Ji Luo, Ph.D., focuses on understanding the biology of cancers with mutations in the KRAS oncogene. Current studies are focusing on two rare genetic diseases: xeroderma pigmentosum (XP) a cancer-prone genetic disease with cellular hypersensitivity to ultraviolet radiation (UV) and defective DNA repair and trichothiodystrophy (TTD) a disorder with developmental abnormalities and defects in some of the same genes as XP without increased cancer risk.The long-term goals are to: 1) define the molecular defects in these diseases, 2) characterize their clinical abnormalities and extent of phenotypic heterogeneity, 3) correlate the molecular defects with clinical abnormalities, 4) assess the altered molecular function, 5) identify and characterize the underlying mechanisms (pathophysiology) and how they lead to clinical disease, and 6) influence these processes by exploring methods of cancer prevention. The approach involves integrated clinical, molecular, and translational investigations of disorders with defective DNA repair. Kenneth Kraemer, M.D., investigates the role of DNA repair in prevention of cancer and in human development. Kent Hunter, Ph.D., is a pioneer in systems genetics, having demonstrated first in mouse models, and confirming by association studies in cancer patients, that an individual's genetic background has a significant effect on the propensity of their tumors to metastasize his work has established a new paradigm of inherited susceptibility in metastasis research. Jing Huang, Ph.D., has focused his research program on the epigenetic mechanisms underlying cancer and stem cells, has used genomics to uncover a role for the tumor suppressor p53 in regulating the differentiation of embryonic stem cells during DNA damage. His work has shed new light on how cells make the decision to proliferate and the origin of cell-to-cell heterogeneity. In particular, he applies state-of-the-art live-cell imaging approaches and fluorescent biosensors to dissect the dynamic signaling pathways controlling the G1 to S phase transition. Steven Cappell, Ph.D., focuses on understanding the cellular and molecular mechanisms underlying cell cycle regulation at the single-cell level.
The research focus of the LCBG principal investigators is as follows: The LCBG operates a novel University-NCI graduate partnership research training program in comparative molecular pathology, including both Ph.D. Emanating from our studies are new therapeutic combinations for targeted cancers now in clinical trials. The LCBG also develops and correlates novel protocols in molecular diagnostics for human and animal tissues, and in noninvasive medical imaging for animal models. Studies are performed in vivo in animal models, in vitro in cell and organ culture, and on tissues and cells obtained from human volunteers and cancer patients.
These investigators conduct a well integrated research program consisting of basic and translational components that are designed to: elucidate the cellular and tissue changes associated with specific stages of carcinogenesis, detect and characterize genetic modifiers fundamental to cancer susceptibility and progression, define the molecular mechanisms involved in the pathogenesis of major human cancers, and develop rational approaches for cancer prevention and treatment. The LCBG currently encompasses the work of 12 principal investigators supervising independent research programs with highly overlapping experimental goals and approaches. The Laboratory of Cancer Biology and Genetics (LCBG) self-assembled in 2006 through the merger of the Laboratory of Cellular Carcinogenesis and Tumor Promotion (LCCTP), the Laboratory of Cell Regulation and Carcinogenesis (LCRC) and the Laboratory of Genetics (LG).
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