Thread by @JIDJournals

First State of the Art Lecture on Thursday was Isaac Brownell from the Dermatology Branch at @NIH_NIAMS, in a talk titled "Merkel cells and Merkel cell carcinoma: neuroendocrine skin cells from development to cancer" 1/n #sid2021

Merkel cells are innervated neuroendocrine cells, and they function as mechanical sensors. In mouse skin they actually cluster around specialized keratinocytes that are part of structure call the 'touch dome'
2/n #sid 2021

It turns out that sonic hedgehog signaling from sensory nerves is required to maintain that touch dome - this is a deep connection between the nervous system and keratinocytes
3/n #sid2021

Further experiments demonstrated that local sonic hedgehog signaling is critical for Merkel cell development, and so the recent focus has been exploring the stages of Merkel cell differentiation. They attack this with single cell RNAseq #sid2021 4/n

They show some beautiful unpublished data that clearly shows distinct phases of Merkel cell development - the transcriptional profiles align with the expected temporal dynamics of cell development, increasing confidence in the validity of their results! 5/n #sid2021

Next we shift to Merkel cell carcinoma (MCC), which is associated with age, immunosuppresion, and UV radiation. The connection to immunosuppression inspired Yuan Chang and Patrick Moore to suspect and discover a viral etiology for MCC (pubmed.ncbi.nlm.nih.gov/18202256/) #sid2021 6/n

80% of MCC is polyomavirus related, the remaining 20% is due to UV radiation, and in both cases treatment involves surgery and radiotherapy for early stage disease, and checkpoint inhibitor therapy for metastatic disease, with some patients showing excellent response #sid2021 7/n

However, >50% of patients do not benefit from checkpoint inhibitors with eventual progression, so one focus of the lab is to improve these responses and make new treatments. Could virus specific T cells be helpful? #sid2021 8/n

In a large drug screen, they were able to find some compounds that selectively killed virus positive and virus negative merkel cell carcinoma lines - in an interesting twist, Disulfuram was one of these compounds, an in poster 485 Natasha Hill dives into that story #sid2021 9/n

Beyond new compounds, their drug screen identified categories of treatment with likely on-target therapeutic effects. This gives insights into Merkel cell carcinoma pathogenesis and they are following up on multiple compounds #sid2021 10/n

For example, looking at why histone deacetylase inhibitors showed up on their screen, they discovered that the viral oncogene drives the production of antigens that bind neuroendocrine transcription factor super enhancer sites, thus forming a positive feedback loop #sid2021 11/n

This was an expansive talk with an impressive body of work including basic insights into Merkel cell development and new treatment avenues. He finishes with a plug for doing skin science at @NIH! #sid2021 12/12