Project 1 - Molecular Genetics of Human Papillomavirus Infection and Oncogenesis

项目 1 - 人乳头瘤病毒感染和肿瘤发生的分子遗传学

• 批准号: 10910335
• 负责人: PAUL F. LAMBERT
• 金额: $ 15.45万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10910335
• 关键词: Anogenital cancer; Biology; Cells; Cervical; Chemicals; Collaborations; Cutaneous; Data; Development; Disease; Disease model; Environment; Epithelium; Estrogens; Etiology; Event; Fanconi' s Anemia; Funding; Genes; Genetic Diseases; Head and Neck Cancer; Herpesviridae; Human; Human Genetics; Human Papillomavirus; Human papilloma virus infection; Immune; Immune system; Immunosuppression; Infection; Integration Host Factors; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Molecular; Molecular Biology; Molecular Genetics; Mucous Membrane; Mus; Mutation; Oncogenic Viruses; Oral; Organ Transplantation; Papilloma; Papillomavirus; Pathologic; Patients; Role; Skin; Skin Cancer; Stromal Neoplasm; Study models; Testing; The Cancer Genome Atlas; Transplant Recipients; Viral; cervical carcinogenesis; epithelial stem cell; high risk; human papilloma virus oncogene; insight; keratinocyte; mouse model; neoplastic; novel strategies; prevent; skin disorder; tumor microenvironment; tumorigenesis

PROJECT 1 − SUMMARY/ABSTRACT A subset of human papillomaviruses (HPVs) cause 5% of human cancers including the majority of cervical cancers. Over the current funding period, we discovered that interactions between the cervical epithelium and its stromal tumor environment are key to cervical carcinogenesis. We will test specific hypotheses for how the tumor microenvironment contributes to cervical carcinogenesis. We will also evaluate the role of mutations in cellular genes in cervical carcinogenesis based upon insights gained from The Cancer Genome Atlas initiative, and identify mutations in cancer related genes that cause cervical cancers arising in FA patients to become HPV-independent. In the second aim we will continue utilizing the recently discovered mouse papillomavirus MmuPV1 to investigate the role of high risk cutaneous HPVs in neoplastic skin disease, as seen in patients with epidermodysplasia verrucoformis, using powerful new mouse models for that disease developed in our labs. We will also study the importance of immunosuppression and epithelial progenitor cells in papillomavirus induced skin disease.

项目1-概要/摘要 人乳头瘤病毒（HPV）的一个子集导致5%的人类癌症，包括大多数宫颈癌。 癌的在目前的资助期间，我们发现宫颈上皮和 其基质肿瘤环境是宫颈癌发生关键。我们将测试具体的假设， 肿瘤微环境有助于宫颈癌的发生。我们还将评估突变在 根据癌症基因组图谱计划获得的见解，宫颈癌发生中的细胞基因， 并确定癌症相关基因的突变，这些突变导致FA患者发生宫颈癌， HPV无关。在第二个目标中，我们将继续利用最近发现的小鼠乳头瘤病毒 MmuPV 1研究高危皮肤HPV在肿瘤性皮肤病中的作用，如患者中所见 与疣状表皮发育不良，使用强大的新的小鼠模型，该疾病在我们的开发， labs.我们还将研究免疫抑制和上皮祖细胞在乳头状瘤病毒中的重要性 诱发皮肤病。