A5027124787- Heat shock proteins research
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- Mitochondrial Function and Pathology
- Fibromyalgia and Chronic Fatigue Syndrome Research
- RNA Interference and Gene Delivery
- Cardiomyopathy and Myosin Studies
- Exercise and Physiological Responses
- Advanced biosensing and bioanalysis techniques
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Fungal and yeast genetics research
- Bacteriophages and microbial interactions
- Genetics, Aging, and Longevity in Model Organisms
- Alzheimer's disease research and treatments
- Carcinogens and Genotoxicity Assessment
- Parkinson's Disease Mechanisms and Treatments
- Cardiovascular Effects of Exercise
- Trace Elements in Health
- Biosensors and Analytical Detection
- Nuclear Structure and Function
Washington University in St. Louis
2020-2024
National Institute of Pharmaceutical Education and Research
2012-2016
Small molecules with antioxidative properties have been implicated in amyloid disorders. Curcumin is the active ingredient present turmeric and known for several biological medicinal effects. Adequate evidence substantiates importance of curcumin Alzheimer's disease recent suggests its role Prion Parkinson's disease. However, contradictory effects suggested Huntington's This difference provided a compelling reason to investigate effect on glutamine-rich (Q-rich) non-glutamine-rich (non...
Dominant mutations in the HSP70 cochaperone DNAJB6 cause a late-onset muscle disease termed limb-girdle muscular dystrophy type D1 (LGMDD1), which is characterized by protein aggregation and vacuolar myopathology. Disease reside within G/F domain of DNAJB6, but molecular mechanisms underlying dysfunction are not well understood. Using yeast, cell culture, mouse models LGMDD1, we found that toxicity associated with disease-associated required its interaction abrogating this genetically or...
Conflicting reports exist in the literature regarding role of wild-type huntingtin determining toxicity aggregated, mutant Huntington's disease (HD). Some studies report amelioration protein presence protein, while others indicate sequestration by huntingtin. Over years, yeast has been established as a valid model organism to study molecular changes associated with HD, especially at level. We have used an inducible system express human fragments harboring normal (25Q) and pathogenic (103Q)...
Maintenance of cellular redox homoeostasis forms an important part the defence mechanism and continued cell viability. Despite extensive studies, role chaperone Hsp104 (heat-shock protein 102 kDa) in propagation misfolded aggregates generation oxidative stress remains poorly understood. Expression RNQ1-RFP Saccharomyces cerevisiae cells led to prion form increased stress. In present study, we show that disruption isogenic yeast strain solubilization RNQ1-RFP. This reduced generated cell. The...
Abstract Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays vital role cellular proteostasis. Recessive loss-of-function cause myopathy with early respiratory failure spinal rigidity, presenting infancy adulthood. This study investigated broader clinical genetic spectrum of myopathy. In this study, we performed whole-exome sequencing on seven patients...
Abstract Chronic stress and prolonged activation of defence pathways have deleterious consequences for the cell. Dietary restriction is believed to be beneficial as it induces cellular response machinery. We report here that although phenomenon in a wild-type cell, dietary leads an inconsistent cell already under proteotoxicity-induced stress. Using yeast model Huntington’s disease, we show contrary expectation, aggregation mutant huntingtin exacerbated unfolded protein pathway dampened...
Formation of cytoplasmic and nuclear aggregates is a hallmark Huntington's disease (HD). Inhibition aggregation mutant huntingtin has been suggested to be feasible approach slow down the progress this neurodegenerative disorder. Exposure environmental stimuli leads activation stress response machinery cell. In work, we have investigated effect salt shock on (103Q-htt) in yeast model HD. We found that at an optimum concentration NaCl, protein no longer formed existed soluble form. This led...
Abstract Dominant mutations in the HSP70 co-chaperone DNAJB6 cause a late onset muscle disease termed limb girdle muscular dystrophy type 1D (LGMD1D), which is characterized by protein aggregation and vacuolar myopathology. Disease reside within G/F domain of DNAJB6, but molecular mechanisms underlying dysfunction are not well understood. Using yeast, cell culture, mouse models LGMD1D, we find that toxicity associated with disease-associated requires its interaction HSP70, abrogating this...
Abstract Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations deficiencies within chaperone network can lead to disease. Dominant DNAJB6 (Hsp40)—an Hsp70 co-chaperone—lead a protein aggregation-linked myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). Here, we used yeast prion model client in conjunction with vitro activity assays gain mechanistic insights into molecular basis LGMDD1. show how...
Abstract The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone that binds near the ribosome exit tunnel and first point of contact for newly synthesized proteins. Deletion NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown deletion rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize disruption would improve viability expressing human misfolding Here, we show improves expanded...
The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone that binds near the ribosome exit tunnel and first point of contact for newly synthesized proteins. Deletion NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown deletion rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize disruption would improve viability expressing human misfolding Here, we show improves expanded polyglutamine also...
<title>Abstract</title> Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays vital role cellular proteostasis. Recessive loss-of-function <italic>DNAJB4</italic> cause myopathy with early respiratory failure spinal rigidity, presenting infancy adulthood. This study investigated broader clinical genetic spectrum of myopathy. In this study, we performed...
Abstract Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations deficiencies within chaperone network can lead to disease. In fact, dominant in DNAJB6 (Hsp40/Sis1), an Hsp70 co-chaperone, leads a protein aggregate myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). client co-chaperone interactions skeletal muscle are not known. Here, we used yeast prion model conjunction with vitro activity assays...
Abstract DNAJ/HSP40 co-chaperones are integral to the chaperone network, bind client proteins and recruit them HSP70 for folding. We performed exome sequencing on patients with a presumed hereditary muscle disease no genetic diagnosis. This identified four individuals from three unrelated families carrying an unreported homozygous stop gain (c.856A>T; p.Lys286Ter), or missense variants (c.74G>A; p.Arg25Gln c.785T>C; p.Leu262Ser) in DNAJB4. Affected presented axial rigidity early...
Abstract Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations deficiencies within chaperone network can lead to disease. In fact, dominant in DNAJB6 (Hsp40/Sis1), an Hsp70 co-chaperone, leads a protein aggregate myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). client co-chaperone interactions skeletal muscle are not known. Here, we used yeast prion model conjunction with vitro activity assays...