Shyamal D. Desai , PhD
The goal of our research is to develop novel clinical treatments for cancers and neurodegeneration associated with Ataxia Telangiectasia (A-T), a debilitating hereditary childhood neurodegenerative disease. This line of research is particularly important as metastasis is still a major clinical problem in cancer treatment, and to date there is no cure or preventive medicines available for treating A-T.
Our research is based on my seminal findings as an Assistant Professor at UMDNJ that elevated levels of a ubiquitin-like protein ISG15 (Interferon-Stimulated Gene 15) inhibit the canonical ubiquitin pathway, a key regulator of vital cellular processes, in cancer. This past research focused on identifying the cellular factors responsible for determining the sensitivity of cancer cells to camptothecin, an anticancer drug used in clinic to manage cancers. Of particular interest, we found ISG15, an antagonist of the ubiquitin pathway, is an important determinant of camptothecin sensitivity in tumor cells. Based on these findings, we proposed that ISG15 and factors in its conjugation pathway could serve as tumor biomarkers for CPT sensitivity/resistance in cancer patients. A phase II clinical trial of camptothecin for patients with non-small cell lung cancer and high ISG15 expression has been initiated in August, 2012 (Clinical Trials-Government Identifier # NCT01607554). This is an important leap forward as our research has now moved into clinic. Our current cancer research will reinforce and extend the importance of ISG15 in cancer prevention and treatment in clinic.
In addition to our ongoing work on ISG15 and cancer, my group at LSU has also established that ISG15 is elevated and inhibits the ubiquitin pathway in human A-T cells. Because ISG15 inhibits the ubiquitin pathway, and lesions in the ubiquitin pathway lead to neurodegeneration, understanding the cellular and molecular principles that underpin ISG15’s role in A-T neurodegeneration has become an important research priority in my lab. We are currently exploring the role of ISG15 in the etiology of cancer and A-T neurodegeneration using cell culture, mouse, and human disease models that are developed in our lab at LSU. Our results will provide a new paradigm for cancer prevention and treatment, and reveal a novel role of the “ISG15 proteinopathy” in A-T neurodegeneration.