The research group, under the direction of Dr. Gayathri Devi, focuses on translational and clinical applications of programmed cell death signaling. Cell death is a critical process in tissue sculpting, adult cell homeostasis, for destruction of damaged cells and in pathobiology. We are, in particular, interested in elucidating molecular mechanisms of stress-induced cell survival/death signaling in normal and cancer cells and how this process regulates immune response.
Our work has identified the dominant role of a class of anti-cell death proteins called Inhibitor of Apoptosis Proteins (IAPs) in cancer cell survival and during development of acquired resistance to extrinsic and intrinsic death signals. Current funded research projects in the lab focus on innovative approaches toward immunosuppressive minimization, in vitro and in vivo tumor biology models, novel approaches toward islet xenotransplantation, and innovative preclinical models and strategies to modulate this anti-cell death.
Dr. Devi has also established a special research program to study inflammatory breast cancer (IBC), designated a rare and distinct type of breast cancer and a cancer health disparity by the National Cancer Institute (NCI).
Dr. Devi is an American Cancer Society Research Scholar Grant Awardee from Duke University. Prior to joining Duke, she received training in both academic research in the area of growth factor receptor signaling at Oregon Health and Sciences University, and in the biotechnology sector at AVI BioPharma, Inc. in the area of genomics-based anti-cancer drug development.
Key Projects Underway
- XIAP-NFκB tumor cell signaling in evasion of immune-mediated cell death
- Development of novel preclinical models/assays to study tumor emboli, dermal invasion, and lymphatic dissemination
- Understanding stromal tumor cell tropism and the development of nanotheranostics for inflammatory breast cancer therapy
- Molecular mechanisms of health disparities in inflammatory breast cancer; screening strategies and repurposing drugs to improve standard of care of locally advanced breast cancer
- Characterization of ToxCast environmental chemical library in anti-cancer therapeutic resistance
- Elucidating cell death mechanisms limiting xenotransplantation and defining strategies to improve islet survival
- Development of a program in multidisciplinary education and research in translational sciences (Duke MERITS)
Recent research highlights include the development of a novel redox modulation approach for breast cancer therapy. We have identified an adaptive stress-response signaling pathway (characterized by NFkB transcriptional signature) in locally advanced tumors, including inflammatory breast cancer. This finding has led to the discovery of the use of the FDA-approved drug disulfiram (DSF) when combined with copper to target pNFkB, cancer stem-like cells, and to increase tumor cell kill. These results were published in the Molecular Oncology Journal, 2015 (PMID: 25769405). The current goal of the collaborative team is to extend this to breast cancer clinical trials.
Our body of work has identified the central role of the X-linked inhibitor of apoptosis protein (XIAP) in adaptive stress-response signaling, which leads to both de novo and acquired resistance to cell death stimuli. In recently completed studies published in the Cell Death and Disease Journal (PMID: 26821068), we have discovered that XIAP expression can cause immunosuppression and is a critical modulator of responses to antibody-dependent cellular cytotoxity in cancer cells. We are developing strategies to target the effects of XIAP on the activation of caspases and pNFkB and the suppression of reactive oxygen species to enhance the activity of immunotherapy, chemotherapy, and EGFR/HER2-targeted drugs.
- Devi Interview for her laboratory’s work on repurposing an anti-alcoholism drug for IBC therapy. WRAL June 10, 2015
- Dr. Devi was featured in the Women in STEM. Research Highlight and Interview for Women in Stem, Academic Minute, WAMC NPR affiliate, August 2015
- Dr. Devi – Era of Hope Investigator Highlight presentation
- BPA May Make Breast Cancer Cells Resistant To Treatment. WUNC, June 24, 2014
Research opportunities available for undergrads, med students, PhD candidates, etc.
Gayathri Devi, PhD