Danuta Kozbor

I am a basic scientist with expertise in pre-clinical studies specializing in novel immunotherapeutic approaches to target the suppressive tumor microenvironment (TME) in platinum resistant cancers. The overall goal of my research is to elucidate the molecular and cellular mechanisms of antitumor innate and adaptive immune responses induced by oncolytic viral vectors in metastatic tumors, focusing primarily on ovarian and breast cancers. I have designed novel approaches to enhance antitumor efficacy of oncolytic virotherapy by: i) expressing therapeutic genes, such as a CXCR4 antagonist to target the CXCL12/CXCR4 signaling axis in the TME; ii) augmenting spread of the virus within tumors by inducing changes in the tumor vasculature; and iii) exploring combination therapies using agents with both cytotoxic and immunomodulatory effects in the TME. These research activities have been supported by a multi-investigator and multi-institutional NCI Cancer Moonshot U01 grant, SPORE grant and recently completed an investigator-initiated research award from Department of Defense and a R03 grant from NCI. As part of the CCSG effort, and in collaboration with Dr. Kunle Odunsi, we are analyzing the mechanisms by which oncolytic virotherapy with the CXCR4 antagonist (OVV-CXCR4-A-Fc) and PD1/PDL1 blockade overcome the vascular endothelial barrier to promote intratumoral T cell trafficking and accumulation. The OVV-CXCR4-A-Fc construct has been developed in my laboratory. Toxicology studies are carried out in response to the FDA request and as a part of the pending Investigational New Drug (IND) application for the use of OVV-CXCR4-A in clinical trials. I am also committed to providing quality training in the development of future leaders in scientific and translational research. For the past twenty years, I have been involved in numerous activities of the Graduate Program within the Department of Immunology at Roswell Park. This includes i) serving on Thesis/Dissertation Committees for Master and PhD students, ii) serving as a director of the Advanced Topics in Immunology course for PhD students, iii) presenting lectures to graduate students, iv) serving as Chair of Qualifying Exam Committee, v) participating in admissions review process, vi) supervising pre- and post-doctoral trainees, and vii) supervising rotation and summer students. As a postdoctoral fellow at the Wistar Institute in Philadelphia, PA, I gained experience in molecular genetics during the research on the mechanisms of oncogene activation in human tumors by chromosomal translocation. Subsequently, as an independent investigator, I expanded my research to virology by analyzing the effect of perinatal HIV infection on disease progression, and induction of HIV-specific immune responses using a recombinant vaccinia virus as a vector for AIDS vaccine delivery. As PI or Co-Investigator on several previous NIH- and institute-funded grants, I laid the background for the proposed research by developing oncolytic vaccinia viruses expressing mimotopes of tumor associated antigens and by targeting the antigens to the activating Fc gamma receptor on dendritic cells. In addition, I successfully administered the projects (e.g. staffing and budget), collaborated with other researchers, and produced several peer-reviewed publications from each project. I am aware of the importance of frequent communication among project members and constructing a realistic research plan, timeline and budget.