The primary goal of this COBRE is to strengthen the biomedical research infrastructure in Louisiana by training Promising Junior Investigators (PJIs) who can develop independent research addressing a major health problem in our region. Virus-associated cancers remain a major cause of morbidity and mortality in our region and disproportionately affect the African American population. These include HPV- associated cervical, anogenital, and head and neck cancers, KSHV-associated Kaposi sarcoma and primary effusion lymphoma, HCV- and HBV-associated liver cancers and others, all which are unusually highly prevalent in our area. Increases in these diseases may be explained, in part, by the large number of HIV-infected patients in the region. In addition, our data also indicate that co-infection of cells with more than one virus promotes or associates with malignant transformation. Therefore, understanding how particular viruses and viral co- infections promote the development of malignancies is essential to identifying and implementing new preventative, diagnostic and treatment strategies. It follows that training a new cadre of investigators capable of conducting novel research in the field of viral oncology is essential for our state. This will be accomplished by developing a Center for Translational Viral Oncology (CTVO) that leverages existing resources in order to train new investigators, develops novel laboratory infrastructure, and supports research projects designed to study these diseases in our unique populations. The CTVO will support the scientific, mentoring and administrative needs of the PJIs by providing (i) experienced mentoring teams composed of NIH-funded and internationally recognized investigators who are committed to guiding PJIs in developing cutting edge research, ensuring their successful training, and supporting their development as independent researchers; (ii) unique clinical material from high risk patient populations ? PJIs will have preferential access to a unique (and increasing) set of clinically annotated biospecimens from HIV+ and HIV- patients with virus-associated cancers collected at the University Medical Center ? New Orleans (iii) well-established administrative and cutting edge scientific infrastructure including integrated cancer and HIV clinical trials programs to translate the findings of these projects, advanced core research laboratories, and a new expanded and unique biorepository, the HIV/Clinical Tumor Biorepository (HCTB) Core. Initially, this COBRE brings four projects led by PJIs to study the role of oncogenic viruses such as HPV, KSHV and EBV, as well as, viruses of increasing interest in human carcinogenesis such as human cytomegalovirus (HCMV), human endogenous retrovirus sequences (HERVs), and human neurotropic Polyomavirus JC (JCV). These cancers arise more commonly in the setting of immune deficiencies (including HIV infection), and disproportionately affect African American patients in Louisiana. Implementation of the proposed work will be directed by the following Specific Aims: 1) to establish interdisciplinary teams of investigators and laboratory core infrastructure to support PJI-led research projects on virus-host interactions and their role in pathogenesis of cancer; 2) to develop an administrative infrastructure to mentor and promote the independent career of the PJIs; and 3) to leverage institutional NIH-funded Centers and Programs at the participating institutions to facilitate the integration of PJIs within the clinical and translational research infrastructure. The completion of this program will provide this region with enhanced capabilities to address these and other virus related health problems that may arise in the future.

Public Health Relevance

Viruses are responsible for approximately 20% of all human cancers. Understanding the mechanisms by which viral infection dysregulates cell functions is essential for the development of new diagnostic and therapeutic approaches for virus- induced cancers. We will support four promising junior investigators who will study molecular details of virus-host interactions while using patient samples, clinical data, and/or relevant biologic systems to facilitate clinical translation of their most promising research findings.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM121288-03
Application #
9726012
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Bernal, Federico
Project Start
2017-08-15
Project End
2022-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Mills, Kylie L; Gomes, Angelica M; Standlee, Courtney R et al. (2018) Gas6 is dispensable for pubertal mammary gland development. PLoS One 13:e0208550
Lassak, Adam; Dean, Mathew; Wyczechowska, Dorota et al. (2018) Molecular and Structural Traits of Insulin Receptor Substrate 1/LC3 Nuclear Structures and Their Role in Autophagy Control and Tumor Cell Survival. Mol Cell Biol 38:
Qiao, Jing; Cao, Yueyu; Zabaleta, Jovanny et al. (2018) Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules. J Virol 92:
Dai, Lu; Del Valle, Luis; Miley, Wendell et al. (2018) Transactivation of human endogenous retrovirus K (HERV-K) by KSHV promotes Kaposi's sarcoma development. Oncogene 37:4534-4545
Dai, Lu; Smith, Charles D; Foroozesh, Maryam et al. (2018) The sphingosine kinase 2 inhibitor ABC294640 displays anti-non-small cell lung cancer activities in vitro and in vivo. Int J Cancer 142:2153-2162
Dai, Lu; Qiao, Jing; Del Valle, Luis et al. (2018) KSHV co-infection regulates HPV16+ cervical cancer cells pathogenesis in vitro and in vivo. Am J Cancer Res 8:708-714
Lin, Zhen; Nguyen, Christian; Xu, Beibei et al. (2018) Interleukin-17A in the Pathogenesis of Lung Adenocarcinoma. Ann Am Thorac Soc 15:S125
Ungerleider, Nathan; Concha, Monica; Lin, Zhen et al. (2018) The Epstein Barr virus circRNAome. PLoS Pathog 14:e1007206
Dai, Lu; Zhao, Mengmeng; Jiang, Wei et al. (2018) KSHV co-infection, a new co-factor for HPV-related cervical carcinogenesis? Am J Cancer Res 8:2176-2184
Dai, Lu; Lin, Zhen; Jiang, Wei et al. (2017) Lipids, lipid metabolism and Kaposi's sarcoma-associated herpesvirus pathogenesis. Virol Sin 32:369-375

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