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Meenhard Herlyn, D.V.M., D.Sc.

Meenhard Herlyn, D.V.M., D.Sc.

  • Caspar Wistar Professor in Melanoma Research
  • Director, The Wistar Institute Melanoma Research Center
  • Professor, Molecular and Cellular Oncogenesis Program
  • 215-898-3950, Office
  • 215-898-0980, Fax
Meenhard Herlyn’s laboratory at The Wistar Institute focuses on the biology that underlies melanoma, the most aggressive form of skin cancer. His efforts have pioneered the use of the three-dimensional “artificial skin” cultures to study the behavior of both tumor and normal cells that sustain tumor growth, a system known as the tumor microenvironment. The Herlyn laboratory has transformed the scientific understanding of stem cells as they relate to cancer, and their work on the networks of signaling pathways in melanoma has formed the basis of numerous therapies now in clinical trials or very recently approved.
Born and educated in Germany, Herlyn received his D.V.M. at the University of Veterinary Medicine, Hanover in 1970 and went on to receive a D.Sc. in medical microbiology at the University of Munich in 1976. He came to The Wistar Institute as an associate scientist in 1976, where he worked in the emerging field of monoclonal antibodies, a technology that formed the basis of a portion of today’s new targeted therapeutics. In 1981, Herlyn became an assistant professor and established a laboratory that is, today, one the largest and best known research groups on the study of melanoma biology.
The ability to model the microenvironment of normal and diseased human tissue through 3-D artificial skin provides the Herlyn laboratory with a unique insight into cancer research. Growing cells in these tissue-like models induces major changes in gene expression similar to those in animals and patients, making them superbly suited for studies of signaling between normal and malignant cells, tumor formation, and drug resistance. These models also make a unique testing ground for ideas on future therapeutics and drug combinations.
The Herlyn laboratory also seeks to further define the various signaling pathways that work in cancer cells in order to discover new opportunities to inhibit cancer growth through targeted therapeutics. Since therapy is increasingly guided by the genetic aberrations in tumors, Herlyn and his colleagues are developing combinations of compounds that take into account the genetic signature of tumors, with the specific goal of individualized cancer therapy.
Currently, the Herlyn laboratory collaborates with pharmaceutical companies as well as academic chemists and structural biologists to select and further develop compounds for tumor inhibition. Tumor heterogeneity, i.e. the differences between cells within one tumor, among different tumor lesions of the same patient, or between patients even if the tumors are of similar genetic signatures, provide major challenges for future therapy. The laboratory is developing biological signatures of melanoma cells that take into account the various forms of heterogeneity.
Another major effort of the Herlyn laboratory is the study of therapy resistance and tumor dormancy. Tumor cells can become dormant in primary tumors or at any time after metastatic dissemination and can persist in the dormant state for many years, allowing tumors to resist treatment. Herlyn’s working hypothesis is that defined tumor subpopulations are central to dormancy and drug resistance due to their slow turnover and their non-responsiveness to growth signals. His efforts seek to define how tumor cells escape dormancy for growth, invasion, and metastasis, and how to best develop strategies for therapy.
Selected Publications (2013 Only)

1.    Balaburski, G.M., Leu, J.I., Beeharry, N., Hayik, S., Andrake, M.D., Zhang, G., Herlyn, M., Villanueva, J., Dunbrack, R.L., Yen, T., George, D.L., Murphy, M.E.: A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol. Cancer Res. 11:219-229, 2013. PMID: 23303345 (PMC: 3606282)

2.    Krepler, C., Chunduru, S.K., Halloran, M.B., He, X., Xiao, M., Vultur, A., Villanueva, J., Mitsuuchi, Y., Neiman, E.M., Benetatos, C., Nathanson, K.L., Amaravadi, R.K., Pehamberger, H., McKinlay, M., and Herlyn, M.: The novel SMAC inhibitor birinapant exhibits potent activity against human melanoma cells. Clin. Cancer Res. 19: 1784-1794, 2013. PMID: 23403634 (PMC: 3618595)

3.    Desai, B.M., Villanueva, J., Nguyen, T-T.K., Lioni, M., Xiao, M., Kong, J., Krepler, C., Vultur, A., Flaherty, K.T., Nathanson, K.L., Smalley, K.S.M., Herlyn, M.: The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One, 8(3):e59588 doi:10:1371/journal.pone.0059588, 2013. PMID: 23527225

4.    Vultur, A., Villanueva, J., Krepler, C., Rajan, G., Chen, Q., Li, L., Gimotty, P., Wilson, M., Hayden, J., Keeney, F., Nathanson, K.L., Herlyn, M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene April 29 [Epub ahead of print], 2013. PMID: 23624919

5.     Aird, K.M., Zhang, G., Li, H., Tu, Z., Bitler, B.G., Garipov, A., Wu, H., Wei, Z., Wagner, S.N., Herlyn, M., Zhang, R. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Rep. 3:1-4, 2013. PMID: 23562156 (PMC in Process, NIHMS466586)

6.     Roesch, A., Vultur, A., Bogeski, I., Wang, H., Zimmermann, K.M., Speicher, D., Körbel, C., Laschke, M.W., Gimotty, P.A., Philipp, S.E., Krause, E., Pätold, S., Villanueva, J., Krepler, C., Fukunaga-Kalabis, M., Hoth, M., Bastian, B., Vogt, T., Herlyn, M.: Overcoming intrinsic multi-drug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1Bhigh cells. Cancer Cell 23: 811-825. 2013. PMID: 23764003

7.     Reuveni, H., Flashner-Abramson, E., Steiner, L., Makedonski, K., Song, R., Shir, A., Herlyn, M., Bar-Eli, M., Levitzki, A.: Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 73: 4383-4394, 2013. PMID: 23651636

8.     Villanueva, J., Infante, J., Krepler, C., Reyes-Uribe, P., Samanta, M., Chen, H-Y, Li, B., Swoboda, R., Wilson, M., Vultur, A., Fukunaga-Kalabis, M., Wubbenhorst, B., Liu, Q., Sproesser, K., DeMarini, D., Gilmer, T., Martin, A-M., Marmorstein, R., Schultz, D., Speicher, D., Karakousis, G., Xu, W., Amaravadi, R., Xu, X.,  Schuchter, L., Herlyn, M., Nathanson, K.: Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Reports, in press, 2013.

9.      Nallet-Staub, F., Marsaud, V., Li, L., Gilbert, C., Dodier, S., Bataille, V., Sudol, M., Herlyn, M., Mauviel, A.: Pro-invasive activity of the Hippo pathway effectors YAP and TAZ in cutaneous melanoma. J Invest. Dermatol Jul 29 [epub ahead of print], 2013. PMID: 23897276

10.     Basu, D., Bewley, A.F., Sperry, S.M., Montone, K.T., Gimotty, P.A., Rasanen, K., Facompre, N.D., Weinstein, G.S., Nakagawa, H., Diehl, J.A., Rustgi, A.K., Herlyn, M: EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squameous cell carcinoma. Molec. Cancer Ther., in press, 2013