STATEMENT OF RESEARCH
I am a cancer biologist and Japanese board-certified dermatologist. My overall 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 disease still 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
only prevent 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 ultravioletinduced 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 melanocytes J 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, Herlyn M. 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 subpopulation of
slow-cycling melanoma cells is required for continuous 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 cotargeting 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, FukunagaKalabis 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, Vultur A, 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;4:10901099. 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-Peer Reviewed:
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