STATEMENT OF RESEARCH

I am a cancer biologist and Japaneseboard-certified dermatologist. Myoverall career objective is to investigate and develop novel approaches for the treatment of melanoma, the most deadly form of skin cancer. Although significant advances have been made in the field of melanoma research in recent years, the diseasestill accounts for 10,000 deaths annually in the USA due to its ability to metastasize and develop resistance to current therapies.Therefore, there is an urgent need to develop approaches that not onlyprevent the progression of melanoma, but also overcome resistance to new drugs. Throughout my graduate and postdoctoral training, I have been particularly interested in studying signaling pathways that are shared by activated skin progenitor cells and malignant melanoma cells and that can drive plasticity associated with cancer. My research in the coming years will focus on three important themes: 1) investigating a link between the embryonic phenotype of cancer cells and the immune response they elicit; 2) identifying druggable targets involved in neural crest-like reprogramming; and 3) identifying genes critical for tumor development as potential targets for not only therapy but also prevention using a patient-derived iPS-melanoma model.

BIBLIOGRAPHY

Research Publications, Peer-Reviewed (in chronological order):

  1. Konishi H, Matsuzaki H, Takaishi H, Yamamoto T, Fukunaga M, Ono Y, Kikkawa U. Biochem Biophys Res Commun. 1999;264:840-846. PMID10544018
  2. Oka M, Nagai H, Ando H, Fukunaga M, Matsumura M, Araki K, Ogawa W, Miki T, Sakaue M, Tsukamoto K, Konishi H, Kikkawa U, Ichihashi M. Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells. J Invest Dermatol. 2000;115:699-703.PMID10998146
  3. Fukunaga M, Oka M, Ichihashi M, Yamamoto T, Matsuzaki H, Kikkawa U. Involvement of PKCactivated by tyrosine phosphorylation in ultraviolet-induced apoptosis in human keratinocyte HaCaT cell line. Biochem Biophys Res Commun. 2001;289:573-579.PMID11716513
  4. Fukunaga M, Masaki T, Ichihashi M, Ueda M.CD8-positive primary cutaneous anaplastic large cell lymphoma with a fair prognosis. Acta Derm Venereol.2002;82:312-314. PMID12361145
  5. Li G, Fukunaga M, Herlyn M. Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding beta-catenin signaling. Exp Cell Res.2004;297:142-151. PMID15194432
  6. Oka M, Kageyama A, Fukunaga M, Bito T, Nagai H, Nishigori C. Phosphatidylinositol 3-kinase/Akt-dependent and -independent protection against apoptosis in normal human melanocytesJ Invest Dermatol.2004;123:930-936. PMID15482482
  7. Fang D, Leishear K, Nguyen TK, Finko R, Cai K, Fukunaga M, Li L, Brafford PA, Kulp AN, Xu X, Smalley KS, Herlyn M. Defining the conditions for the generation of melanocytes from human embryonic stem cells. Stem Cells.2006;24:1668-1677. PMID16574754
  8. Fukunaga-Kalabis M, Martinez G, Liu Z-J, Kalabis J, Mrass P, Weninger W, Firth SM, Planque N, Perbal B, Herlyn M. CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. J Cell Biol.2006;175:563-569.PMID17101694;PMCID2064593
  9. Kalabis J, Li G, Fukunaga-Kalabis M, Rustgi A, Herlyn M. Endothelin-3 stimulates survival of goblet cells in organotypic cultures of human colonic epithelium. Am J Physiol - GI Liver Physiol. 2008;295:G1182-1189.PMID18832450; PMCID2604801
  10. Fukunaga-Kalabis M, Martinez G, Telson SM, Liu Z-J, Balint K, Juhasz I, Elder DE, Perbal B, HerlynM. Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene. 2008;27:2552-2560. PMID17968313; PMCID1994712
  11. Li L*, Fukunaga-Kalabis M*, Yu H, Xu X, Kong J, Lee JT, Herlyn M. Human dermal stem cells differentiate into functional epidermal melanocytes. J Cell Sci.2010;123:853-860. PMID20159965; PMCID2831759 (*co-first author)
  12. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, Basu D, Gimotty P, Vogt T, Herlyn M. A temporarily distinct subpopulationof slow-cycling melanoma cells isrequired forcontinuous tumor growth. Cell.2010;141:583-594.PMID204782552; PMCID2882693
  13. Fukunaga-Kalabis M, Martinez G, Nguyen T-TK, Kim D, Santiago-Walker A, Roesch A, Herlyn M. Tenascin promotes melanoma progression by maintaining the ABCB5-positive side population. Oncogene.2010;29:6115-6124. PMID2072997; PMCID2991494
  14. Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D’Andrea K, Pushparajan A, Hayden JE, Dahlman K, Laquerre S, McArthur G, Sosman J, Nathanson KL, Herlyn M.Acquired resistance to BRAF inhibitors mediated by an A/B/C RAF kinase switch in melanoma can be overcome by co-targeting MEK and IGF-1R/PI3K. Cancer Cell.2010;18:683-695. PMID21156289; PMCID3026446
  15. Li L, Fukunaga-Kalabis M, Herlyn M. The three-dimensional human skin reconstruct model: a tool to study normal skin and melanoma progression. J Vis Exp. 2011;54:e2937 PMID21847077; PMCID3159964
  16. Zabierowski SE, Baubet V, Himes B, Li L, Fukunaga-Kalabis M, Patel S, McDaid R, Guerra M, Gimotty P, Dahamne N, Herlyn M. Direct reprogramming of melanocytes to neural crest stem-like cells by one defined factor. Stem Cells.2011;11:1752-62. PMID21948558
  17. Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, Körbel C, Laschke MW, Gimotty PA, Philipp SE, Krause E, Pätzold S, Villanueva J, Krepler C, Fukunaga-Kalabis M, Hoth M, Bastian BC, Vogt T, Herlyn M. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells.Cancer Cell. 2013;23:811-825. PMID23764003
  18. Yang Y, Wu J, Demir A, Castillo-Martin M, Melamed RD, Zhang G, Fukunaga-Kalabis M, Perez-Lorenzo R, Zheng B, Silvers DN, Brunner G, Wang S, Rabadan R, Cordon-Cardo C,Celebi JT. GAB2 induces tumor angiogenesis in NRAS-driven melanoma. Oncogene. 2013;32:3627-3637. PMID22926523
  19. Villanueva J, Infante JR, Krepler C, Reyes-Uribe P, Samanta M, Chen H, Li B, Swoboda R, Wilson M, VulturA,Fukunaga-Kalabis M, Wubbenhorst B, Liu Q, Sproesser K, DeMarini DJ, Gilmer TM, Martin A, Marmorstein R,Schultz D, Speicher D, Karakousis GC, Xu W,Amaravadi RK, Xu X, Schuchter LM, Herlyn M, Nathanson KL. Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Report. 2013;4:1090-1099. PMID24055054; PMCID3956616

Research Publications, Peer-Reviewed Reviews:

  1. Ichihashi M, Ueda M, Budiyanto A, Bito T, Oka M, Fukunaga M, Tsuru K, Horikawa T. UV-induced skin damage. Toxicology.2003;189:21-39. PMID12821280
  2. Fukunaga-Kalabis M, Santiago-Walker A, Herlyn M. Matricellular proteins produced by melanocytes and melanomas: in search for functions. Cancer Microenviron.2008;1:93-102. PMID19308688; PMCID2654351
  3. Zabierowski SE, Fukunaga-Kalabis M, Li L, Herlyn M. Dermis-derived stem cells: a source of epidermal melanocytes and melanoma? Pigment Cell Melanoma Res.2011;24:422-429. PMID21410654
  4. Fukunaga-Kalabis M, Roesch A, Herlyn M. From cancer stem cells to tumor maintenance cells. J Invest Dermatol. 2011;131:1600-16041. PMID21654838
  5. Li L, Fukunaga-Kalabis M, Herlyn M. Isolation and cultivation of dermal stem cells that differentiate into functional melanocytes. Methods Mol Biol.2012;806:15-29. PMID22057442
  6. Li L, Fukunaga-Kalabis M, Herlyn M. Isolation, characterization, and differentiation of human multipotent dermal stem cells.Methods Mol Biol. 2013;989:235-246. PMID23483399

Research Publications, Non-PeerReviewed:

  1. Fukunaga-Kalabis M, Li L, Herlyn M.Three-dimensional culture of human skin. AACR Education Book. 2007:203-206.
  2. Fukunaga-Kalabis M, Herlyn M. Unraveling mysteries of the multifunctional protein SPARC. J Invest Dermatol.2007;127:2497-2498. PMID17934501
  3. Herlyn M, Fukunaga-Kalabis M. What is a good model for melanoma? J Invest Dermatol. 2010;130:911-912. PMID20231823
  4. Fukunaga-Kalabis M, Herlyn M. Beyond ABC: another mechanisms of drug resistance in melanoma side population. J Investig Dermatol. 2012;132:2317-2319. PMID22971921
  5. Fukunaga-Kalabis M, Herlyn M. Cancer: complexion matters. Nature.2012;491:342-343.PMID23123853