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” tumor cultures to study the behavior of both tumors and the other 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 development or currently under clinical trial.

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. Herlyn 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 much of today’s new targeted therapeutics. In 1981, Herlyn became an assistant professor and established a laboratory that is, today, one the largest and most celebrated 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 cells, tumor formation, and drug resistance. These models also make a unique testing ground for ideas on future therapeutics or 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 long-term 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.

Another major effort of the Herlyn laboratory is the study of therapeutic 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.

1 - Magnitsky S, Roesch A, Herlyn M, Glickson JD., In vivo and ex vivo MR imaging of slowly cycling melanoma cells., Magnetic Resonance Medicine. 2011 Apr 26. doi: 10.1002/mrm.22917 [Epub ahead of print.], 21523820

2 - Somasundaram R, Villanueva J, Herlyn M., Will engineered T cells expressing CD20 scFv eradicate Melanoma?, Molecular Therapy. 2011 Apr;19(4):638-40. No abstract available., 21455210

3 - Vultur A, Villanueva J, Herlyn M., Targeting BRAF in advanced melanoma: a first step toward manageable disease., Clinical Cancer Research. 2011 Apr 1;17(7):1658-63. [Epub 2011 Mar 29.], 21447722

4 - Zabierowski SE, Fukunaga-Kalabis M, Li L, Herlyn M., Dermis-derived stem cells: a source of epidermal melanocytes and melanoma?, Pigment Cell & Melanoma Research. 2011 Jun;24(3):422-9. doi: 20.1111/j.1755-148X.2011.00847.x [Epub 2011 Mar 29.], 21410654

5 - Thurber AE, douglas G, Sturm EC, Zabierowski SE, Smit DJ, Ramakrishnan SN, Hacker E, leonard JH, Herlyn M. Sturm RA., Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumor xenografts regulate the NOTCH pathway., Oncogene. 2011 Feb 28. [Epub ahead of print], 21358674

6 - Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, et al., 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/p13K., Cancer Cell. 2010 Dec 14;18(6):683-95., 21156289

7 - Han MJ, Wang H, Beer LA, Tang HY, Herlyn M, Speicher DW., A systems biology analysis of metastatic melanoma using in-depth three-dimensional protein profiling., Proteomics. 2010 Dec;10(24):4450-62. doi: 10.1002/pmic.200900549. [Epub 2010 Nov 17], 21136598

8 - Herlyn M, Nathanson KL., Taking the guesswork out of uveal melanoma.[Editorial, Comment], New England Journal of Medicine. 2010 Dec 2;363(23):2256-7. [Epub 2010 Nov 17.], 21083377

9 - Herlyn M., Boris Bastian., Pigment Cell & Melanoma Research. 2010 Dec;23(6):834., 20973934

10 - Lee JT, Li L, Brafford PA, van den Eijnden M, Halloran MB, Sproesser K, Haass NK, Smalley KS, Tsai J, Bollag G, Herlyn M., PLX4032, a potent inhibotor of the B-RAF V600E oncogene, selectively inhibits V600E-positive melanomas., Pigment Cell & Melanoma Research. 2010 Dec;23(6):820-7., 20973932