Maroof Hasan
Novartis Institutes for BioMedical Research, Switzerland
Posters & Accepted Abstracts: Immunome Res
The functional and molecular integration between immune and metabolic system is crucial for homeostasis of an organism. Defective immunometabolism has been implicated in many aspect of biology including cancer, autoimmune and infectious diseases although the underlying mechanisms remain largely elusive. TREX1 is an endoplasmic reticulum (ER)- associated exonuclease that digests viral or host DNA in the cytosol and prevent accumulation and activation of cytoplasmic DNA sensing pathway. TREX1 mutations are associated with a broad spectrum of autoimmune and inflammatory phenotypes, including Aicardi-Goutieres syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus (SLE) and retinal vasculopathy with cerebral leukodystrophy (RVCL). Recently, we discovered that TREX1 regulates lysosomal biogenesis through a mechanism involving master regulator of cellular metabolism, mTORC1. Using various TREX1 mutant/truncation constructs and also animal models, we have identified the molecular cause that is associated with TREX1-deficiency/mutations. We also identified unique pathomechanisms associated with RVCL due to misregulated oligosaccharyl transferase (OST) activity and glycan metabolism. Most importantly, we identified target specific small molecule inhibitors for the treatment of TREX1 associated autoimmune diseases and potential other interferonopathies.
Email: maroof.hasan@novartis.com
