John M. Pawelek, PhD

Senior Research Scientist
Department of Dermatology & Pharmacology

Research Interests

1. Tumor cell fusion with bone marrow-derived cells as a cause of melanoma metastasis.

2. Aberrant glycosylation in melanoma and its relation to metastasis.

Education:	AB, Gettysburg College, 1963 PhD, Brown University, 1967
Training:	Fellowship: Yale University

Selected Publications

• Chakraborty AK, Pawelek JM. Beta1, 6-branched oligosaccharides regulate melanin content and motility in macrophage-melanoma fusion hybrids. Melanoma Res, 17: 9-16, 2007.
• Handerson T, Berger A, Harigopol M, Rimm D, Chikako N, Ueda M, Miyoshi E, Taniguchi N, Pawelek J. Melanophages reside in hypermelanotic, aberrantly glycosylated tumor areas and predict improved outcome in primary CMM. J. Cutaneous Pathol, 34: 667-738, 2007.
• Pawelek J. Viewing malignant melanoma cells as macrophage-tumor hybrids. Cell Adhesion and Migration 1:2-6, 2007.
• Chakraborty AK, de Frietas Sousa J, Chakraborty D, Funasaka Y, Bhattacharya M, Chatterjee A, Pawelek J. GnT-V expression and metastatic phenotypes in macrophage-melanoma fusion hybrids is down-regulated by 5-Aza-dC: Evidence for methylation sensitive, extragenic regulation of GnT-V transcription. Gene. 2006 Mar 21; [Epub ahead of print]
• Pawelek J, Chakraborty A, Lazova R, Yilmaz Y, Cooper D, brash D, Handerson T, Co-Opting Macrophage Traits in Cancer Progression: A Consequence of Tumor Cell Fusion? Contrib Microbiol. 13:138-155, 2006.
• Handerson, T., Camp, R., Harigopal, M., Rimm, D., and Pawelek, J. ßi-Branched oligosaccharides are associated with metastasis and predict poor outcome in breast carcinoma. Clin. Can. Res. 11: 2969-2973, 2005.
• Yillmaz, Y., Lazova, R., Qumsiyeh, M., Cooper, D., and Pawelek, J. Donor Y chromosome in renal carcinoma cells of a female BMT recipient. Bone Marrow Transplant 35:1021-1024, 2005.
• Siddiqui SF, Pawelek J, Handerson T, Lin CY, Dickson RB, Rimm DL, Camp RL. Coexpression of beta1,6-N-acetylglucosaminyltransferase V glycoprotein substrates defines aggressive breast cancers with poor outcome. Cancer Epidemiol Biomarkers Prev. 14:2517-2523, 2005.
• Pawelek, J. Tumor cell fusion as a source of myeloid traits in cancer. The Lancet Onclogy 6: 988-993, 2005. (accompanying commentary: Friedl P. Cell fusion: new mechanisms of plasticity in cancer? Lancet Oncol. 2005;12:916-918.)
• Pawelek J. Tumor cell fusion as a source of myeloid traits in cancer. The Lancent Oncology 6: 988-993,2005.
• Rupani, R., Handerson, T., and Pawelek, J. Co-localization of ß1,6-branched oligosaccharides and coarse melanin in macrophage-melanoma fusion hybrids and human melanoma cells in vitro. Pigment Cell Res. 17: 281-288, 2004.
• Chakraborty, A., Lazova, R., Davies, S., Bäckvall, H., Ponten, F., Brash, D., and Pawelek, J. Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient. Bone Marrow Transplantation 34: 183-186, 2004.
• Chakraborty, A.K. and Pawelek, J.M. GNT-V, macrophages, and cancer metastasis: A common link. Clin. Exp. Metastasis 20: 365-373, 2003.
• Handerson, T., and Pawelek, J. ß1,6-branched oligosaccharides and coarse vesicles: A common and pervasive phenotype in melanoma and other human cancers. Cancer Res. 63: 5363-5369, 2003.
• Pawelek, J., Low, K.B., and Bermudes, D. Bacteria as tumour-targeting vectors. Lancet Oncol. 4 (9): 548-556, 2003.
• Chakraborty, A.K., Kolesnikova, N., de Freitas Sousa, J., Espreafico, E.M., Chagas Peronni, K., and Pawelek, J. Expression of c-met proto-oncogene in metastatic macrophage x melanoma fusion hybrids: Implication of its possible role in MSH-induced motility. Oncol. Res. 14: 163-174, 2003.
• Pawelek JM, Sodi S, Chakraborty AK, Platt JT, Miller S, Holden DW, Hensel M, Low KB. Salmonella pathogenicity island-2 and anticancer activity in mice. Cancer Gene Ther.10: 813-818, 2002.
• Chakraborty, A,K., Pawelek, J.M, Ikeda, Y., Miyoshi, E., Kolesnikova, N., Funasaka, Y., Ichihashi, M., and Tanaguchi, N. Macrophage fusion up-regulates N-acetyl-glucosaminyltransferase V, ßi branching, and metastasis in Cloudman S91 mouse melanoma cells. Cell Growth and Differentiation 12: 623-630, 2001.
• Chakraborty AK, de Freitas Sousa J, Espreafico EM, Pawelek JM. Human monocyte x mouse melanoma fusion hybrids express human gene. Gene 275:103-6, 2001.
• Chakraborty, A., Sodi, S., Rachkovsky, M., Kolesnikova, N., Platt, J., Bolognia, J. and Pawelek, J. A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids. Cancer Research 60: 2512-2519, 2000.
• Platt, J., Sodi, S., Kelley, M., Rockwell, S., Bermudes, D., Low, K.B., and Pawelek, J. Antitumor effects of genetically engineered Salmonella in combination with radiation. Eur. J. Cancer 36: 2397-2402, 2000.
• Clairmont, C., Lee, K.C., Pike, J., Ittensohn, M., Low, K.B., Pawelek, J., Bermudes, D., Brecher, S.M., Margitich, D., Turnier, J., Li, Z., Luo, X., King, I., and Zheng, L.M. Biodistribution and genetic stability of the novel antitumor agent VNP20009, a genetically modified strain of Salmonella typhimurium. J. Infect. Diseases 181: 1996-2002, 2000.
• Araki, K., Horikawa, T., Chakraborty, A.K., Nakagawa, K., Itoh, H., Oka, M., Funasaka, Y., Pawelek, J., Ichihashi, M. Small GTPase RAB3A is associated with melanosomes in melanoma cells. Pigment Cell Res 13(5): 332-336, 2000.
• Bermudes D, Low B, and Pawelek J. Tumor-Targeted Salmonella: Strain development and expression of the HSV TK effector gene. In: Gene Therapy of Cancer: Methods and Protocols, W. Walther and U. Stein (eds), Humana Press,Totowa, NJ, Vol 35: 419-436, 2000.
• Pawelek JM, Chakraborty AK, Rachkovsky ML, Orlow SJ, Bolognia JL, and Sodi SA. Altered N-glycosylation in macrophage x melanoma fusion hybrids. Cell Mol Biol, in press, 2000.
• Low, K.B. Ittensohn, M., Le T., Platt, J., Sodi, S., Amoss, M., Ash, O., Carmichael, E., Chakraborty, A., Fischer, J., Lin, S.L., Luo, X., Miller, S.I., Zheng, L-m., King, I., Pawelek, J.M., and Bermudes, D. Lipid A mutant Salmonella with suppressed virulence and TNF induction retain tumor-targeting in vivo. Nature Biotechnology 17: 37-41, 1999.
• Chakraborty, A.K., Funasaka, Y., Ichihashi, M., Sodi, S., Bhattacharya, M., and Pawelek, J. Upregulation of mRNA for the melanocortin-1 receptor but not for melanogenic proteins in macrophage x melanoma fushion hybrids exhibiting increased melanogenic and metastatic potential. Pig. Cell Res. 12: 355-366, 1999.
• Rachkovsky M, Pawelek J. Acquired Melanocyte Stimulating Hormone-inducible Chemotaxis following macrophage Fusion with Cloudman S91 Melanoma Cells. Cell Growth & Differ. 10: 517-24, 1999.
• Bermudes D, Low B, and Pawelek J. Tumor-targeted Salmonella: Highly selective delivery vectors. In Cancer Gene Therapy: Past Achievements and future challenges, N. Habib (ed), Plenum Press 75-63, 1999.
• Funasaka Y. Chakraborty AK, Hayashi S. Komoto M, Ohashi A, Nagahama M, Inoue T. Pawelek J. and Ichihashi M. Modulation of melanocyte stimulating hormone receptor expression on normal human melanocytes: Evidence for a regulatory role of UVB, IL-la, IL-lb, ET-1, and TNFa. Br J Dermatol in press, 1998, August issue.
• Rachkovsky MS, Sodi S. Chakraborty A, Avissar Y. Bolognia J. Madison J. Bermudes D, and Pawelek J. Enhanced metastatic potential of melanoma x macrophage fusion hybrids. J Clin Exp Metastasis 16:299-312, 1998.
• Rachkovsky MS, Sodi S, Chakraborty A, Avissar Y, Bolognia J, Madison J, Bermudes D, and Pawelek J. Enhanced metastatic potential of melanoma x macrophage fusion hybrids. Clin Exp Metastasis 16: 299-312, 1998.
• Sodi S.A., Chakraborty A.K., Platt J.T., Kolesnikova, N., Rosemblat, S., Keh-Yen, A., Bolognia, J.L., Rachkovsky, M.L., Orlow, S.J., and Pawelek, J.M. Melanoma x macrophage fusion hybrids acquire increased melanogenesis and metastatic potential: Altered N-glycosylation as an underlying mechanism. Pigment Cell Res. 11: 299-309, 1998.
• Pawelek, J.M. MelaSynTM: A new self-tanner with sun protective qualities. DCI 163: 28-33, Oct. 1998.
• Pawelek J and Chakraborty AK. The Enzymology of Melanogenesis in The Pigmentary System and Its Disorders (eds. Nordland JJ, Boissy RE, Hearing VJ, King RA, and Ortonne JP) Oxford University Press 391-400, 1998.
• Slominski A and Pawelek J. Animals under the sun: effects of UV radiation on mammalian skin. In Clinics in Dermatology, Elsevier Science 16:503-515, 1998.
• Pawelek J. Low KB, and Bermudes D. Tumor-targeted Salmonella as a novel anti-cancer vector. Cancer Res 57:4537-4544, 1997.
• Chakraborty AK, Platt JT, Kim KK, Kwon BS, Bennett DC, and Pawelek JM. Superoxide-dependent polymerization of DHICA to melanin by the si (silver) locus protein, PMEL-17. Eur J Biochem 236:180-188, 1996.
• Chakraborty AK, Funasaka Y. Slominski A, Ermak G. Hwang J. Pawelek JM, and Ichihashi M. Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: regulation by ultraviolet B. BBA, 1313:130-138, 1996.
• Slominski A, Baker J. Ermak G. Chakraborty A, and Pawelek J. Ultraviolet B stimulates production of corticotropin releasing factor (CRF) by human melanocytes. FEBS Letters 399:175-176, 1996.

Book Chapters/Review

• Pawelek J, Chakraborty A, Lazova R, Yilmaz Y, Cooper D, Brash D, Handerson T. Co-Opting Macrophage Traits in Cancer Progression: A Consequence of Tumor Cell Fusion? Contrib Microbiol. 2006;13:138-155.
• Low, K.B., Ittenshohn, M., Luo, X., Zheng, L.M., King, I., Pawelek, J.M., and Bermudes, D. Construction of VNP20009: a novel, genetically stable antibiotic-sensitive strain of tumor-targeting Salmonella for parenteral administration in humans. Methods Mol Med. 90: 47-60, 2004.
• Pawelek, J.M. Review - Innovative Technology: Approaches to Increasing Skin Melanin with MSH Analogs and Synthetic Melanins. Pigment Cell Res. 14: 155-160, 2001.
• Bermudes, D., Low, K.B., Pawelek, J., Sznol, M., Belcourt, M., Zheng, L-m, and King, I. Tumor-specific Salmonella-based cancer therapy. Stephen E. Harding (ed) Biotechnology and Genetic Engineering Rev. 18: 219-233, 2001.
• Pawelek, J.M. Tumor Cell Hybridization and Metastasis Revisited. Melanoma Res. 10: 507-514, 2000.
• Chakraborty AK, Funasaka Y, Slominski A, Bolognia J, Sodi S, Ichihashi M, Pawelek JM. UV light and MSH receptors. Ann N Y Acad Sci. 1999;885:100-16.
• Slominski A and Pawelek J. Animals under the sun: effects of UV radiation on mammalian skin. Clinics in Dermatol. 16: 503-515, 1998.

Awards

• Outstanding Alumnus Award, Gettysburg College, Gettysburg, Pennsylvania 1999 Career Achievement Award, Pan American Society for Pigment Cell Research, 2000.

Cirriculum Vitae

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Contact

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

Phone
(203) 785-4092

E-mail
john.pawelek@yale.edu