The Epidermis as a Novel Therapeutic Target in Pemphigus Vulgaris

By profiling genetic and molecular drivers of pemphigus vulgaris across patient skin and blood, this project uncovers genotype-driven inflammatory loops and actionable targets for personalized therapy.
Ongoing Dermatologic Diseases Pemphigus & Pemphigoid Animal Models Autoantibodies Biological & Mechanistic Cytokine Signaling Data-Driven & Quantitative Disease Subtyping Experimental Platforms & Models Human Cohorts Human Genetics Machine Learning & AI Multi-omics Integration Precision Medicine Therapeutic Development Translational & Clinical

Funding Year: 2023

Project Overview

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease driven by immune attacks on the skin, but its precise molecular causes remain incompletely understood. This project analyzes skin biopsies and blood samples from PV patients using advanced genomic technologies to compare gene expression patterns and map pathological changes at both the tissue and systemic levels. Natural language models are applied to patient records to extract detailed clinical data, which is integrated with molecular findings to build a comprehensive picture of disease. Functional assays and mouse models validate candidate therapeutic targets, with the goal of translating molecular discoveries — including newly identified risk variants in TRAV19 and ST18 — into actionable, personalized treatment strategies for PV

Impact & Innovation

A genotype-driven window into pemphigus vulgaris.

 

TRAV19 and ST18 risk variants create self-reinforcing inflammatory loops in PV — linking immune activation, keratinocyte signaling, and EGFR pathways into a novel, targetable disease mechanism.

  • Identifies specific genetic variants driving sustained PV pathogenesis, establishing new mechanistic targets for intervention
  • Generates IP potential through genotype-specific diagnostics and therapeutics applicable beyond PV
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar by connecting genotype-driven immune dysregulation to broader autoimmune convergences
Research Approach

A framework designed for discovery

This project integrates multi-omic profiling, computational analysis, and functional validation to identify and characterize the genetic and molecular mechanisms driving pemphigus vulgaris. The approach combines patient-derived tissue and blood data with mouse models and functional assays to move from discovery to therapeutic target validation.


Advanced genomic and transcriptomic profiling of PV patient skin biopsies and blood samples, natural language model-based extraction of clinical data from patient records, functional assays to validate candidate targets, and mouse models to assess disease-relevant mechanisms in vivo.

Skin biopsy and blood sample datasets from PV patients, gene expression profiling of PV-related genes at tissue and systemic levels, patient medical records processed via NLMs, and in vitro and in vivo functional validation datasets including keratinocyte assays and mouse models of PV.

Identification of genotype-driven disease mechanisms — specifically TRAV19 and ST18 risk variants — and their downstream inflammatory pathways, with the goal of defining actionable therapeutic targets for personalized treatment strategies in pemphigus vulgaris.

Investigators & Institutions

Powering the science

Principal Investigator

Eli Sprecher, MD, PhD, Colton Consortium Member

Professor, Dermatology, Gray Faculty of Medical and Health Sciences, Tel Aviv University

Key Collaborators

Noam Shomron, PhD, Colton Consortium Member

Professor, Gray Faculty of Medical and Health Sciences (Cell & Developmental Biology), Tel Aviv University

Tzachi Hagai, PhD

Professor, The Shmunis School of Biomedicine and Cancer Research Faculty of Life Sciences

Nachum Dershowitz, PhD

Professor Emeritus in School of Computer Science and AI

Colton Centers & Institutions

Colton Center for Autoimmunity at Tel Aviv University

Tel Aviv Sourasky Medical Center