The answers to some of medicine’s most challenging questions are often written in our genes. The PROPA Lab is dedicated to deciphering this genetic code to understand the root causes of rare genetic disorders and neurodevelopmental syndromes. Our mission is to uncover the specific genetic variants that disrupt normal physiological function, providing clarity for patients and paving the way for new therapies.
We employ a comprehensive, multi-omics strategy to gain a holistic view of the genetic basis of disease:
- Functional Genomics & Whole-Exome Sequencing: We start by sequencing the protein-coding regions of the genome (the exome) in patients and families to pinpoint potential disease-causing mutations.
- Integrative Multi-Omics Profiling: We don’t work in a single dimension. We layer genomic data with transcriptomic (gene expression) and epigenetic (gene regulation) information. This integrated profile allows us to see not just the genetic variant, but its functional consequences on cellular processes.
Research Focus and Impact
Our research in medical genetics focuses on identifying the molecular and genetic basis of hereditary disorders, particularly in consanguineous families, using whole-exome sequencing, segregation analysis, and protein-level interpretation. We have identified pathogenic and likely pathogenic variants underlying a range of inherited conditions, including ichthyosis, tooth agenesis, hearing impairment, and syndromic metabolic disorders. These studies have uncovered disease-causing variants in genes such as FLG, TGM1, STS, RFX2, PSAP, ADAMTS1, MPDZ, MVD, SEZ6, CDK13, and REST, expanding the mutational and phenotypic spectrum of several rare genetic disorders.
In addition, we investigate population-specific genetic variation and its functional consequences, with particular attention to single-nucleotide polymorphisms and missense variants affecting protein structure and function. Our work includes the characterization of ABCC1 (MRP1) polymorphisms in type 2 diabetes, revealing novel variants with predicted structural effects on drug transport and metabolism. By integrating genomic data with computational protein modeling and clinical phenotyping, our research supports variant interpretation, genetic counseling, and mechanism-driven understanding of inherited diseases relevant to precision medicine.