Ruth Halaban, Ph.D

Senior Research Scientist, Department of Dermatology

Research Interests

Genes controlling differentiation, proliferation and malignant transformation of melanocytes, growth factors and receptor kinases, signal transduction.

Education:	B.Sc., 1962, Hebrew University M.Sc, 1964, Hebrew University Ph.D., 1968, Princeton University
Training:	Fellowship: Brookhaven National Laboratory, SUNY at Albany

Selected Publications

• Bõhm M, Moellmann G, Cheng E, Alvarez-Franco M, Wagner S, Sassone-Corsi P, Halaban R: Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Cell Growth Differ 6:291-302, 1995
• Kwon BS, Halaban R, Ponnazhagan S, Kim K, Chintamaneni C, Bennett D, Pickard RT: Mouse silver mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17. Nucleic Acids Res 23:154-158, 1995
• Halaban R, Bõhm M, Dotto P, Moellmann G, Cheng E, Zhang YH: Growth regulatory proteins that repress differentiation markers in melanocytes also downregulate the transcription factor Microphthalmia. J Invest Dermatol 106:1266-1272, 1996
• Lee ZH, Hou L, Moellmann G, Kuklinska E, Antol K, Fraser M, Halaban R, Kwon BS: Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6,-dihydroxyindole-2-carboxylic acid (DHICA) converting activity. J Invest Dermatol 106:605-610, 1996
• Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL: UV-induced ubiquitination of RNA polymerase II - a novel modification deficient in Cockayne syndrome cells. Proc Natl Acad Sci USA 93:11586-11590, 1996
• Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert DN: Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc Natl Acad Sci USA 94:6210-6215, 1997
• Longley BJ, Tyrrell L, Ma Y, Williams DA, Halaban R, Langley K, Lu HS, Schechter NM: Chymase cleavage of stem cell factor yields a bioactive, soluble product. Proc Natl Acad Sci USA 94:9017-9021, 1997
• Yayon A, Ma YS, Safran M, Klagsbrun M, Halaban R: Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src- family kinases. Oncogene 14:2999-3009, 1997
• Fargnoli MC, Edelson RL, Berger CL, Chimenti S, Couture C, Mustelin T, Halaban R: Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk. Leukemia 11:1338-1346, 1997
• Miglarese MR, Halaban R, Gibson NW: Regulation of FGF-2 expression in melanoma cells by the c-Myb proto-oncoprotein. Cell Growth Differ 8:1199-1210, 1997
• Watson ML, Zinn AR, Inous N, Hess KD, Cobb J, Handel MA, Halaban R, Duchene CC, Albright GM, Moreadith RW: Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse. Proc Natl Acad Sci USA 95:14361-14366, 1998.
• Halaban R, Cheng E, Zhang Y, Mandigo CE and Miglarese MR: Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by delation of p16INK4A or p21WAF1/CIP1. Oncogene 16: 2489-1501, 1998.
• Halaban R, Cheng E, Zhang Y, Mandigo CE, Miglarese MR: Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene 16:2489-2501, 1998

Reviews, Chapters

• Halaban R: Growth factors and melanomas [Review]. Sem Oncol 23:673-681, 1996
• Halaban R, Miglarese MR, Smicun Y, Puig S: Melanomas, from the cell cycle point of view (Review). Int J Mol Med 1:419-425, 1998
• Moellmann G, Halaban R. Growth-factor receptors and signal transduction regulating the proliferation and differentiation of melanocytes. New York: Oxford University Press, New York. 1998; Chapter 10, pp135-149
• Halaban R, vonWillebrand-Backman MC. Signal transduction abnormalities as therapeutic targets. In Melanoma: Translating Biological into Effective Therapy, vol. in press. E.C. Borden, editor. Humana Press Inc, Torowa, NJ, 2000.
• Halaban R, Svedine S, Cheng E, Smicun Y, Aron R, Hebert DN. Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proc Natl Acad Sci USA 97: 5889-94, 2000.
• Halaban R, Cheng C, Smicun Y, Germino J. Deregulated E2F transcriptional activity in autonomously growing melanoma cells. J Exp Med 191:1005-15, 2000
• Halaban R, Patton RS, Cheng E, Svedine S, Trombetta ES, Wahl ML, Ariyan S, and Hebert DN. Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway. J Biol Chem 2002;277: 14821-14828.
• Halaban R, Cheng E, and Hebert DN. Co-expression of wild type tyrosinase enhances maturation of temperature-sensitive tyrosinase mutants. J Invest Dermatol 2002;119: 481-488.
• Halaban R, Cheng E, Svedine S, Aron R, and Hebert DN. Proper folding and ER to Golgi transport of tyrosinase are induced by its substrates, DOPA and tyrosine. J Biol Chem 2001;276: 11933-11938.
• Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, and Rimm DL. Subcellular localization of activating transcription factor 2 (ATF2) in melanoma specimens predicts patient survival. Cancer Res 2003;63: 8103–8107.
• Francis E, Wang N, Parag H, Halaban R, and Hebert DN. Tyrosinase maturation and oligomerization in the endoplasmic reticulum require a melanocyte-specific factor. J Biol Chem 2003;278: 25607-25617.
• von Willebrand M, Zacksenhaus E, Cheng E, Glazer P, and Halaban R. The tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells. Cancer Res 2003;63: 1420-1429.
• Berger AJ, Camp RL, DiVito KA, Kluger HM, Halaban R, Rimm DL. Automated quantitative analysis (AQUA) of HDM2 expression in malignant melanoma shows association with early stage disease and improved outcome. Cancer Res 2004; 64: 8767-72.
• Kluger HM, DiVito K, Berger AJ, Halaban R, Ariyan S, Camp RL, and Rimm DL. Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res 2004;14: 207-210.
• Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, E. Trombetta S, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res 2004;64: 5270–5282.
• Angeletti C, Khomitch V, Halaban R, and Rimm DL. Novel tyramide-based tyrosinase assay for the detection of melanoma cells in cytological preparations. Diagn Cytopathol 2004;31: 33-37.
• Kluger Y, Tuck DP, Chang JT, Nakayama Y, Poddar R, Kohya N, Lian Z, Ben Nasr A, Halaban R, Krause DS, Zhang X, Newburger PE, and Weissman SM. Lineage specificity of gene expression patterns. Proc Natl Acad Sci USA 2004;101: 6508-6513.
• Kluger HM, DiVito K, Berger AJ, Halaban R, Ariyan S, Camp RL, Rimm DL. Her2/neu is not a commonly expressed therapeutic target in melanoma – a large cohort tissue microarray study. Melanoma Res 2004;14: 207-210.

Contact

Campus Address
Yale School of Medicine
333 Cedar Street
New Haven, CT 06520-8059

Email
ruth.halaban@yale.edu

Office Phone
(203) 785-4352