4/16/2023 0 Comments Mical syndromeThe cellular consequence is premature senescence, which contributes to the accelerated aging phenotype.īecause this mutation directs a dominant negative effect, it facilitated the generation of a humanized transgenic mouse model by inserting a human genomic DNA segment containing the LMNA gene engineered with the c.1824C/T mutation. The deletion of the 50 amino acids in the mutant progerin protein created by the cryptic splice mutation results in the permanent farnesylation of mature lamin A causing disruption of nuclear organization and chromatin structure. Normally, the LMNA gene precursor protein, prelamin A, is farnesylated prior to incorporation into the nuclear membrane, then cleaved by an endoprotease to release mature lamin A that is incorporated in the nuclear lamina matrix. In fact, HGPS can be seen as a textbook demonstration of the evolution of therapeutic advances for a rare disorder. Erdos and colleagues' lab discovered the dominant negative cryptic splice mutation, c.1824 C/T, in the LMNA gene generates the mutant progerin protein responsible for HGPS and causes a plethora of phenotypic consequences, including death from heart attack of stroke by the early teens. In the ultra-rare premature aging disorder HGPS, Dr. The application of genetic, genomic and functional biology approaches are valuable and increasingly powerful ways to provide understanding of both rare and complex diseases and of the potential for therapeutic development. In addition, he is a collaborator in the Accelerating Medicines Partnership in Type 2 Diabetes (AMP-T2D) consortium. Erdos is a senior investigator in the Finnish US Investigation of NIDDM (FUSION), non-insulin dependent diabetes mellitus (NIDDM) genetics study and in the Integrated Network for Systematic Analysis of Pancreatic Islet RNA Expression (InsPIRE) consortium. It was that work on T2D that led to the awarding of his Ph.D. That information can both provide predictive risk for disease prevention and point to optimal targets for development of potential therapeutic agents. Erdos is using multi-omics analyses to elucidate the impact and functional basis of risk variants for type 2 diabetes (T2D). In the context of complex genetic disease, Dr. Two of those treatment strategies are in the application process for FDA approval. Erdos conducts preclinical translational research to identify and validate potential therapeutics for the rare premature-aging disease, Hutchinson Gilford Progeria Syndrome (HGPS). In 1993, he moved to the NHGRI Intramural Research Program where he focused initially on the discovery and functional analysis of the BRCA1 gene.Ĭurrently, Dr. Erdos moved to the National Heart, Lung and Blood Institute in 1990 where he focused on IL2 receptor-associated kinase signaling and the search for the IL2Rg gene. Erdos studied circulating thymic peptides modulated by immune disorders and HIV at the George Washington University. Prior to arriving at the National Institutes of Health, Dr. Erdos focuses on translational research determining the effect of genetic variation on gene function and identifying primary targets for potential therapeutic development.
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