Following up on prior work that identified the perineural microenvironment as a regulator of hair follicle stem cells, we have completed a project describing a perivascular niche for hair follicle stem cells. Moreover, we have identified that sensory touch domes in the skin, and the Merkel cells housed there are also regulated by associated Shh signaling from sensory neurons. We have continued experiments demonstrating that touch domes are a novel and distinct cell lineage within the skin maintained by their own stem cell population. We have also investigated the developmental requirements for Merkel cell formation in skin. We have found that establishing the Merkel cell touch dome lineage in embryonic skin requires a cascade of Wnt, Eda, and intraepithelial Shh signaling. Ongoing work using single cell RNA-seq and ATAC-seq investigates the transcriptional requirements for Merkel cell differentiation. These studies have identified neuroendocrine lineage factors that are important for both normal Merkel cell formation and are critical in Merkel cell carcinoma.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Baker, Mairead; Cordes, Lisa; Brownell, Isaac (2018) Avelumab: a new standard for treating metastatic Merkel cell carcinoma. Expert Rev Anticancer Ther 18:319-326
Gaiser, Maria Rita; Weis, Cleo-Aron; Gaiser, Timo et al. (2018) Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells. Oncoimmunology 7:e1426517
Brosseau, Jean-Philippe; Pichard, Dominique C; Legius, Eric H et al. (2018) The biology of cutaneous neurofibromas: Consensus recommendations for setting research priorities. Neurology 91:S14-S20
Kaufman, Howard L; Russell, Jeffery S; Hamid, Omid et al. (2018) Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ?1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer 6:7
Gaiser, Maria Rita; Bongiorno, Michelle; Brownell, Isaac (2018) PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma. Expert Rev Clin Pharmacol 11:345-359
Dasgeb, B; Kornreich, D; McGuinn, K et al. (2018) Colchicine: an ancient drug with novel applications. Br J Dermatol 178:350-356
Cassler, N M; Brownell, I (2017) PD-1 checkpoint blockade is an emerging treatment for Merkel cell carcinoma. Br J Dermatol 176:18
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
Barkdull, Savannah; Brownell, Isaac (2017) PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma. Cancer Biol Ther 18:937-939
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

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