Acting Director, Research and Discovery in Neurosurgery -and- Co-Director, Translational Therapeutics Research Group
800 West Baltimore St. Biopark Building 1, #320
Education and Training
- Undergraduate Degree: B.A., Biology, University of Delaware, 1977
- Graduate Degree: Ph.D., Biology, University of Virginia, 1983
- Postdoctoral Fellowship: National Institutes of Health, 1983-1986
Winkles, J.A. (2008). The TWEAK-Fn14 cytokine-receptor axis: Discovery, biology, and therapeutic targeting. Nature Reviews Drug Discovery 7:411-425.
Asrani, K., Keri R.A., Galisteo, R., Brown, S.A.N., Morgan, S.J., Ghosh, A., Tran, N.L. and Winkles, J.A. (2013). The HER2- and heregulin-1 (HRG)-inducible TNFR superfamily member Fn14 promotes HRG-driven breast cancer cell migration, invasion and MMP9 expression. Molecular Cancer Research 11:393-404.
Cheng, E., Armstrong, C.L., Galisteo, R. and Winkles, J.A. (2013). TWEAK/Fn14 axis-targeted therapeutics: Moving basic science discoveries to the clinic. Frontiers in Immunology 4:473.
Zhou, H., Mohamedali, K.A., Gonzalez-Angulo, A.M., Cao, Y., Migliorini, M., Cheung, L.H., LoBello, J., Lei, X., Qi, Y., Hittelman, W.N., Winkles, J.A., Tran, N.L. and Rosenblum, M.G. (2014). Development of human serine protease-based therapeutics targeting Fn14 and identification of Fn14 as a new target overexpressed in TNBC. Molecular Cancer Therapeutics 13:2688-2705.
Cheng, E., Whitsett, T.G., Tran, N.L. and Winkles, J.A. (2015). The TWEAK receptor Fn14 is an Src-inducible protein and a positive regulator of Src-driven cell invasion. Molecular Cancer Research 13: 575-583.
Perez, J.G., Tran, N.L., Rosenblum, M.G., Schneider, C.S., Connolly, N.P., Kim, A.J., Woodworth, G.F. and Winkles, J.A. (2016). The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics. Oncogene 35:2145-2155.
Connolly, N.P., Stokum, J.A., Schneider, C.S., Ozawa, T., Xu, S., Galisteo, R. Castellani, R.J., Kim, A.J., Simard, M., Winkles, J.A., Holland, E.C. and Woodworth, G.F. (2017). Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer. PLoS One 12:e0174557.
Wadajkar, A.S., Dancy, J.G., Roberts, N.B., Connolly, N.P., Strickland, D.K., Winkles, J.A., Woodworth, G.F. and Kim, A.J. (2017). Decreased non-specific adhesivity, receptor-targeted (DART) nanoparticles exhibit improved dispersion, cellular uptake, and tumor retention in invasive gliomas. Journal of Controlled Release 267:144-153.
Hersh, D.S., Harder, B.J., Roos, A., Peng, S., Heath, J.E., Legesse, T., Kim, A.J., Woodworth, G.F., Tran, N.L. and Winkles, J.A. (2018). The TNF receptor family member Fn14 is highly expressed in recurrent glioblastoma (GBM) and in GBM patient-derived xenografts with acquired temozolomide resistance. Neuro-Oncology 20:1321-1330.
The major project in my laboratory is focused on elucidating the biological properties of TWEAK, a member of the TNF superfamily of structurally-related proteins, and its sole signaling receptor (Fn14), in human cancer. TWEAK:Fn14 engagement in cancer cells stimulates multiple signal transduction pathways, including the NF-kB pathway, and this can trigger various cellular responses (e.g., growth, migration, invasion). There is also evidence that Fn14 signaling may play a role in cancer cell sensitivity to radiation and chemotherapy. Our group and others have shown that Fn14 is expressed at low levels in most normal tissues but overexpressed in many solid primary tumor types and in metastatic lesions; thus, Fn14 is an attractive cell surface portal for cancer drug delivery. Our present research efforts can be categorized as follows:
- TWEAK and Fn14 structure/function studies; analysis of TWEAK and Fn14 gene regulation and Fn14 signaling mechanisms
- Determine the role of the TWEAK/Fn14 axis in cancer biology, with particular focus on the regulation of cancer cell invasion and metastasis
- Pre-clinical development of Fn14-targeted, drug-loaded nanotherapeutics for cancer patients