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Jessie Villanueva, Ph.D.

Jessie Villanueva, Ph.D.

Laboratory

The Villanueva Laboratory

Contact

215-898-3971
jvillanueva@wistar.org

Assistant Professor, Molecular & Cellular Oncogenesis Program

Member, The Wistar Institute Melanoma Research Center

About the Scientist

Villanueva studies the molecular signaling pathways that become deregulated in melanoma with the goal of identifying suitable targets for therapy, particularly for tumors with limited therapeutic options.

Villanueva received her Bachelor of Science degree in biology at Universidad Peruana Cayetano Heredia in her native Peru. Following graduation, she joined the department of Pathology at the University of Pittsburgh School of Medicine as research specialist. She then enrolled in the graduate program at University of Miami School of Medicine and she earned a Ph.D. in Molecular Cell and Developmental Biology. She then pursued postdoctoral training at the University of Pennsylvania School of Medicine where she began her research in melanoma.  Villanueva joined The Wistar Institute as a postdoctoral fellow in the Herlyn laboratory, and was later appointed assistant professor in the molecular and cellular oncogenesis program.

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The Villanueva Laboratory

The Villanueva laboratory is actively studying the molecular mechanisms mediating drug resistance in melanoma, aiming at designing effective therapies that will overcome it. The lab has extensively investigated the role of the RAF/MEK and PI3K/mTOR pathways as therapeutic targets and the mechanisms underlying resistance to inhibitors that block these signaling cascades. More recently, the team is focusing on identifying new targets or vulnerabilities that can be therapeutically exploited in NRAS mutant melanoma, a tumor type in dire need of new treatments.

Staff

Postdoctoral Fellows

Hsin-Yi Chen, Ph.D.
Adam Guterres, Ph.D.

Research Assistant

Patricia Reyes-Uribe

Research

Mechanisms of Drug Resistance in Melanoma

The Villanueva lab has developed pre-clinical models that show how melanoma gains resistance to BRAF and MEK inhibitors. Using these models, we have demonstrated that melanoma cells treated with RAF inhibitors bypass the effects of the drugs by activating alternative signaling pathways, including RTKs, PI3K/mTOR and STAT3. As melanoma is a highly heterogeneous disease, multiple mechanisms of resistance are likely to arise in patients. The lab is using an array of biochemical and genetic approaches to identify additional mechanisms of drug resistance and testing combinations of clinically relevant inhibitors targeting the resistant pathways. The goal is to identify the best combination therapies that can overcome drug resistance or that could be used as salvage therapies for tumors refractory to current therapies.

Developing Molecular Approaches to Target NRAS Mutant Melanomas

NRAS is a poorly characterized RAS family member, and the biology of NRAS mutant tumors remain inadequately understood. There are very limited treatment options for patients carrying NRAS mutations, which are present in more than 25 percent of all melanomas. As targeting NRAS directly has thus far not been possible, the aim of the lab is to eradicate this type of tumors by blocking critical RAS effectors or pathways that are essential for tumor survival.  We have identified a number of non-oncogene dependencies that are critical for survival of melanoma cells including BRD4, TERT and the ribosomal serine/threonine kinase S6K2. The lab is further investigating their role in melanoma and evaluating the impact of blocking their activity on tumor initiation, maintenance and survival using physiologically relevant models.

Selected Publications

Echevarría-Vargas, I.M., Reyes-Uribe, P.I., Villanueva, J., et al. "Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma." EMBO Mol Med. 2018 May;10(5). pii: e8446. doi: 10.15252/emmm.201708446.

Reyes-Uribe, P., Adrianzen-Ruesta, M.P., Villanueva, J., et al. "Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma." Oncogene. 2018 Apr 26. doi: 10.1038/s41388-018-0247-7. [Epub ahead of print]

Villanueva, J., Infante, J.R., Nathanson, K.L., et al. "Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma." Cell Rep. 2013 Sep 26;4(6):1090-9. doi: 10.1016/j.celrep.2013.08.023. Epub 2013 Sep 19.

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