Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:Myeloid-derived suppressor cells (MDSC) are potent negative regulators of immune responses at many pathological conditions. It is widely accepted that these cells are not present under steady state condition. Here, we report that MDSC with highly potent ability to suppress T cells accumulate during first two weeks of life in mice. MDSC suppressive activity in neonates was triggered by lactoferrin, a component of milk, and mediated by nitric oxide and up-regulation of PGE2 regulated by S100A9/A8 proteins. Newborn MDSC had transcriptome similar to that of tumor MDSC. However, they had strong up-regulation of antimicrobial gene network. This was associated with enhanced antimicrobial activity of these cells. MDSC played a critical role in control of experimental necrotizing enterocolitis in newborn mice. In humans, MDSC in cord blood of low-weight preterm infants prone to the development of NEC had significantly lower suppressive activity than the cells from cord blood of infants with normal weight. Thus, transitory presence of MDSC after birth is critical for the maintenance of immune homeostasis.