A5019785447- Genomics and Chromatin Dynamics
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Retinoids in leukemia and cellular processes
- Galectins and Cancer Biology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- GDF15 and Related Biomarkers
- Muscle Physiology and Disorders
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Nutrition and Health in Aging
- Pancreatic function and diabetes
- Nuclear Receptors and Signaling
- Fungal and yeast genetics research
- Antimicrobial Peptides and Activities
- Bacterial Genetics and Biotechnology
- Bariatric Surgery and Outcomes
- Diet and metabolism studies
- Diabetes Treatment and Management
- Ubiquitin and proteasome pathways
NGM Biopharmaceuticals (United States)
2012-2022
University of Virginia Health System
2005-2012
University of California, San Diego
2006-2010
University of Virginia
2003
Hepatocellular carcinoma (HCC), one of the leading causes cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, also implicated development HCC. In humans, amplified HCC and its expression induced liver under cholestatic cirrhotic conditions. mice, ectopic overexpression drives a process requires FGFR4. this study, we describe an...
The RNA polymerase II core promoter is a critical yet often overlooked component in the transcription process. defined as stretch of DNA, which encompasses start site and typically approx. 40–50 nt length, that directs initiation gene transcription. In past, it has been generally presumed promoters are general function occurs via common shared mechanism. Recent studies have revealed, however, there considerable diversity structure function. There number DNA elements contribute to activity,...
The TCT motif (polypyrimidine initiator) encompasses the transcription start site of nearly all ribosomal protein genes in Drosophila and mammals. is required for gene promoters. element resembles Inr (initiator), but not recognized by TFIID cannot function lieu an Inr. However, a single T-to-A substitution converts into functionally active Thus, novel transcriptional that distinct from These findings reveal specialized TCT-based system directed toward synthesis proteins.
The regulation of gene transcription is critical for the proper development and growth an organism. protein-coding genes initiates at RNA polymerase II core promoter, which a diverse module that can be controlled by many different elements such as TATA box downstream promoter element (DPE). To understand basis diversity, we explored potential biological functions DPE. We found nearly all Drosophila homeotic (Hox) promoters, lack TATA-box elements, contain functionally important DPE motifs...
Abstract Suppressive myeloid cells inhibit antitumor immunity by preventing T-cell responses. Immunoglobulin-like transcript 3 (ILT3; also known as LILRB4) is highly expressed on tumor-associated and promotes their suppressive phenotype. However, the ligand that engages ILT3 within tumor microenvironment renders unknown. Using a screening approach, we identified fibronectin functional for ILT3. The interaction of with polarized toward state, these effects were reversed an ILT3-specific...
The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional module. RNAi depletion overexpression experiments revealed genetic circuit that controls the balance of transcription from two motifs, TATA box downstream element (DPE). In this circuit, TBP activates TATA-dependent represses DPE-dependent transcription, whereas Mot1 NC2 block function thus repress activate transcription. This regulatory likely to be one means by which biological networks can...
Gastrointestinal bypass surgeries that result in rerouting and subsequent exclusion of nutrients from the duodenum appear to rapidly alleviate hyperglycemia hyperinsulinemia independent weight loss. While mechanism(s) responsible for normalization glucose homeostasis remains be fully elucidated, this rapid coupled with well-known effects vagal inputs into suggests a neurohormonally mediated mechanism. Our results show duodenal surgery on obese, insulin-resistant Zucker fa/fa rats restored...
Mot1 is an essential Snf2/Swi2-relatedSaccharomyces cerevisiae protein that binds the TATA-binding (TBP) and removes TBP from DNA using ATP hydrolysis. functions in vivo both as a repressor activator of transcription. catalysis TBP·DNA disruption consistent with its function repressor, but mechanism activation unknown. To better understand physiologic role enzymatic mechanism, MOT1mutants were generated tested for activity vitro vivo. The results demonstrate close correlation between...
A large body of literature provides compelling evidence for the role evolutionarily conserved core histone residues in various biological processes. However, site-directed mutagenesis individual that are known to be sites posttranslational modifications often does not result clear phenotypic defects. In some cases, combination multiple mutations can give rise stronger phenotypes, implying functional redundancy between distinct on histones. Here, we examined “histone hypothesis” by...
<div>Abstract<p>Hepatocellular carcinoma (HCC), one of the leading causes cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, also implicated development HCC. In humans, amplified HCC and its expression induced liver under cholestatic cirrhotic conditions. mice, ectopic overexpression drives a process requires FGFR4....
<div>Abstract<p>Hepatocellular carcinoma (HCC), one of the leading causes cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, also implicated development HCC. In humans, amplified HCC and its expression induced liver under cholestatic cirrhotic conditions. mice, ectopic overexpression drives a process requires FGFR4....
<div>Abstract<p>Suppressive myeloid cells inhibit antitumor immunity by preventing T-cell responses. Immunoglobulin-like transcript 3 (ILT3; also known as LILRB4) is highly expressed on tumor-associated and promotes their suppressive phenotype. However, the ligand that engages ILT3 within tumor microenvironment renders unknown. Using a screening approach, we identified fibronectin functional for ILT3. The interaction of with polarized toward state, these effects were reversed an...
<div>Abstract<p>Suppressive myeloid cells inhibit antitumor immunity by preventing T-cell responses. Immunoglobulin-like transcript 3 (ILT3; also known as LILRB4) is highly expressed on tumor-associated and promotes their suppressive phenotype. However, the ligand that engages ILT3 within tumor microenvironment renders unknown. Using a screening approach, we identified fibronectin functional for ILT3. The interaction of with polarized toward state, these effects were reversed an...
Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells
Supplementary Figure from The Fibronectin–ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells
<h3>Background</h3> Targeting the immunosuppressive tumor microenvironment to enhance or recover anti-tumor functions is a promising strategy favor regression and response checkpoint immunotherapy. LILRB4 an inhibitory immune receptor, also named ILT3, that primarily expressed in myeloid cells. We previously showed with <i>in vitro</i> assays ILT3 highly tumor-associated macrophages (TAMs) binds fibronectin (Fn), which ubiquitously extracellular matrix enriched various primary tissues...