To identify genetic alterations present in Merkel cell carcinoma, we have conducted molecular analyses of human tumors and cancer cell lines across multiple genome-wide platforms to assay gene expression, identify gene mutations, and characterize chromosomal alterations. These data are being analyzed to identify key driver alterations for this tumor. We are also generating mice where oncogenic modifications are carried out in specific skin lineages in an attempt to transform Merkel cells in vivo. In addition, we are developing and characterizing cancer cell lines of Merkel cell carcinoma for in vitro and xenograft studies. We are also developing clinical biomarkers for Merkel cell carcinoma. Finally, we are conducting high throughput small molecule and genetic knockdown screens to identify pathways important for tumor survival and identify novel treatments for Merkel cell carcinoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011394-08
Application #
9779886
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Carroll, Thomas M; Williams, Jonathan S; Daily, Kenneth et al. (2017) Hedgehog Signaling Inhibitors Fail to Reduce Merkel Cell Carcinoma Viability. J Invest Dermatol 137:1187-1190
Eid, Mary; Nguyen, Jannett; Brownell, Isaac (2017) Seeking Standards for the Detection of Merkel Cell Polyomavirus and its Clinical Significance. J Invest Dermatol 137:797-799
Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K et al. (2016) Merkel Cell Carcinoma Therapeutic Update. Curr Treat Options Oncol 17:36
Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F et al. (2015) Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma. Mod Pathol 28:1023-32
Gaiser, Maria Rita; Daily, Kenneth; Hoffmann, Jochen et al. (2015) Evaluating blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers. Oncotarget 6:26472-82
Daily, Kenneth; Coxon, Amy; Williams, Jonathan S et al. (2015) Assessment of cancer cell line representativeness using microarrays for Merkel cell carcinoma. J Invest Dermatol 135:1138-1146
Geeraert, Pieter; Williams, Jonathan S; Brownell, Isaac (2013) Targeting the hedgehog pathway to treat basal cell carcinoma. J Drugs Dermatol 12:519-23