研究的焦点

我们的实验室专注于DNA损伤及其修复对人类健康结果之间的相互关系，主要是癌症和其他与年龄有关的疾病的发展。其中一个重点领域是维持基因组稳定性所需的人类RecQ解旋酶的功能。尽管有五种人类RecQ解旋酶，我们主要研究的是WRN和BLM分别在过早衰老和癌症易发遗传疾病Werner和Bloom综合征中缺失的作用。我们和其他人的研究结果表明，WRN和BLM在端粒维持和DNA重组途径中起作用;这些途径的缺陷导致1)染色体不稳定，增加癌症易感性;2)细胞衰老和凋亡细胞死亡，加速某些组织特异性衰老表型。虽然WRN对端粒稳定性有一定的影响，但目前认为WRN和BLM也参与了细胞妥善化解DNA损伤等情况引起的复制应激的能力。我们的研究重点是阐明WRN和BLM在各自途径中的具体功能。我们还对靶向这些途径感兴趣，以潜在地增强某些破坏DNA的癌症化疗药物的疗效。最近的另一个研究领域是调查暴露于特定环境因子在增加癌症易感性方面所起的作用。我们的实验室对金属和烟草相关暴露对肺癌和其他癌症DNA损伤产生和修复的影响特别感兴趣。 This includes examination of 1) generation of DNA damage and/or alteration of DNA repair efficiency by specific compounds or complex mixtures, 2) differential repair efficiency of structurally distinct DNA lesions, and 3) relationships between environmental exposures, steady-state DNA damage burdens and cancer development. To this end, our lab has developed assays suitable for measuring and quantifying a broad spectrum of lesions (or subsets thereof) in DNA derived from experimental, clinical, and epidemiological samples. In collaborations with other researchers here at the University of Kentucky and elsewhere, we are implementing these assays in several scenarios related to cancer susceptibility. A significant portion of this research is centered on possible additional contributing factors that underlie the extremely high incidence of smoking-related lung cancer in Appalachian Kentucky.

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