Cancer Research: DNA Repair and Breast Cancer

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Publications and Presentations

  1. Zhong, X., Hoelz, D.J., Kumar, H.R., Sandoval, J.A., Rescorla, F.J., Hickey, R.J., and Malkas, L.H. (2009). Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma. Pediatr Blood Cancer 53, 332-337.
  2. Turner, K.E., Kumar, H.R., Hoelz, D.J., Zhong, X., Rescorla, F.J., Hickey, R.J., Malkas, L.H., and Sandoval, J.A. (2009). Proteomic Analysis of Neuroblastoma Microenvironment: Effect of the Host-Tumor Interaction on Disease Progression. J Surg Res. [e-pub ahead of print; PMID: 19592021]

Primary Investigator: Derek Hoelz, Ph.D.

Genetic mutations can arise through exposure to a variety of agents including environmental carcinogens such as arsenic, dioxin, and radon. Mutations arise as a result of DNA damage, which can occur through a variety of means. Mutations ultimately enable the cell to grow into tumors, invade surrounding tissues, and metastasize to distant sites in the body. In cells, DNA is packaged into structures called chromatin, and the chromatin structure is controlled by a group of enzymes called HDACs. Drugs that inhibit HDACs show promise in the treatment of multiple cancers. Our laboratory is interested in how environmental pollutants such as arsenic affect HDAC activity and how this differs from the anticancer activities of the HDAC inhibitors.

Another new therapeutic used to treat cancers inhibits another enzyme involved in the detection of DNA damage, PARP. PARP inhibitors have also been approved for the treatment of multiple cancers, and PARP’s activity is altered in cells following exposure to arsenic and dioxin. We are currently investigating alterations to PARP and their effects on DNA damage, mutagenesis, and cancer cell growth. In addition to studying HDAC and PARP, our laboratory has also identified a new gene in human cells.

This gene encodes an enzyme similarly to HDAC and PARP, which we named ARM1. ARM1 possesses an activity never before observed in human cells and appears to be involved in cellular growth following DNA damage. We are currently working to further define and characterize ARM1’s functions and hope to eventually identify new therapeutic approaches for the treatment of human cancers.