Iraimoudi (Ira) S. Ayene, PhD

Photo of Iraimoudi (Ira) Ayene

Email:  AyeneI@mlhs.org

Phone: 484.476.8183

Fax: 484.476.8533

Office: R228

Department: Faculty

Association: Resident Faculty

Education

  • M.Sc., Life Sciences, Jawaharlal Nehru University, New Delhi, India, 1980
  • Ph.D., Biology, Chemistry, & Radiation Biology, Jawaharlal Nehru University, New Delhi, India, 1986

Current Appointments

  • 2007 to Present: Associate Professor, Lankenau Institute for Medical Research

Research Interest(s)

  • Improving the effectiveness of radiation and chemotherapy for cancer patients
  • Google Scholar page

Lay Description:


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.

Scientific Description:


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

Selected Publications:

  1. Li J, Ward KM, Zhang D, Dayanandam E, DeNittis AS, Prendergast GC, Ayene IS: A bioactive probe of the oxidative pentose phosphate cycle: Novel strategy to reverse radioresistance in glucose deprived human colon cancer cells. Toxicol. in Vitro, Aug 16, 2012 [Epub ahead of print]. http://dx.doi.org/10.1016/j.tiv.2012.08.012
  2. Li J, Zhang D, Ward KM, Prendergast GC, Ayene IS: Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro. Toxicol. in Vitro, Jun 26: 603-612, 2012, Epub Jan 31, 2012.
  3. Li J, Ayene R, Ward KM, Dayanandam E and Ayene IS: Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells. Cell Biochem. Funct., 27: 93-101, 2009.
  4. Ayene IS, Biaglow JE, Kachur AV, Stamato TD and Koch CJ: Mutation in G6PD gene leads to loss of cellular control of protein glutathionylation: Mechanism and Implication. J. Cell. Biochem., 103, 123-135, 2008.
  5. Tuttle SW, Maity, A, Oprysko PR, Kachur AV, Ayene IS, Biaglow JE, and Koch CJ: Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration: Implications for the mechanism of HIF-1a stabilization under moderate hypoxia. J. Biol. Chem., 282, 36790-36796, 2007.
  6. Ayene IS, Koch CJ and Krisch RE: DNA strand breakage by bivalent metal ions and ionizing radiation. Int. J. Radiat. Biol., 83, 195-210, 2007. 
  7. Biaglow JE, Ayene IS, Tuttle SW, Koch CJ, Donahue J and Mieyal JJ: Role of Vicinal Protein Thiols in Radiation and Cytotoxic Responses. Radiat. Res. 165, 307–317, 2006. 
  8. Ayene IS, Ford LP and Koch CJ: Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and ? radiation. Mol. Cancer Ther. 4(4), 529-536, 2005. 
  9. Biaglow JE, Ayene IS, Koch CJ, Donahue J, Stamato TD, Mieyal JJ and Tuttle SW: Radiation response of cells during altered protein thiol redox. Radiat. Res., 159, 484-494, 2003. 
  10. Ayene IS, Stamato TD, Mauldin SK, Biaglow JE, Tuttle SW, Jenkins SF and Koch CJ: Mutation in the glucose-6-phosphate dehydrogenase gene leads to inactivation of Ku DNA end binding during oxidative stress. J. Biol. Chem., 277, 9929-9935, 2002. 
  11. Ayene IS, Koch CJ, Tuttle SW, Stamato T, Perez ML and Biaglow JE: Oxidation of cellular thiols by hydroxyethyldisulfide inhibits DNA double strand break rejoining in G6PD deficient mammalian cells. Int. J. Radiat. Biol. 76, 1523-1531, 2000. 
  12. Biaglow JE, Ayene IS, Koch CJ, Donahue J, Stamato T and Tuttle SW: G6PD deficient cells and the bioreduction of disulfides: Effects of DHEA, GSH depletion and phenylarsine oxide. Biochim. Biophys. Res. Comm. 273, 846-852, 2000. 
  13. Ayene IS, Bernhard EJ, Muschel RJ, McKenna WG, Krisch RE and Koch CJ: DNA as an important target in radiation induced apoptosis of myc and myc plus ras oncogene transfected cells. Int. J. Radiat. Biol., 76, 343-355, 2000. 
  14. Biaglow JE, Koch CJ, Tuttle S, Manevich Y, Ayene IS, Bernhard EJ, McKenna WG, and Kachur A: The measurement of bioreductive capacity of tumor cells using methylene blue. Int. J. Radiat. Oncol. Biol. Phys., 42, 769-773, 1998. 
  15. Zhao G, Ayene IS and Fisher AB: Role of iron in ischemia reperfusion oxidative injury of rat lungs. Am. J. Respir. Cell Mol. Biol. 16: 293-299, 1997. 
  16. Ayene IS, Koch CJ, and Krisch RE: Simulation of the cellular oxygen effect with an in vitro model system using DNA strand breaks as an endpoint. Radiat. Res. 146: 501-509, 1996. 
  17. Ayene IS, Koch CJ, and Krisch RE: Modification of radiation-induced strand breaks by glutathione: Comparison of single and double strand breaks in SV40 DNA. Radiat. Res. 144: 1-8, 1995. 
  18. Ayene IS, Koch CJ and Krisch RE: Role of scavenger derived radicals in the induction of double strand and single strand breaks in irradiated DNA. Radiat. Res. 142: 133-143, 1995. 
  19. Krisch RE, Ayene IS, Koch CJ: Interaction of Thiol and Non-Thiol Scavengers in the Modification of Radiation-Induced DNA Damage. In: Radiation Damage in DNA: Structure/Function Relationships at Early Times. (Fuciarelli, AF, & Zimbrick, JD, Eds.), Battelle Press, Ohio, pp. 383-391, 1995. 
  20. Fisher AB, Dodia C, Ayene IS and Al-Mehdi A: Ischemia/reperfusion injury to the lung. Cellular, Biochemical, and Molecular Aspects of Reperfusion Injury. Annals of the New York Academy of Sciences, 723: 197-207, 1994. Ayene IS, Al-Mehdi A, and Fisher AB: Inhibition of lung tissue oxidation during ischemia/reperfusion injury by 2-mercaptopropionylglycine. Arch. Biochem. Biophys., 303: 307-312, 1993.
  21. Ayene IS, Dodia C and Fisher AB: Role of oxygen in oxidation of lipid and protein during ischemia/reperfusion in isolated perfused rat lung. Arch. Biochem. Biophys., 296: 183-189, 1992. 
  22. Fisher AB, Dodia C, Tan Z, Ayene IS and Eckenhoff RG: Oxygen-Dependent Lipid Peroxidation during lung Ischemia. J. Clin. Invest., 88: 674-679, 1991. 
  23. Webster L, Zhang K, Chance B, Ayene IS, Culp JS, Huang WJ, Wu FYH and Ricciardi RP: Conversion of a functional C4 Zinc Finger to a nonfunctional H2C2 Zinc finger: an X-ray absorption study. Proc. Nat. Acad. Sci., U.S.A. 88: 9989-9993, 1991. 
  24. Zhang K , Chance B , Reddy KS, Ayene IS , Stern EA and Bunker G: Structural differences in solution and crystalline forms of met-myoglobin. Biochemistry, 30, 9116-9120, 1991. 
 
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