Nicholas Wallace

Dr. Wallace has studied how alterations in cell signaling contribute to genome instability and cancer for more than twenty years. His graduate training with Prescott Deininger focused on how changes in cellular signaling environments increase the risk that human mobile elements induce carcinogenic mutations. During his postdoctoral work with Denise Galloway, he investigated how human papillomavirus (HPV) oncogenes promote tumorigenesis by disrupting tumor suppressor pathways, including DNA repair, apoptotic signaling, and cell cycle control. These experiences laid the foundation for his independent research program at Kansas State University, where his laboratory examines HPV oncogene-induced dysregulation of cell signaling in cancer. His group's early work demonstrated that oncogenes from cutaneous HPVs compromise genome maintenance by disrupting mitosis, increasing ultraviolet radiation-induced DNA damage, and suppressing high-fidelity DNA repair pathways. These defects force cells to rely on highly mutagenic repair mechanisms, increasing mutation risk by more than forty-fold and providing a mechanistic explanation for the elevated cancer risk associated with cutaneous HPV infections in immunocompromised individuals. Over the past seven years, Dr. Wallace has extended this work to high-risk HPVs, which cause approximately 600,000 cases of cervical cancer annually. His laboratory has shown that high-risk HPV oncogenes increase the abundance of DNA repair factors while mislocalizing the repair machinery away from DNA lesions, driving reliance on the error-�prone pathway microhomology-mediated end joining (MMEJ). His ongoing NIH R21 award is testing whether MMEJ dependence promotes mutational accumulation in cervical cancer and whether inhibition of this pathway selectively sensitizes tumor cells to DNA-damaging therapies. In parallel, his group has demonstrated that HPV oncogenes impair translesion synthesis, increasing sensitivity to cisplatin while restoration of this pathway confers drug resistance. Collectively, this work defines how HPV-driven alterations in cell signaling reprogram DNA damage responses to promote genome instability and therapeutic vulnerability.