A5061113163- Genetics, Aging, and Longevity in Model Organisms
- Microbial Metabolic Engineering and Bioproduction
- Diet and metabolism studies
- Birth, Development, and Health
- Biochemical Acid Research Studies
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Selenium in Biological Systems
- Folate and B Vitamins Research
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Coenzyme Q10 studies and effects
- DNA Repair Mechanisms
- Protein Structure and Dynamics
- Evolution and Genetic Dynamics
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
University of Massachusetts Chan Medical School
2015-2025
Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and propionate shunt is used when B12 levels are low. The kept off there sufficient flux through canonical pathway, likely avoid generating shunt-specific toxic intermediates. Here, we discovered transcriptional regulatory circuit activates gene...
Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of results accumulation transcriptional activation a shunt pathway. This propionate-dependent mechanism requires nhr-10 referred to as ‘B12-mechanism-I’. Here, we report represses expression Met/SAM cycle genes by propionate-independent refer...
Abstract In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology response therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect state of Massachusetts, USA, flatten curve spread novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers state, this meant putting hold on experiments for nine weeks until May 18, 2020. To keep lab engaged productive, enhance communication...
Abstract In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology, response therapeutic drugs. Visualization of metabolic pathways that comprise network is extremely useful for interpreting a wide variety experiments. Detailed annotated pathway maps C. are mostly limited pan-organismal maps, many incomplete or inaccurate enzyme annotations. Here, present WormPaths, which composed two parts: (1) careful manual...
In humans, mutations in D-2-hydroxyglutarate (D-2HG) dehydrogenase (D2HGDH) result D-2HG accumulation, delayed development, seizures, and ataxia. While the mechanisms of 2HG-associated diseases have been studied extensively, endogenous metabolism remains unclear any organism. Here, we find that, Caenorhabditis elegans, is produced propionate shunt, which transcriptionally activated when flux through canonical, vitamin B12-dependent breakdown pathway perturbed. Loss D2HGDH ortholog, dhgd-1,...
Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and methylmalonyl-CoA mutase catabolize short-chain fatty acid propionate. In nematode Caenorhabditis elegans, maternally supplied vitamin is required development of offspring. However, mechanism exporting from mother offspring not yet known. Here, we use RNAi more than 200 transporters with B12-sensor transgene identify ABC transporter MRP-5 candidate exporter. We show...
Metabolic perturbations can affect gene expression, for instance to rewire metabolism. While numerous efforts have measured expression in response individual metabolic perturbations, methods that determine all the a given or set of genes not been available. Here, we use gene-centered approach derive first-pass regulatory network Caenorhabditis elegans by performing RNAi more than 1,400 with 19 promoter reporter strains express fluorescent protein animal's intestine. We find generally...
Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans , low vitamin B12, or genetic perturbation of results accumulation transcriptional activation a shunt pathway. This propionate-dependent mechanism requires nhr-10 referred to as “B12-mechanism-I”. Here, we report represses expression Met/SAM cycle genes by propionate-independent refer...
SUMMARY In humans, mutations in D-2-hydroxyglutarate (D-2HG) dehydrogenase (D2HGDH) result D-2HG accumulation, delayed development, seizures, and ataxia. While the mechanisms of 2HG-associated diseases have been studied extensively, endogenous metabolism remains unclear any organism. Here, we find that, Caenorhabditis elegans , is produced propionate shunt, which transcriptionally activated when flux through canonical, vitamin B12-dependent breakdown pathway perturbed. Deletion D2HGDH...
SUMMARY Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and methylmalonyl-CoA mutase catabolize short chain fatty acid propionate. In nematode Caenorhabditis elegans , maternally supplied vitamin is required development of her offspring. However, mechanism exporting from mother offspring not yet known. Here, we use RNAi more than 200 transporters with B12-sensor transgene identify ABC transporter MRP-5 candidate...
ABSTRACT Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental signals. Gene regulatory network circuitries known as coherent type 1 feed-forward loops (FFLs) with AND-logic gates have been proposed function a persistence detector because it generates delay in target activation and prevents induction unless the input signal is sustained. While such circuit has found for L-arabinose utilization system E. coli , their existence relevance...