Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Neurosurgery
Secondary Appointment(s):
Physiology, Surgery
Administrative Title:
Director, Research and Discovery in Neurosurgery -and- Co-Director, Translational Therapeutics Research Group
Location:
800 West Baltimore St. Biopark Building 1, #320
Phone (Primary):
410-706-8172
Fax:
410-706-8234
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
Highlighted Publications
Hersh, D.S., Peng, S., Dancy, J.D., Galisteo, R., Eschbacher, J.M., Castellani, R.J., Heath, J.E., Legesse, T., Kim, A.J., Woodworth, G.F., Tran, N.L. and Winkles, J.A. (2018). Differential expression of the TWEAK receptor Fn14 in IDH1 wild-type and mutant gliomas. Journal of Neuro-Oncology 138:241-250.
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.
Dancy, J.G., Wadajkar, A.S., Connolly, N.P., Galisteo, R., Ames, H.M., Peng, S., Tran, N.L., Goloubeva, O.G., Woodworth, G.F., Winkles, J.A. and Kim, A.J. (2020). Decreased non-specific adhesivity, receptor-targeted (DART) therapeutic nanoparticles for primary and metastatic breast cancer. Science Advances 6:eaax3931.
Connolly, N.P., Galisteo, R., Xu, S., Bar, E.E., Peng, S., Tran, N.L., Ames, H.M., Kim, A.J., Woodworth, G.F. and Winkles, J.A. (2021). Elevated fibroblast growth factor-inducible 14 expression transforms proneural-like gliomas into more aggressive and lethal brain cancer. Glia 69:2199-2214.
Carney, C.P., Kapur, A., Anastasiadis, P., Ritzel, R.M., Chen, C., Woodworth, G.F., Winkles, J.A. and Kim, A.J. (2023). Fn14-directed DART nanoparticles selectively target neoplastic cells in preclinical models of triple negative breast cancer brain metastasis. Molecular Pharmaceutics 20:314-330.
Carney, C.P., Pandey, N., Kapur, A., Saadi, H., Ong, H.L., Chen, C., Winkles, J.A., Woodworth, G.F. and Kim, A.J. (2023). Impact of targeting moiety type and protein corona formation on the uptake of Fn14-targeted nanoparticles by cancer cells. ACS Nano 17:19667-19684.
Research Interests
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