We have previously identified a group of conserved noncoding elements (CNEs) in the EDC that demonstrate dynamic regulatory activity. Two CNEs, 621 and 923, exhibited epidermal-specific enhancer activity in transgenic reporter mice. CNE 621 mapped within a psoriasis copy number variant (LCE3C_LCE3Bdel) suggesting loss of regulatory activity in psoriasis. We are currently investigating a role for CNE923 as a locus control region (LCR) or “master switch” for EDC gene expression using experimental (molecular, biochemical) and bioinformatic approaches.
We have an ongoing interest in the role of methylation changes in cancer as well as the roles of androgen and estrogen receptor signaling in prostate and breast cancer. We demonstrated that in castration-resistant prostate cancer, androgen receptor signaling still plays a major role, but that the binding sites are substantially remodeled (Decker et al, 2012). Further we have shown that amplification of the estrogen-receptor is one potential mechanism amongst various mutations and fusions by which estrogen receptor is over-expressed in endocrine therapy resistant breast cancer (Li et al. 2013). Lastly, we mapped DNA methylation genome-wide in endocrine therapy resistant breast cancer and demonstrated that epigenetic activation of the EP4 receptor was required for estrogen-independent cell proliferation (Hiken et al. 2017).
Reprogramming DNA methylation using CRISPR/Cas9
Welcome! This resource page provides the information and resources needed to implement a CRISPR/Cas9-targeted DNA methyltransferase system for site-specific induction of DNA methylation. This project is a joint collaboration between the Edwards and Challen labs.
We have used the protocols and resources below to induce methylation and decrease gene expression as described in Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation.
Metagenomic Biomarkers for Chronic Itch
Chronic itch or pruritis that lasts more than 6 weeks is one of the most challenging diseases to manage in the clinic. Current anti-pruritic treatments are largely ineffective and this is a reflection of our lack of understanding of the pathophysiology of itch. To date, very little is known about the epicutaneous, molecular markers associated with chronic itch severity in humans.
The tight comorbidity of chronic itch to common inflammatory skin diseases, atopic dermatitis (AD), allergic contact dermatitis (ACD), and psoriasis, provides a unique opportunity to directly investigate epicutaneous, molecular biomarkers in humans. We hypothesize that molecular biomarkers for chronic itch are defined as a set of transcriptional units (both messenger and micro RNAs) and resident bacteria that are upregulated and shared in skin lesions that chronically itch. We are currently using metagenomics to identify the biomarkers.