Gaurav choudhary biography of albert einstein
Gaurav CHOUDHARY, Research Fellow | Cited by | of Albert Einstein College of Medicine, New York City (AECOM) | Read 56 publications | Contact Gaurav.
Clinical scientist with 12+ years of experience in preclinical and clinical development within the field of oncology, contributing to 35 peer-reviewed.!
Abstract
Background:
Mutations in the SF3B1 splicing factor are commonly seen in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet the specific oncogenic pathways activated by mis-splicing have not been fully elucidated.
Inflammatory immune pathways have been shown to play roles in the pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood.
Methods:
RNA-seq data from SF3B1 mutant samples was analyzed and functional roles of interleukin-1 receptor-associated kinase 4 (IRAK4) isoforms were determined.
Efficacy of IRAK4 inhibition was evaluated in preclinical models of MDS/AML.
Results:
RNA-seq splicing analysis of SF3B1 mutant MDS samples revealed retention of full-length exon 6 of IRAK4, a critical downstream mediator that links the Myddosome to inflammatory NF-kB activation.
Exon 6 retention leads to a longer isoform, encoding a protein (IRAK4-long) that contains the entire dea