NIH Grants: K08
Dr. Coffman is a physician-scientist actively conducting laboratory-based and translational research and maintaining a specialized clinical practice focused on the medical treatment of ovarian cancer.
Dr. Coffman’s research focuses on understanding and targeting the cancer-supporting stromal tissues which are critical to the survival, growth, and spread of ovarian cancer. Specifically, Dr, Coffman’s lab studies a critical non-malignant component of the ovarian cancer microenvironment, the carcinoma-associated mesenchymal stem cell (CA-MSC). CA-MSCs are stromal progenitor cells that significantly increase cancer growth, enrich the cancer stem cell pool and increase chemotherapy resistance. The lab studies how CA-MSCs are formed and develop tumor-supporting properties. The lab also focuses on identifying important tumor cell:CA-MSC interactions which mediate CA-MSC’s pro-tumorigenic functions and have the potential for translation into new therapeutic targets. Additionally, the lab studies the role of the tumor microenvironment in ovarian cancer metastasis. New evidence demonstrates high-grade serous ovarian cancer, the most common and deadly form of ovarian cancer, likely arises in the fallopian tube and the ovary is a critical initial site of metastasis. The Coffman lab developed three novel mouse models of ovarian cancer metastasis which demonstrate ovarian cancer is capable of hematogenous spread with a unique tropism for the ovary. Further, initial metastasis to the ovary appears to be critical for the development of intra-abdominal metastasis implicating unique aspects of the ovary microenvironment in propagating metastasis. How CA-MSCs impact the development of ovarian cancer metastasis and the metastatic microenvironment is an active area of investigation. The ultimate goal of this research is to translate novel laboratory findings into powerful therapeutic approaches for the prevention and treatment of ovarian cancer.
- Coffman L, Mooney C, Lim J, Bai S, Silva I, Gong Y, Yang K, Buckanovich RJ: Endothelin receptor-A is required for the recruitment of antitumor T cells and modulates chemotherapy induction of cancer stem cells. Cancer Biol Ther 14(2): 184-92, 2013.PM23192269/PMC3572000
- Choi YJ, Ingram PN, Yang K, Coffman L, Iyengar M, Bai S, Thomas DG, Yoon E, Buckanovich RJ: Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2. Proc Natl Acad Sci U S A 112(50): E6882-8, 2015.PM26621735/PMC4687560
- Coffman LG, Burgos-Ojeda D, Wu R, Cho K, Bai S, Buckanovich RJ: New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination. Transl Res 175: 92-102, 2016. PM27083386/PMC5003680
- Coffman LG, Choi YJ, McLean K, Allen BL, di Magliano MP, Buckanovich RJ: Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop. Oncotarget 7(6): 6916-32, 2016. PM26755648/PMC4872758
- Iyengar, M, O’Hayer, P, Cole, A, Sebastian, T, Yang, K, Coffman, L*, Buckanovich, R* (*co-last author): CDK4/6 inhibition as maintenance and combination therapy for high grade serous ovarian cancer. Oncotarget 9(21):15658-15672, 2018. PM29644000/PMCPMC5884655
- McLean, K, Tan, L, Bolland, D, Coffman, L, Peterson, L, Talpaz, M, Neamati, N, Buckanovich, R. Leukemia Inhibitory Factor Functions in Parallel with Interleukin-6 to Promote Ovarian Cancer Growth. Oncogene. Oct 2018. PM30305729
- Coffman, L, Pearson, A, Frisbie, L, Freeman, Z, Christie, E, Bowtell, D, Buckanovich, R. Ovarian carcinoma-associated mesenchymal stem cells arise from tissue-specific normal stroma. Stem Cells. Oct 2018.PM30353617