FIRST-Funded Research Projects
FIRST has awarded $1.8 million in ichthyosis research funding since 2006
Evaluating novel therapeutic strategies for Darier disease - Cory Simpson - 2023
Darier disease is an incurable genetic skin disorder caused by impaired keratinocyte adhesion and cornification. Though linked to SERCA2 deficiency more than 20 years ago, there is still no FDA-approved treatment for this rare disease. Based on our recent work identifying hyper-activation of EGF receptor signaling in Darier disease, we will assess the therapeutic potential of inhibiting this pathway.
Functional consequences of keratin isoform switching during epidermal differentiation - Benjamin Nanes - 2023
In epidermolytic ichthyosis, mutations affecting keratin 1 (K1) or keratin (K10) disrupt the keratin mechanical scaffold. Understanding K1/10-specific functions that may not be rescued by other keratin isoforms expressed in epidermis is critical for many potential treatment strategies.
Inhibition of mutant connexin channels in KID Syndrome - Thomas W. White - 2022
Mutations in connexin26 (Cx26) that cause keratitis-ichthyosis-deafness (KID) syndrome have increased hemichannel activity. We will test inhibition of mutant hemichannels as a strategy to alleviate the skin pathology of KID syndrome in a mouse model.
To test inhibition of mutant connexin hemichannels as a new therapeutic approach in a mouse model that expresses the human Cx26-G45E KID syndrome mutation. These mice have increased hemichannel activity in keratinocytes. We hypothesize that inhibiting the acquired hemichannel activity will improve skin disease.
Darier disease drug screen - Jakob Wikström, MD, PhD - 2021
In this bench-to-bedside translational study for Darier Disease, we will establish a series of patient derived keratinocyte cell lines from DD patients, which will be used to screen pharmacological compounds likely to improve ER calcium homeostasis and ER stress. This study will select candidate compounds that will be tested in a future clinical trial. To enable this study, we have a unique clinical cohort of DD patients, and published experience in ER biology.
Interplay between the microbiota and skin homeostasis in Darier disease - Nan Ring, MD - 2021
Congrats to Nan Ring. Her project is a multidisciplinary project to investigate the role of the microbiota in Darier disease, with the ultimate goal of uncovering disease pathways that can be targeted for therapeutic purposes. Preliminary data suggest that overgrowth of S. aureus is associated with flares, while the skin microbiota of patients with well-controlled disease more closely resembles that of normal controls. As we continue the study, we look forward to learning more about the role of the microbiota in Darier disease, as well as the specific protein-protein interactions between implicated microbes and the human host. We ultimately hope to uncover druggable targets and create treatments that decrease morbidity and improve the quality of life of patients living with this inherited lifelong disease.