The laboratory of Jessie Villanueva investigates the molecular signaling pathways that become deregulated in melanoma with the goal of identifying suitable targets for therapy. The Villanueva lab is actively studying the molecular mechanisms mediating drug resistance in melanoma aiming at designing effective therapies that will overcome it. The team is particularly interested in the role of the RAF/MEK/ERK pathway as therapeutic target and the mechanisms underlying resistance to inhibitors that block these signaling cascades.

Villanueva joined The Wistar Institute in 2006 as a postdoctoral fellow in the laboratory of Meenhard Herlyn, D.V.M., D.Sc., where she later became a staff scientist. Jessie studied biology at Universidad Peruana Cayetano Heredia in her native Peru, where she would receive her Bachelor of Science degree. Following graduation, she moved to Pennsylvania to become a research specialist at the University of Pittsburgh School of Medicine. She then enrolled in the graduate program at University of Miami School of Medicine where she began her dissertation studies on the role of adhesion and signaling pathways in regulating the cell cycle—work with great relevance to the part these pathways play in the development of cancer.

In 2003, she earned a Ph.D. in Molecular Cell and Developmental Biology. She then pursued postdoctoral training at the University of Pennsylvania School of Medicine. There, she began to further investigate the role of a mutation in the BRAF gene that has been discovered to be mutated in half of all cases of melanoma, an aggressive form of skin cancer whose rates have climbed steadily in recent years. The mutant BRAF turns on a signaling pathway that drives cell division and, tumor formation.

At Wistar, Villanueva’s work has demonstrated that recently developed RAF inhibitors are, at best, transient in their tumor-killing effectiveness. In a 2010 article published in the journal Cancer Cell, she presented findings that show how tumor cells are able to adapt to RAF inhibitors and find a way to bypass the effects of the drug.

As melanoma is a highly heterogeneous disease, multiple mechanisms of resistance are likely to arise in patients. The Villanueva laboratory is using an array of biochemical and genetic approaches to identify additional mechanisms of intrinsic and acquired resistance and test combinations of different inhibitors targeting pathways including MEK and PI3K. Their goal is to identify the best combination therapies that can overcome drug resistance and could move forward into clinical trials.

1 - Feng, Y., Barile, E., De, S. K., Stebbins, J. L., Cortez, A., Aza-Blanc, P., Villanueva, J., Heryln, M., Krajewski, S., Pellecchia, M., Ronai, Z. A. and Chiang, G. G. Effective inhibition of melanoma by BI-69A11 is mediated by dual targeting of the AKT and NF-κB pathways. Pigment Cell & Melanoma Research. 2011; doi: 10.1111/j.1755-148X.2011.00867.x

2 - Villanueva J, Vultur A, and Herlyn, M. Resistance to BRAF inhibitors: Unraveling mechanisms and future treatment options. Cancer Research. 2011; In press.

3 - Somasundaram R, Villanueva J, Herlyn, M. Will Engineered T cells Expressing CD20 scFv Eradicate Melanoma? Mol Ther. 2011;19(4):638-40. (PMID: 21455210)

4 - Vultur, A, Villanueva J, Herlyn, M. Targeting BRAF in advanced melanoma: a first step towards manageable disease. Clin Cancer Res. 2011;17(7):1658-63. Epub 2011 Mar 29. (PMID: 21447722)

5 - Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D'Andrea K, Pushparajan A, Hayden JE, Brown KD, Laquerre S, McArthur GA, Sosman JA, Nathanson KL, Herlyn M. Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010; 18(6):683-95. (PMID:21156289)

6 - Vultur A, Villanueva J, Herlyn M. BRAF inhibitor unveils its potential against advanced melanoma. Cancer Cell. 2010; 18(4):301-2. (PMID: 20951940)

7 - Smalley KS, Xiao M, Villanueva, J, Nguyen TK, Flaherty KT, Letrero R, Van Belle P, Elder DE, Wang Y, Nathanson KL, Herlyn M. CRAF inhibition induces Bcl-2 dependent apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene. 2009; 28(1):85-94. (PMID: 18794803)

8 - Villanueva, J., Herlyn, M. Melanoma (version 2.0). In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons. 2009; p.1-9 [Epub March 15]

9 - Villanueva, J., Herlyn, M.: Melanoma and the tumor microenvironment. Curr. Oncol. Rep. 2008; 10(5):439-446 (PMID: 18706274)

10 - Villanueva, J., Yung, Y, Walker, J and Assoian RK. ERK activity and G1 phase progression: identifying dispensable and essential activities and primary versus secondary targets. Mol. Biol. Cell. 2007; 18(4):1457-1463 [Epub ahead of print February 21].