WILLIAM MONTAGNA LECTURE
Hedgehog signaling in skin biology and tumorigenesis: where, when, and how?
Andrzej A. Dlugosz MD
Dr. Dlugosz is both Professor of Cutaneous Oncology and Professor in the Departments of Dermatology and Cell & Developmental Biology at the University of Michigan. He is Director of the Cancer Biology Program in Dermatology and Co-director of the Cancer Cell Biology Program at the University of Michigan Comprehensive Cancer Center. He received his BA from Franklin and Marshall College, MD from Penn State, and completed a dermatology residency at the University of Pennsylvania. He did post-doctoral training at the NCI in Dr. Stuart Yuspa’s laboratory. Dr. Dlugosz’s honors include the Marion B. Sulzberger, MD, Memorial Award and Lectureship and election to the American Society for Clinical Investigation and the Association of American Physicians. His research has centered on defining the functions of the Hedgehog signaling pathway in hair follicle biology and tumorigenesis, with a major emphasis on basal cell carcinoma (BCC). Dr. Dlugosz’s work has helped establish a central role for deregulated Hedgehog signaling in BCC initiation and maintenance; defined a critical interaction between the Hedgehog and Wnt pathways in tumorigenesis; and elucidated the importance of cell of origin, timing of oncogene activation, and magnitude of Hedgehog signaling as key determinants of tumor phenotype.
Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson EK, Cooper MK, Gaffield W, Westphal H, Beachy PA, Dlugosz AA. Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev Biol. 1999 Jan 1; 205(1):1-9.
Grachtchouk M, Mo R, Yu S, Zhang X, Sasaki H, Hui CC, Dlugosz AA. Basal cell carcinomas in mice overexpressing Gli2 in skin. Nat Genet. 2000 Mar; 24(3):216-7.
Grachtchouk V, Grachtchouk M, Lowe L, Johnson T, Wei L, Wang A, de Sauvage F, Dlugosz AA. The magnitude of hedgehog signaling activity defines skin tumor phenotype. EMBO J. 2003 Jun 2; 22(11):2741-51. PMCID: PMC156767.
Allen M, Grachtchouk M, Sheng H, Grachtchouk V, Wang A, Wei L, Liu J, Ramirez A, Metzger D, Chambon P, Jorcano J, Dlugosz AA. Hedgehog signaling regulates sebaceous gland development. Am J Pathol. 2003 Dec; 163(6):2173-8. PMCID: PMC1892397.
Hutchin ME, Kariapper MS, Grachtchouk M, Wang A, Wei L, Cummings D, Liu J, Michael LE, Glick A, Dlugosz AA. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev. 2005 Jan 15; 19(2):214-23. Epub 2004 Dec 29. PMCID: PMC545881.
Grachtchouk M, Liu J, Wang A, Wei L, Bichakjian CK, Garlick J, Paulino AF, Giordano T, Dlugosz AA. Odontogenic keratocysts arise from quiescent epithelial rests and are associated with deregulated hedgehog signaling in mice and humans. Am J Pathol. 2006 Sep; 169(3):806-14. PMCID: PMC1698812.
Michael LE, Westerman BA, Ermilov AN, Wang A, Ferris J, Liu J, Blom M, Ellison DW, van Lohuizen M, Dlugosz AA. Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion. Neoplasia. 2008 Dec; 10(12):1343-9, 5p following 1349. PMCID: PMC2586685.
Yang SH, Andl T, Grachtchouk V, Wang A, Liu J, Syu LJ, Ferris J, Wang TS, Glick AB, Millar SE, Dlugosz AA. Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta-catenin signaling. Nat Genet. 2008 Sep; 40(9):1130-5. doi: 10.1038/ng.192. PMCID: PMC2688690.
Ames HM, Bichakjian CK, Liu GY, Oravecz-Wilson KI, Fullen DR, Verhaegen ME, Johnson TM, Dlugosz AA, Ross TS. Huntingtin-interacting protein 1: a Merkel cell carcinoma marker that interacts with c-Kit. J Invest Dermatol. 2011 Oct; 131(10):2113-20. doi: 10.1038/jid.2011.171. Epub 2011 Jun 23. PMCID: PMC3174286.
Grachtchouk M, Pero J, Yang SH, Ermilov AN, Michael LE, Wang A, Wilbert D, Patel RM, Ferris J, Diener J, Allen M, Lim S, Syu LJ, Verhaegen M, Dlugosz AA. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations. J Clin Invest. 2011 May; 121(5):1768-81. doi:10.1172/JCI46307. Epub 2011 Apr 25. PMCID: PMC3083781.