Jennifer Isaacs, PhD
Co-Director, Graduate Program
Graduate Coordinator, Pharmacology MS Program
Member, Developmental Cancer Therapeutics Program
1997 Ph.D., University of North Carolina Chapel Hill
Office: HO 712E
Understanding how tumors progress and metastasize, the contribution of tumor-stromal communication, and evaluation of therapeutics
Tumor progression, epithelial to mesenchymal transition (EMT), cell polarity, eHsp90, microRNAs, epigenetics, signal transduction, tumor microenvironment, prostate cancer, glioblastoma (GBM)
The research in my lab is focused upon understanding factors that contribute to the spread of solid tumors. Tumor metastasis is responsible for 90% of all cancer deaths. In order for tumors to metastasize, they must acquire new properties, such as the ability to invade host tissue and colonize distant sites. During cell invasion, tumor cells typically exhibit cytoskeletal changes that allow them to loosen their cell-cell contacts and move through tissues. These changes in cell shape are key initiating events in the invasion-metastasis cascade. As cells continue to undergo these changes in cell shape, they may activate the epithelial to mesenchymal transition (EMT) genetic program, which further drives cancer aggressiveness.
Although the genes involved in EMT are well known, the tumor-derived factors initiating this process are not as clearly defined. We are studying a new tumor-secreted factor called extracellular heat shock protein 90 (eHsp90). Tumor eHsp90 has been shown to stimulate cancer cell motility and invasion, and we have recently published that eHsp90 can initiate EMT events in prostate cancer cells (Hance MW et al., JBC 2012). Importantly, we also showed that more aggressive prostate cancer cell lines secrete more eHsp90, indicating that eHsp90 plays an important role in tumor progression. A number of reports also document eHsp90 in patient samples, supporting a clinical role for this protein. We are now working to decipher how eHsp90 regulates tumor cell signaling and coordinates genetic and epigenetic events to promote changes in cell shape that support tumor dissemination.
Overall, our findings have validated that eHsp90 is a promising therapeutic target in cancer. As such, we will be evaluating the therapeutic potential of compounds designed to target eHsp90. Our ultimate goal is to translate our findings towards the identification of novel approaches to minimize the spread of locally advanced cancers and to decrease the robustness of later stage malignancies. A complementary goal is to identify genetic and epigenetic events driving early tumor progression, as these effectors may also serve as biomarkers to identify at risk patients at earlier disease stages. We utilize a diverse array of molecular biology techniques to answer our complex questions, and we also collaborate with several groups with particular expertise, thereby allowing us to expand the scope of our questions.
Please visit our lab webpage to learn more about our ongoing projects, my mentoring approach, and positions available.
1. Krystal D. Nolan, Omar E. Franco, Michael W. Hance, Simon W. Hayward, and Jennifer S. Isaacs. Tumor secreted Hsp90 subverts Polycomb function to drive prostate tumor growth and invasion. Journal of Biological Chemistry. 2015 Feb 10; Epub ahead of print.
2. Bohonowych JE, Hance MW, Nolan KD, Defee M, Parsons CH, Isaacs JS. Extracellular Hsp90 mediates an NF-κB dependent stromal inflammatory program: Implications for the tumor microenvironment. /Prostate/. 2014 74(4):395-407.
3. Hance MW, Dole K, Gopal U, Bohonowych JE, Jezierska-Drutel A, Neumann CA, Liu H, Garraway IP, Isaacs JS. Secreted Hsp90 is a novel regulator of the epithelial to mesenchymal transition (EMT) in prostate cancer. J Biol Chem. 2012 Nov 2;287(45):37732-44
4. Gopal U, Bohonowych JE, Lema-Tome C, Liu A., Garrett-Mayer E, Wang B, Isaacs, JS. A novel extracellular Hsp90 mediated co-receptor function for LRP1 regulates EphA2 dependent glioblastoma cell invasion. PLOS One. 2011 6(3):e17649.