Department of Dermatology

https://www.ohsu.edu/dermatology

Group Leaders

Elizabeth Berry, MD and Sancy Leachman, MD, PhD

Group Members

Elizabeth Berry, MD and Sancy Leachman, MD, PhD

Publications

Wistar Institute
3601 Spruce Street, Room 472
Philadelphia, PA 19104
Information: Jessica L. Kohn, jkohn@wistar.org
215-495-6883

Group Leader

Dr Meenhard Herlyn
Caspar Wistar Professor in Melanoma Research
Director, The Wistar Institute Melanoma Research Centre
Professor, Molecular and Cellular Oncogenesis Program

Group Members

Dr. Mizuho Kalabis, Research Assistant Professor
Dr. Clemens Krepler, Research Assistant Professor
Dr. Shyam Somasundaram, Research Assistant Professor
Dr. Gao Zhang, Staff Scientist
Dr. Jianglan Liu, Associate Staff Scientist
Trish Brafford, Wistar Research Assistant
Dr. Ling Li, Wistar Research Assistant
Katrin Sproesser, Wistar Research Assistant
Marilda Beqiri, Research Assistant III
Josh Wang, Research Assistant II
Min Xiao, Research Assistant IV
Brian Gavin, Technician II
Jessica L. Kohn, Laboratory Coordinator

Research

Dr. 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.

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, Dr. 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, provides 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. Dr. 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.

 

Publications

Shannan B, Chen Q, Watters A, Perego M, Krepler C, Thombre R, Li L, Rajan G, Peterson S, Gimotty PA, Wilson M, Nathanson KL, Gangadhar TC, Schuchter LM, Weeraratna AT, Herlyn M, Vultur A. Enhancing the evaluation of PI3K inhibitors through 3D melanoma models. Pigment Cell Melanoma Res. 2016;29:317-28. PMID26850518 (PMCID4840066)

Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized preclinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2016;22:1592-602. PMID26673799 (PMCID4818716)

Brafford P, Sproessor K, Krepler C, Herlyn M. 1205Lu is human melanoma depending on the source. J Cancer Sci Ther. 2016;8:113.

Lu H, Liu S, Zhang G, Kwong LN, Zhu Y, Miller JP, Hu Y, Zhong W, Zeng J, Wu L, Krepler C, Sproesser K, Xiao M, Xu W, Karakousis GC, Schuchter LM, Field J, Zhang PJ, Herlyn M, Xu X, Guo W. Oncogenic BRAF-mediated melanoma cell invasion. Cell Rep. 2016;15:2012-24. PMID27210749 (PMCID4889462)

Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016;126:1834-56. PMID27043285 (PMCID4855947)

McNeal AS, Liu K, Nakhate V, Natale CA, Duperret EK, Capell BC, Dentchev T, Berger SL, Herlyn M, Seykora JT, Ridky TW. CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma. Cancer Discov. 2015;5(10):1072-85. PMID26183406 PMCID4592422

Wang YJ, Herlyn M. The emerging roles of Oct3 in tumor-initiating cells. Am J Physiol Cell Physiol. 2015;309(11):C709-18. PMID26447206

Krepler C, Xiao M, Spoesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos P, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized pre-clinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2015 Dec 16 [Epub ahead of print]. PMID26673799

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Bonyadi Rad E, Haass NK, Soyer HP, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response casues multidrug tolerance in melanoma. Oncogene. 2015;34(34):4448-59. PMID25417704; PMCIDPMC4442085.

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. 2015;137:1503-8. PMID25754407, PMC4496263

Cierlitza M, Chauvistre H, Bogeski I, Zhang X, Hauschild A, Herlyn M, Schadendorf D, Vogt T, Roesch A. Mitochondiral oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma subpopulations. Exp Dermatol. 2015;24:155-157. PMID25453510

Kraya AA, Piao S, Xu X, Zhang G, Herlyn M, Gimotty P, Levine B, Amaravadi RK, Speicher DW. Identification of secreted proteins that reflect autophagy dynamics within tumor cells. Autophagy. 2015;11:60-74. PMID25484078

Webster MR, Xu M, Kinzler KA, Kaur A, Appleton J, O’Connell MP, Marchbank K, Valiga A, Dang VM, Perego M, Zhang G, Slipicevic A, Keeney F, Lehrmann E, Wood W 3rd, Becker KG, Kossenov AV, Frederick DT, Flaherty KT, Xu X, Herlyn M, Murphy ME, Weeraratna AT. Wnt5a promotes and adaptive, senescence-like stress stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res. 2015;28:184-195. PMID25407936

Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drablos F, Lennartsson, A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi A, Arner A, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, Fairbairn L, Faulkner GJ, Ferrai C, Fisher ME, Forrester L, Goldowitz D, Guler R, Ha T, Hara M, Herlyn M, Ikawa T, Kai C, Kawamoto H, Khachigian L, Klinken PS, Kojima S, Koseki H, Klein S, Mejhert N, Miyaguchi K, Mizuno Y, Morimoto M, Morris KJ, Mummery C, Nakachi Y, Ogishima S, Okada-Hatakeyama M, Okazaki Y, Orlando Y, Ovchinnikov D, Passier R, Patrikakis M, Pombo A, Qin XY, Roy S, Sato H, Savvi S, Saxena A, Schwegmann A, Sugiyama D, Swoboda R, Tanaka R, Tomoiu A, Winteringham LN, Wolvetang E, Yanagi-Mizuochi C, Yoneda M, Zabierowski S, Zhang P, Abugessaisa I, Bertin N, Diehl AD, Fukuda S, Furuno M, Harshbarger J, Hasegawa A, Hori F, Ishikawa-Kato S, Ishizu Y, Itoh M, Kawashima T, Kojima M, Kondo N, Lizio M, Meehan TF, Mungall CJ, Murata M, Nishiyori-Sueki H, Sahin S, Sato-Nagao S, Severin J, de Hoon MJL, Kawai J, Kasukawa T, Lassmann T, Suzuki H, Kawaji H, Summers KM, Wells C, Hume DA, Forrest ARR, Sandelin A, Carninci P, Hayashizaki Y. Gene regulation; transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science. 2015;347:1010-4. PMID25678556

Slipicevic A, Herlyn M. KIT in melanoma: Many shades of grey. J Invest Dermatol. 2015;135:337-8. PMID25573046

Wang T, Xiao M, Ge Y, Krepler C, Belser E, Lopez-Coral A, Xu X, Zhang G, Azuma R, Liu Q, Liu R, Li L, Amaravadi RK, Xu W, Karakousis G, Gangadhar TC, Schuchter LM, Lieu M, Khare S, Halloran MB, Herlyn, M, Kaufman, R. BRAF inhibition stimulates melanoma-associated macrophages to drive tumor growth. Clin Cancer Res. 2015;21:1652-1664. PMID25617424

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. [Epub ahead of print, 6 Mar. 2015] PMID25754407

Fukunaga-Kalabis M, Hristova DM, Wang JX, Li L, Heppt MV, Wei Z, Gyurdiev A, Webster MR, Oka M, Weeraratna AT, Herlyn M. UV-induced Wnt7a in the human skin microenvironment specifies the fate of neural crest-like cells via suppression of Notch. J Invest Dermatol. 2015;135:1521-1532. PMID25705850

Liang C; FANTOM Consortium [….Herlyn M….], Forrest AR, Wagner GP. The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nat Comm. 2015;6:6066. PMID25585899

Yoshihara M, Ohmiya H, Hara S, Kawasaki S, FANTM consiortium […Herlyn M….], Hayashuzaki, Y, Itoh M, Kawaji H, Tsujikawa M, Nishida K. Discovery of molecular markers to discriminate corneal endothelial cells in the human body. PLoS One. 2015;10(3):e0117581. PMID25807145

Liu S, Tetzlaff MT, Wang T, Yang R, Xie L, Zhang G, Krepler C, Xiao M, Bequiri M, Xu W, Karakousis G, Schuchter L, Amaravadi RK, Xu W, Wei Z, Herlyn M, Yao, Y, Zhang L, Wang Y, Zhang K. Xu X. miR-200c/Bmi1 axis and epithelial-mesenchymal transition contribute to acquire resistance to BRAF inhibitor treatment. Pigment Cell Melanoma Res. 2015;28:431-41. PMID25903073

Kim H, Frederick DT, Levesque MP, Cooper ZA, Fang Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn M, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai ZA. Downregulation of the ubiquitin ligase RNF125 underlies resistance of melanoma cells to BRAF inhibitors via JAK1 deregulation. Cell Rep. 2015;11:1458-73. PMID26027934

Vultur A, Smalley K, Herlyn M. Melanoma. In: Gelman EP, Sawyer CL, Rauscher III FJ, eds. Molecular Oncology: Causes of Cancer and Targets for Treatment. West Nyack, NY: Cambridge University Press; 2014:698-703.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2014;134:1108-1118. PMID24157461

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. 2014;134:123-132. PMID23897276

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2014;33:1850-1861. PMID23624919 (PMC3769503)

Geserick P, Herlyn M, Leverkus M. On the TRAIL to overcome BRAF-inhibitor resistance. J Invest Dermatol. 2014;134:315-8. PMID24424456

Ma X-H, Pioa S-F, Dey S, Mcafee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, Lazova R, Klump V, Pawelek JM, Xu X, Schuchter LM, Davies MA, Herlyn M, Winkler J, Koumenis C, Amaravadi RK. Targeting ER stress induced autophagy overcomes resistance to BRAF inhibition in melanoma. J Clin Invest. 2014;124:1406-1417. PMID24569374

Peng H, Talebzadeh-Farrooji M, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Carolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KL, Rauscher FJ 3rd. LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase. Cancer Res. 2014;74:1390-1403. PMID24590809

Arner E, Forrest AR, Ehrlund A, Mejhert N, Itoh M, Kawaji H, Lassmann T, Laurencikiene J, Rydén M, Arner P, FANTOM Consortium (…Herlyn M…). Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells. PLoS One. 2014;9(3):e80274. PMID24676332

Hasegawa Y, Tang D, Takahashi N, Hayashizah Y, Forrest AR, FANTOM Consortium (…Herlyn M…), Suzuki H. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes. Sci Rep. 2014;4:5228. PMID24957798

Yang R, Zhend Y, Li L, Liu S, Spata M, Wei Z, Nace A, Herlyn M, Cui R, Guo W, Cotsarelis G, Xu X. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat Comm. 2014;5:5807. PMID25510211

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Rad BE, Hass N, Soyer P, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response causes multi-drug tolerance in melanoma. Oncogene. 2014;1-12. PMID25619837

Slipicevic A, Somasundaram S, Sproesser K, Herlyn M. Isolation of melanoma subpopulations using negative selection. Methods Mol Biol. 2014;1102:501-512. PMID24258995

Liu J, Fukunaga-Kalabis M, Li L, Herlyn M. Developmental pathways activated in melanocytes and melanoma. Arch Biochem Biophys. 2014;563C:13-21. PMID25109840

Zhang G, Herlyn M. Linking SOX10 to slow-growth resistance phenotype. Cell Res. 2014;24:906-907. PMID24853952

Somasundaram R, Herlyn M. Indomethacin to the rescue of TRAIL-resistant melanomas. J Invest Dermatol. 2014;134:1198-1199. PMID24732334

Andersson R, Gebhard C,Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F; FANTOM Consortium (…Herlyn M…), Forrest AR, Carninci P, Rehli M, Sandelin A. An atlas of active enhancers across human cell types and tissues. Nature. 2014;27;507(7493):455-61. PMID24670763

Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nagao-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, Standley, DM, Date H, Sakaguchi S; FANTOM Consortium (…Herlyn M…). Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proc Natl Acad Sci USA. 2014;111:5289-5294. PMID24706905

Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, Haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Y, Kaiho A, Saka A, Hasegawa A, Knox A, Mackay-Sim A, Edge A, Bonetti A, Diehl A, Favorov A, Meynert A, Saxena A, Joshi A, Califano A, Lennartsson A, Gibson A, Kwon A, Schwegmann A, Beckhouse A, Mathelier A, Blumenthal A, Sajantila A, Pain A, Kasianov A, Kubosaki A, Manabe R, Bodega B, Marchand B, Jankovich B, Cannistraci CV, Davis C, Furlanello C, Plessy C, Kai C, Schmidl C, Wells C, Mummery C, Schneider C, Sugiyama D, Goldowitz D, de Lima Morais D, Albanese D, Vijayan D, Ovchinnikov D, Valen E, Dalla E, Wood E, Saijyo E, Schultes E, van Nimwegen E, Wolvetangg E, Drabløs D, Brombacher F, Hori F, Nakahara F, Altschuler G, Faulkner G, Jurman G, Schulze-Tanzil G, Sheng G, Fang H, Clevers H, Koseki H, Persson H, Enomoto H, Tatsukawa H, Sato H, Ohmiya H, Morikawa H, Nishiyori H, Satoh H, Toyoda H, Kawamoto H, Ohno H, Tanaka H, Carbajo D, Shimoji H, Motohashi H, Jia H, Hoof I, Vorontsov I, Alam I, Briggs J, Prendergast J, Shin J, Harshbarger J, Laros J, Mar J, Archer J, Ramilowski J, Blake J, Kempfle J, Kere J, Gough J, Takai J, Furusawa J, Li K, Kaida K, Ekwall K, Kajiyama K, Moro K, Iida K, Hitchens K, Nakazato K, Summers K, Lipovich L, Khachigian L, Winteringham L, Huminiecki L, Babina M, Fisher M, Rashid M, van de Wetering M, Chierici M, Roncador M, Patrikakis M, Okada-Hatakeyama M, Thompson M, Frith M, Farach-Carson M, Furuno M, Hamaguchi M, Suzuki M, Yamamoto M, Harbers M, Edinger M, Burroughs AM, Herlyn M, Detmar M, Fagiolini M, Tagami M, Kojima M, Yoneda M, Endoh M, Ohshima M, Hara M, Morimoto M, Murata M, Sakai M, Rye M, Kanamori-Katayama M, Ohkura N, Takahashi N, Kondo N, Mejhert N, Ninomiya N, Hofmann O, Rackham O, Rizzu P, ‘t Hoen P, Arner P, Zhang P, Klinken P, Balwierz P, Guler R, Fujita R, Passier R, Verardo R, Swoboda R, Kato S, Baker S, Krampitz S, Nagao-Sato S, Ho Sui S, Yoshida S, Koyasu S, Sakaguchi S, Katayama S, Fukuda S, Noma S, Watanabe S, Kawaguchi S, Piazza S, Zucchelli S, Kojima S, Ogishima S, Gustincich S, Roy S, Zabierowski S, Savvi S, Guhl S, Pradhan Bhatt S, Nozaki T, Dohi T, Sugiyama T, Hashimoto T, Toyoda T, Geijtenbeek T, Sengstag T, Gingeras T, Ha T, Ravasi T, Ikawa T, Kenna T, Kitamura T, Nakamura T, Kawashima T, Orlando V, Lee W, Wasserman W, Zhao W, Ciani Y, Okazaki Y, Shimoni Y, Yonekura Y, Yamaguchi Y, Mizuno Y, Hasegawa Y, Kawamura Y, Nakamura Y, Chen Y, Nakachi Y, Tatum Z, Suzuki H, Daub C, Kawai J, Heutink P, Hide W, Lenhard B, Bajic V, Makeev V, Sandelin A, Hume D, Carninci P, van den Berg L, Fairbairn L, Kaczkowski B, Lilje B, Simon C, Motakis E, Kasukawa T, Arakawa T, Suzuki N, Young R. A promoter level mammalian expression atlas. Nature. 2014;507:462-470. PMID24670764

Somasundaram R, Herlyn M. Relapse of melanoma after successful adoptive T-cell therapy: escape through inflammation-induced phenotypic melanoma plasticity. Pigment Cell Melanoma Res. 2013;26:2-4.

Balaburski GM, Leu JI, Beeharry N, Hayik S, Andrake MD, Zhang G, Herlyn M, Villanueva J, Dunbrack RL, Yen T, George DL, Murphy ME. A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res. 2013;11:219-229.

Krepler C, Chunduru SK, Halloran MB, He X, Xiao M, Vultur A, Villanueva J, Mitsuuchi Y, Neiman EM, Benetatos C, Nathanson KL, Amaravadi RK, Pehamberger H, McKinlay M, Herlyn M. The novel SMAC inhibitor birinapant exhibits potent activity against human melanoma cells. Clin Cancer Res. 2103;19:1784-1794.

Wang T, Somasundaram R, Herlyn M. Combination therapy of immunocytokines with Ipilimumab: a cure for melanoma? J Invest Dermatol. 2013;133(3):595-596.

Li L, Fukunaga-Kalabis M, Herlyn M. Isolation, characterization, and differentiation of human multipotent dermal stem cells. Methods Mol Biol. 2013;989:235-246.

Swoboda R, Herlyn M. There is a world beyond protein mutations: the role of non-coding RNAs in melanomagenesis. Exp Dermatol. 2013;22:303-306.

Wang T, Herlyn M. The macrophage: a new factor in UVR-induced melanomagenesis. J Invest Dermatol. 2013;133:1711-1713.

Vultur A, Herlyn M. Snapshot: melanoma. Cancer Cell. 2013;23:706.

Merlino G, Flaherty K, Acquavella N, Day CP, Aplin A, Homen S, Topalian S, Van Dyke T, Herlyn M. The future of preclinical mouse models in melanoma treatment is now. Pigment Cell Melanoma Res. 2013;26:E8-E14.

Kastl A, Dieckman S, Wähler K, Völker T, Kastl L, Shannan B, Harms K, Ocker M, Parak W, Herlyn M, Meggers E. Rhenium complexes with visible-light-induced anticancer activity. Organometallic Med Chem. 2013;8:924-927.

Desai BM, Villanueva J, Nguyen T-TK, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KSM, Herlyn M. The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One. 2013;8(3):e59588.

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2013;33:1850-61. PMID23624919 (PMCID3769503)

Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M, Zhang R. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Rep. 2013;3:1-4.

Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, Körbel C, Laschke MW, Gimotty PA, Philipp SE, 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 JARID1B(high) cells. Cancer Cell. 2013;23:811-825.

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. 2013;73:4383-4394.

Kwak J, Gallagher M, Ozdener MH, Wysocki CJ, Goldsmith BR, Isamah A, Faranda A, Fakharzadeh SS, Herlyn M, Johnson ATC, Preti G. Volatile biomarkers from human melanoma cells. J Chromatography B Analyt Technol Biomed Life Sci. 2013;931:90-96.

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, Chen TY, 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. 2013;4:1090-1099.

Basu D, Bewley AF, Sperry SM, Montone KT, Gimotty PA, Rasanen K, Facompre ND, Weinstein GS, Nakagawa H, Diehl JA, Rustgi AK, Herlyn M. EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squamous cell carcinomas. Molec Cancer Ther. 2013;12:2176-2186.

Lee EK, Lian Z, D’Andrea K, Letrero R, Sheng W, Liu S, Diehl N, Barbash O, Schuchter LM, Amaravadi RK, Xu X, Herlyn M, Nathanson KL, Diehl JA. The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma. Mol Cell Biol. 2013;33:4422-4433.

Rasänen K, Speicher K, Valiga A, Tang H-Y, Zhang G, Perego M, Somasundaram R, Li L, Sriwasdi S, Klein-Szanto A, Basu D, Rustgi AK, Speicher DW, Herlyn M. Comparative secretome analysis of epithelial and mesenchymal subpopulations of head and neck squamous cell carcinoma identifies S100A4 as a potential therapeutic target. Molec Cell Proteomics. 2013;12(12):3778-92.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2013 Oct 24 [Epub ahead of print].

Wong GS, Lee JS, Park YY, Klein-Szanto AJ, Waldron TJ, Cukierman E, Herlyn M,
Gimotty P, Nakagawa H, Rustgi AK. Periostin cooperates with mutant p53 to mediate invasion through the induction of STAT1 signaling in the esophagus tumor microenvironment. Oncogenesis. 2013;2:e59.

O’Connell M, Marchbank K, Webster M, Valiga A, Kaur A, Vultur A, Li L, Herlyn M, Villanueva J, Liu Q, Yin X, Widura S, Nelson J, Ruiz N, Camilli T, Indig FE, Flaherty K, Wargo J, Frederick DT, Cooper Z, Nair S, Amaravadi R, Schuchter L, Karakousis G, Xu W, Xu X, Weeraratna AT. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Disc. 2013;3(12):1378-93.

Division of Genetic Epidemiology

University of Utah School of Medicine
391 Chipeta Way, Suite D
Salt Lake City, UT 84103

https://medicine.utah.edu/internal-medicine/epidemiology/genetic-epidemiology

Group Leader

Professor Lisa Cannon Albright, PhD
E-mail: lisa@genepi.med.utah.edu
Phone: 01 801 587-9300
Fax: 01 801 581-6052

https://medicine.utah.edu/faculty/lisa-cannon-albright

 

To find out more about the University of Pennsylvania please visit:
http://www.med.upenn.edu/

Our institution

National Cancer Institute

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Our group

American Melanoma Families Group
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd.
Bethesda, MD 20892-7236
USA

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The Group leader

Alisa M. Goldstein, Ph.D.
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd.
Bethesda, MD 20892-7236
USA

Tele: 01-301-496-4375
Fax: 01-301-402-4489
Email: goldstea@mail.nih.gov

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Our studies of familial melanoma began in the mid 1970’s as a clinical and epidemiologic evaluation of American families with two or more living members with melanoma. The study has evolved over the years to a more formal genetic epidemiologic investigation of families with three or more living members with melanoma. We have examined and followed over 2000 family members, some for over 25 years. We are actively accruing additional families in the U.S. and can be contacted at the above address.

Participants are evaluated either at the NIH Clinical Center or locally by the study team. The research team currently includes genetic epidemiologists, clinicians (physicians and nurses), and laboratory investigators. The major goals of the study are to investigate the genetic and environmental determinants of melanoma in families without known germline mutations; for families with CDKN2A mutations, to study the contribution of other genetic and environmental factors in the expression of disease, to estimate penetrance, and to examine gene-gene and gene-environment interactions.

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The names and e-mail addresses of the group members

Principal researchers

Margaret Tucker, MD
tuckerp@mail.nih.gov

Michael Sargen, MD
michael.sargen@nih.gov

Alisa Goldstein, PhD
goldstea@mail.nih.gov

Maria Teresa Landi, MD, PhD
landim@mail.nih.gov

Elizabeth Gillanders, PhD
Elizabeth.Gillanders@nih.gov

Rose Yang
royang@mail.nih.gov

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Publications

Newton Bishop JA, Harland M, Bennett DC, Bataille V, Goldstein AM, Tucker MA, Ponder BAJ, Cuzick J, Selby P, Bishop DT.
Mutation testing in melanoma families: INK4A, CDK4, and INK4D.
Br J Cancer 1999;80:295-300.

Shennan MG, Badin AC, Walsh S, Summers A, From L, McKenzie M, Goldstein AM, Tucker MA, Hogg D, Lassam N.
Lack of germline CDK6 mutations in familial melanoma.
Oncogene 2000;19:1849-1852.

Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA.
Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations.
J Natl Cancer Inst 2000;92:1006-1010.

Harland M, Holland EA, Ghiorzo P, Mantelli M, Bianchi-Scarra G, Goldstein AM, Tucker MA, Ponder BAJ, Mann GJ, Bishop DT, Newton Bishop J.
Mutation screening of the CDKN2A promoter in melanoma families.
Genes Chromosomes Cancer 2000;28:45-57.

Ciotti P, Struewing JP, Mantelli M, Chompret A, Avril MF, Santi PL, Tucker MA, Bianchi-Scarra G*, Bressac-de Paillerets B*, Goldstein AM*.
A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families.
Am J Hum Genet 2000;67:311-319.

Goldstein AM, Martinez M, Tucker MA, Demenais F.
Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in American melanoma-prone families.
Cancer Epidemiol Biomarkers Prev 2000;9:889-894.

Auroy S, Avril MF, Chompret A, Pham D, Goldstein AM, Bianchi-Scarra G, Frebourg T, Joly P, Spatz SA, Rubino C, Demenais F, French
Hereditary Melanoma Study Group, Bressac-de Paillerets B. Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a founder effect.
Genes Chromosomes Cancer 2001;32:195-202.

Goldstein AM, Liu L, Shennan MG, Hogg D, Tucker MA, Struewing JP.
A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families.
Br J Cancer 2001;85:527-530.

Goldstein AM, Tucker MA.
Genetic epidemiology of cutaneous melanoma – A global perspective.
Arch Dermatol 2001;137:1493-1496.

Mantelli M, Barile M, Ciotti P, Ghiorzo P, Lantieri F, Pastorino L, Catricalà C, Torre GD, Folco U, Grammatico P, Padovani L, Pasini B, Rovini D, Queirolo P, Rainero ML, Santi PL, Sertoli RM, Goldstein AM, Società Italiana Dermatologia e Venerologia Gruppo Italiano Studi Epidemiologici in Dermatologia, Bianchi-Scarrà G.
High prevalence of the G101W germline mutation in the CDKN2A (P16ink4a) gene in 62 Italian malignant melanoma families.
Am J Med Genet 2002;107:214-221.

Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH, Jr.
A natural history of melanomas and dysplastic nevi: An atlas of lesions in melanoma-prone families.
Cancer 2002;94:3192-3209.

Bishop DT*, Demenais F*, Goldstein AM*, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA, The Melanoma Genetics Consortium.
Geographical variation in the penetrance of CDKN2A mutations for melanoma.
J Natl Cancer Inst 2002;94:894-903.

Feng Y, Shi J, Goldstein AM, Tucker MA, Nelson MA.
Analysis of mutations and identification of several polymorphisms in the putative promoter region of the p34CDC2-related CDC2L1 gene located at 1p36 in melanoma cell lines and melanoma families.
Int J Cancer 2002;99:834-838.

Kefford R, Newton Bishop J, Tucker M, Bressac-de Paillerets B, Bianchi-Scarra G, Bergman W, Goldstein A, Puig S, Mackie R, Elder D, Hansson J, Hayward N, Hogg D, Olsson H, on behalf of the Melanoma Genetics Consortium.
Genetic testing for melanoma.
Lancet Oncol 2002; 3:653-4.

Tucker MA, Goldstein AM.
Melanoma etiology: where are we?
Oncogene 2003;22:3042-3052.

Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH, Jr.
A natural history of melanomas and dysplastic nevi: An atlas of lesions in melanoma-prone families.
Dermatol Nursing 2003;15:237-253.