Cancer Biology
Clapp, Wade see Blood Cell Development and Genetic Blood Cell Disorders
Cornetta, Ken see Blood Cell Development and Genetic Blood Cell Disorders
Erickson, Leonard, PhD (Pharmacology & Toxicology) Dr. Erickson's laboratory has worked on the mechanisms of action, sensitivity and resistance of DNA damaging antitumor agents, including chloroethylnitrosoureas, the platinum complexes, and the nitrogen mustards. His laboratory was the first to describe the prevention of nitrosourea-induced DNA crosslinks in resistant human tumor cells. The DNA repair enzyme O-6 methylguanine DNSA methyltransferase (MGMT) was subsequently identified and the resistance mechanism repairing initial adducts before the crosslink forms. They have explored biochemical inhibition of MGMT using DNA methylating agents, and most recently a pseudo substrate of the enzyme O-6 benzylguanine, which is currently in clinical trials. They have developed molecular reagents to reverse resistance in tumor cells including anti-MGMT ribozymes, Genetic Suppressor Elements (GSE's), and antisense RNA molecules. Currently, they are exploring the possibility of using MGMT mutants that are resistant to O-6 benzylguanine as gene therapy strategies to protect patients' bone marrow from O-6 benzyguanine toxicity in combination with BCNU treatment of tumors. Click here for more information about Dr. Erickson's work.
Kelley, Mark, PhD (Pediatrics, Pediatric Hematol/Oncol, Wells Center; Biochemistry & Molecular Biology) Dr. Kelley's laboratory studies the DNA repair genes involved in repairing base damage, along with using these DNA repair genes in gene therapy. Ongoing projects include: a) regulation of AP endonuclease (APE/ref-1) in normal and cancer cells; b) use of members of the DNA base excision repair (BER) pathway in protecting cells from the cytotoxic effects of chemotherapeutic alkylating agents and ionizing radiation; c) use of selected BER genes (wild-type or altered in function) in gene therapy to kill tumor cells; d) endogenous and overexpressed oxidative DNA BER genes (Ogg1, NTH, MTH, and MYH) in order to determine which ones may be involved in mitotic and postmitotic oxidative DNA repair (oxidative DNA damage has been implicated in a variety of diseases, aging, neurological defects, and cancer; additionally, a number of cancer chemotherapeutic agents produce oxidative DNA damage). Click here for more information about Dr. Kelley's work.
Lee, Suk Hee, PhD (Biochemistry & Molecular Biology) DNA damage due to irradiation or chemicals must be repaired to prevent genomic alterations that could otherwise give rise to cancer. Dr. Lee's laboratory's long-term objective is to understand the molecular mechanism of how cells respond to DNA damage. To meet this objective, their research focuses on 1) recognizing DNA damage in mammals and the following DNA repair process, 2) defining the molecular mechanism of damage-induced replication arrest, and 3) identifying and characterizing genes involved in DNA damage-signaling pathway. Click here for more information about Dr. Lee's work.
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