used to distinguish cancerous lesions from non-cancerous ones. We hypothesize that overexpression of hBD-3 in oral cancer promotes selective persistence of Fusobacteria that are resistant to hBD-3. We intend to recruit subjects with suspicious oral lesions and (1) distinguish cancer from non-cancer by determining the level of hBD-3, (2) conduct microbiome analysis to correlate high hBD-3 levels with specific retentive bacteria which we suspect will belong to organisms belonging to Fusobacterium, and (3) isolate hBD-3 resistant fusobacterial organisms from the cancer sites and compare them to non-cancer sites.
Immunosuppressive cells and propensity to OSCC
Sponsor: CWRU Comprehensive Cancer Center ( funded by NIH – NCI)
PI: Dr. Pushpa Pandiyan
Period of Performance: 04/01/2020 - 03/31/2021
Identification and Elimination of HIV Reservoirs in Oral Lymphoid Tissues by Engineered NK Cells
Sponsor: NIH – NIDCR
Co-Investigator: Dr. Pushpa Pandiyan (Lead PI: Dr. Jonathan Karn, School of Medicine)
Period of Performance: 08/01/2015 – 07/31/2020
Summary: In the United States at least 1 million people are living with AIDS and require life-long treatment with antiretroviral drugs because HIV can remain silent in some cells, referred to as latent infection. Here we will be developing a strategy to identify and eliminate those latent cells that reside in the oral cavity using immune cells derived from the infected patients known as Natural Killer (NK) cells. Eradication of the latent cells provides a functional cure for the patients and will allow them to discontinue costly drug therapy.
Head and Neck Cancer, Beta-Defensins, and Immune Responses
Sponsor: NIH – NIDCR
PI: Dr. Ge Jin
Period of Performance: 07/01/2015 – 06/30/2021
Summary: Head and neck cancer accounts for 3-5% of all malignancies in the US, corresponding to over 50,000 new cases and more than 10,000 deaths each year. Despite our improved understanding of the cancer and advances in therapeutics, the 5-year survival rate of oral cancer remains low at about 50-60%. The proposed research is expected to help us understand how head and neck cancer-released peptides promote cancer growth and progression through triggering a set of tumor-promoting immune responses, which will eventually lead to uncover new targets for immunotherapeutic interventions for this deadly disease.
Point-of-Care Device for Diagnosis and Monitoring of Oral Cancer
Sponsor: CWRU Technology Validation and Start-Up Fund via the Ohio Development Services Agency
PI: Dr. Aaron Weinberg
Period of Performance: 01/01/2018 – 12/31/2019
Summary: Validation of a microfluidic-based point-of-care device to determine the presence of cancer in suspicious oral lesions.