The Lankenau Institute for Medical Research
Strands of DNA encode genetic information that control cancer cellular functions. In cancer therapy, radiation and drugs widely used to treat solid tumors work by damaging the strands of DNA within the cancer cells. However, some cancer cells survive these treatments and develop ways to repair the DNA damage. Additionally, if a tumor is in an environment where there are low levels of oxygen and glucose, the tumor may also be resistant to therapy.
Dr. Ayene is working to enhance cancer therapy using an approach that could be used to treat various types of cancer. Dr. Ayene's group has developed new small molecules that increase the effectiveness of cancer therapy by preventing cancer cells from repairing their DNA in low oxygen and low glucose tumor locations. Currently, they are working to synthesize and test these new compounds to see how well they work in malignant tumor environments. Additionally they are testing a class of molecules called “small interfering RNAs” or siRNAs that interact with tumor RNA to prevent the production of those DNA-repair proteins. Together, these two approaches could be used to maximize the destruction of cancer cells.
Dr. Ayene's laboratory investigates how molecular targeting can be used to increase the therapeutic response of cancer cells to gamma irradiation and chemotherapy. The major focus of his current research is to target functional cysteine molecules in various proteins that are involved in the survival of cancer cells. Dr. Ayene uses novel molecular and biochemical approaches to specifically target Ku70 to inhibit its expression or function, which causes an increased response of cancer cells to gamma irradiation and topoisomerase II inhibitors.
Ku is a heterodimer composed of the Ku70 and Ku86 proteins that is known to play an important role in V(D)J DNA recombination, apoptosis, telomere fusion and double strand break repair. The role of Ku in double strand break repair is relevant to cancer therapy as illustrated by the lack of Ku86 is one of the most etoposide and radiation responsive cell lines that have been studied (XRS5).
In addition to his major goal of sensitizing cancer cells to therapy, Dr Ayene is also interested in elucidating mechanisms of DNA repair, oncogene-mediated resistance to apoptosis, isolation and characterization of cancer stem cells, survival mechanisms of hypoxic cancer cells, and oxidative stress. He is presently the Principal Investigator of the NIH R01 grant “Oxidative Pentose Cycle in Hypoxic Cancer Cell Response” and also serves as a Co-Investigator for the NIH grants “Oxidative damage to DNA Repair Pathways” and “Redox Control of Radiation Response”.
Dr. Ayene's Google Scholar page