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BEDMINSTER, N.J., Feb. 25, 2021 /PRNewswire/ Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, today announced a collaboration with Boston Children s Hospital (https://wistar.org/) to evaluate peptidyl arginine deiminase 4 (PAD4) inhibitors under development by Jubilant Therapeutics to explore the modulation of neutrophil extracellular traps (NETosis) in preclinical models of neutrophil regulation and rheumatoid arthritis (RA).
PAD4 is an enzyme that converts arginine to citrulline in histones and is highly expressed in neutrophils. Histone citrullination has been implicated in the formation of NETs which is believed to contribute to pro-inflammation and disease progression in many autoimmune disorders including RA, fibrosis, lupus and ARDS.
Researchers in the laboratory of Frederick Alt of the Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine (PCMM) at Children’s Hospital Boston made a groundbreaking discovery at the nexus of chromatin biology and immunology. Their work, recently published in Nature, showed that physiological deregulation of the WAPL chromatin-maintenance factor allows developing B lymphocytes to scan linearly through very long chromosomal loops to find and join gene segments that form diverse antibody repertoires.
Recently the Alt group discovered that V(D)J recombination and IgH class switch recombination (CSR), two discrete mechanisms of programmed genetic rearrangement in lymphocytes, both critical for adaptive immunity, are mechanistically driven by a basic process associated with management of the architecture of chromosomal genomes: chromatin loop extrusion (“Chromatin loops unlock antibody class switching”).