A5026688221- Autophagy in Disease and Therapy
- Helicobacter pylori-related gastroenterology studies
- NF-κB Signaling Pathways
- RNA regulation and disease
- Immune Response and Inflammation
- Digestive system and related health
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Gastrointestinal motility and disorders
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- interferon and immune responses
- Cancer Cells and Metastasis
- Bacteriophages and microbial interactions
- Trace Elements in Health
- Genetic factors in colorectal cancer
- Clostridium difficile and Clostridium perfringens research
- IL-33, ST2, and ILC Pathways
The University of Texas Southwestern Medical Center
2013-2022
Southwestern Medical Center
2013-2022
Mayo Clinic
2014
Institute of Molecular Biology and Genetics
2005-2010
National Academy of Sciences of Ukraine
2005-2007
COMMD1 deficiency results in defective copper homeostasis, but the mechanism for this has remained elusive. Here we report that is directly linked to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62. This COMMD/CCDC22/CCDC93 (CCC) interacts multisubunit WASH complex, an evolutionarily conserved system, which required endosomal deposition of F-actin cargo trafficking conjunction retromer. Interactions between subunit FAM21,...
The question whether or not "viruses are alive" has caused considerable debate over many years. Yet, the is effectively without substance because answer depends entirely on definition of life state "being that bound to be arbitrary. In contrast, status viruses among biological entities readily defined within replicator paradigm. All replicators form a continuum along selfishness-cooperativity axis, from completely selfish fully cooperative forms. Within this range, typical, lytic represent...
NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis immune disorders cancer. Its regulation involves variety steps, including controlled degradation inhibitory IκB proteins. In addition, inactivation DNA-bound essential for its regulation. This step requires factor known as copper metabolism Murr1 domain–containing 1 (COMMD1), prototype member conserved gene family. While COMMD proteins have linked to ubiquitination pathway, little else about other family...
Chronic inflammation and gut microbiota dysbiosis, in particular the bloom of genotoxin-producing E. coli strains, are risk factors for development colorectal cancer. Here, we sought to determine whether precision editing metabolism composition could decrease tumor mouse models colitis-associated cancer (CAC). Expansion experimentally introduced strains azoxymethane/dextran sulfate sodium colitis model was driven by molybdoenzyme-dependent metabolic pathways. Oral administration tungstate...
Cullin RING ligases (CRLs), the most prolific class of ubiquitin ligase enzymes, are multimeric complexes that regulate a wide range cellular processes. CRL activity is regulated by CAND1 (Cullin-associated Nedd8-dissociated protein 1), an inhibitor promotes dissociation substrate receptor components from CRL. We demonstrate here COMMD1 (copper metabolism MURR1 domain-containing factor previously found to promote ubiquitination various substrates, regulates activation antagonizing binding....
Inflammatory bowel disease (IBD) affects 1.5–3.0 million people in the United States. IBD is genetically determined and many common risk alleles have been identified. Yet, a large proportion of genetic predisposition remains unexplained. In this study, we report identification an ultra rare missense variant (NM_006998.3:c.230G > A;p.Arg77His) SCGN gene causing Mendelian early-onset ulcerative colitis. encodes calcium sensor that exclusively expressed neuroendocrine lineages, including...
X-linked reticulate pigmentary disorder (XLPDR, Mendelian Inheritance in Man #301220) is a rare syndrome characterized by recurrent infections and sterile multiorgan inflammation. The caused an intronic mutation POLA1, the gene encoding catalytic subunit of DNA polymerase-α (Pol-α), which responsible for Okazaki fragment synthesis during replication. Reduced POLA1 expression this condition triggers spontaneous type I interferon expression, can be linked to autoinflammatory manifestations...
Autophagy is a process in which eukaryotic (but not prokaryotic) cell destroys its own components through the lysosomal machinery. This tightly regulated essential for normal growth, development, and homeostasis, serving to maintain balance between synthesis degradation, resulting recycling of cellular products. Here we try expand concept autophagy define it as general mechanism regulation encompassing various levels biosphere. Interestingly, one consequences such an approach that must...
Physiologic microbe-host interactions in the intestine require maintenance of microbiota a luminal compartment through complex interplay between epithelial and immune cells. However, roles mucosal myeloid cells this process remain incompletely understood. In study, we identified that decreased cell phagocytic activity promotes colon tumorigenesis. We show is due to bacterial accumulation lamina propria present evidence underlying mechanism induction prostaglandin production by Moreover,...
Paneth cells (PCs) are small intestinal epithelial that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived secretion is relevant vivo remains unknown ablation of does not affect homeostatic proliferation or restitution after irradiation injury. Considering importance factors tumor development, we explored here role PCs carcinogenesis using a genetic model PC depletion through conditional expression diphtheria toxin-α subunit....
<h3>Background:</h3> Autologous anti-CD19 CAR T cells are showing early clinical evidence of safety and efficacy for the treatment numerous autoimmune diseases[1]. Allogeneic have potential to further address drug supply substantial B-cell driven disease population with advantages that include scalability, removal need patient apheresis, reduced wait times[2]. Emerging data in trials suggests long-term cell persistence is not required as patients achieved remissions (> 1 year) despite...
Abstract Dysregulated IL-17 expression is central to the pathogenesis of several inflammatory disorders, including ulcerative colitis. We have shown earlier that SUMOylation ROR-γt, transcription factor for IL-17, regulates colonic inflammation. In this study, we show Ubc9, E2 enzyme targets ROR-γt SUMOylation, significantly reduced in mucosa colitis patients. Mechanistically, demonstrate hypoxia-inducible 1α (HIF-1α) binds a CpG island within Ubc9 gene promoter, resulting its...
Our body harbors hundreds of microbial species and contains many more bacterial than human cells. These microbes are not passive riders but rather a vital component the organism. The microbiota affects our health in multiple ways, both positively negatively. One new attractive directions microbiome biology is “microbiome-brain axis”. Several groups researchers have described ability gut to communicate with brain thus modulate behavior. limited experimental data became foundation “biomeme...
Abstract The genetic basis of inflammatory bowel disease remains to be elucidated completely. Here we report on a patient with who has mosaic tetrasomy the short arm chromosome 9, genomic region that harbours type I interferon gene cluster. We show increased activation is present in peripheral blood and intestinal tissue from this patient, similar previous reports autoinflammatory organ damage driven by other patients chromosomal abnormality. To our knowledge, first case 9p-associated...