A5014331402- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Biochemical Acid Research Studies
- Circadian rhythm and melatonin
- Genomics, phytochemicals, and oxidative stress
- Redox biology and oxidative stress
- Cellular transport and secretion
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Coenzyme Q10 studies and effects
- Birth, Development, and Health
- interferon and immune responses
- Biochemical effects in animals
- Phagocytosis and Immune Regulation
- Photosynthetic Processes and Mechanisms
- Spaceflight effects on biology
- GDF15 and Related Biomarkers
- RNA modifications and cancer
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
University of Massachusetts Chan Medical School
2016-2025
University of Massachusetts Amherst
2024
Memorial Sloan Kettering Cancer Center
2010-2018
Cornell University
2011-2017
Kettering University
2011
New York University
2006-2010
University of Missouri–Kansas City
2002-2006
Whitehead Institute for Biomedical Research
2006
University of Pennsylvania
2006
Howard Hughes Medical Institute
2006
Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation cytotoxic, but little known about its normal function or pathobiology. The earliest defect following expression was a block endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, Rab guanosine...
To better understand the response to mitochondrial dysfunction, we examined mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses stress and communicates nucleus during unfolded protein (UPR(mt)) in Caenorhabditis elegans. We found that key point of regulation is import efficiency ATFS-1. In addition a nuclear localization sequence, has an N-terminal targeting sequence essential for UPR(mt) repression. Normally, imported into mitochondria degraded....
Deterioration of adult stem cells accounts for much aging-associated compromised tissue maintenance. How maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch the mitochondrial unfolded protein response (UPR(mt)), which is mediated by interplay SIRT7 and NRF1 coupled to cellular energy metabolism proliferation. inactivation caused reduced quiescence, increased folding stress (PFS(mt)), regenerative capacity hematopoietic (HSCs). expression was in aged HSCs,...
Perturbation of the protein-folding environment in mitochondrial matrix selectively upregulates expression nuclear genes encoding chaperones. To identify components signal transduction pathway(s) mediating this unfolded protein response (UPR(mt)), we first isolated a temperature-sensitive mutation (zc32) that conditionally activates UPR(mt) C. elegans and subsequently searched for suppressors by systematic inactivation genes. RNAi ubl-5, gene ubiquitin-like protein, suppresses activation...
Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway regulates of chaperone genes during dysfunction. Here, we report GCN-2, an eIF2α kinase modulates cytosolic protein synthesis, functions a complementary ATFS-1. During dysfunction, GCN-2–dependent phosphorylation is required for development as well lifespan extension observed...
Abstract Inhibition of the master growth regulator mTORC1 (mechanistic target rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress synthesis through integrated stress response (ISR), resulting preferential translation transcription factor ATF-4. Here we show C. elegans that inhibition or increases ATF-4 expression, and mediates longevity under these conditions independently ISR signalling. promotes activating canonical...
Severe forms of malaria are associated with systemic inflammation and host metabolism disorders; however, the interplay between these outcomes is poorly understood. Using a Plasmodium chabaudi model malaria, we demonstrate that interferon (IFN) γ boosts glycolysis in splenic monocyte-derived dendritic cells (MODCs), leading to itaconate accumulation disruption TCA cycle. Increased levels reduce mitochondrial functionality, which associates organellar nucleic acid release MODC restraint. We...
In Caenorhabditis elegans, the programmed repression of heat shock response (HSR) accompanies transition to reproductive maturity, leaving cells vulnerable environmental stress and protein aggregation with age. To identify factors driving this event, we performed an unbiased genetic screen for suppressors resistance identified mitochondrial electron transport chain (ETC) as a central regulator age-related decline HSR cytosolic proteostasis. Mild downregulation ETC activity, either by...