A5062052747- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Exercise and Physiological Responses
- Adipose Tissue and Metabolism
- Neurogenetic and Muscular Disorders Research
- Chronic Lymphocytic Leukemia Research
- Invertebrate Immune Response Mechanisms
- Animal Genetics and Reproduction
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Peroxisome Proliferator-Activated Receptors
- Mesenchymal stem cell research
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Nutrition and Health in Aging
- Erythrocyte Function and Pathophysiology
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Extracellular vesicles in disease
- Cellular transport and secretion
St. Jude Children's Research Hospital
2022-2025
University of America
2018
Catholic University of America
2018
Abstract Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to repair but whether platelets promote beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines early event necessary for mice. Platelet depletion reduces the levels platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase...
Abstract Ubiquitination is a post-translational modification initiated by the E1 enzyme UBA1, which transfers ubiquitin to ~35 E2 ubiquitin-conjugating enzymes. While UBA1 loss cell lethal, it remains unknown how partial reduction in activity endured. Here, we utilize deep-coverage mass spectrometry define E1-E2 interactome and determine proteins that are modulated knockdown of each human cells. These analyses UBA1/E2-sensitive proteome specificity protein modulation. Interestingly, profound...
Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which maintain proteostasis during aging. Here, we find that have diverse roles in handling a model aggregation-prone (huntingtin-polyQ) Drosophila retina: while some mediate aggregate assembly, UBE2D/effete (eff) other required huntingtin-polyQ degradation. UBE2D/eff is skeletal muscle: eff levels decline...
Abstract Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy the diaphragm, major responsible for breathing, an important determinant cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators myofiber growth. Subsequent testing mouse myotubes revealed Fibcd1...
Abstract Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored platelet α‐granules dense granules are released activation clotting. Emerging evidence indicates that such platelet‐derived signaling factors instrumental guiding regeneration. Here, we discuss the roles of platelet‐secreted skeletal muscle Chemokines secreted by platelets early phase after injury needed to recruit neutrophils injured...
MotivationEukaryotic cells have evolved complex functions via their compartmentalization into organelles and subcellular microenvironments. Such specialization of the cellular space enabled optimal function but also resulted in compartment-specific challenges to proteostasis. However, due paucity tools, how proteostasis is regulated physiological pathological conditions remains largely uncharted. In this study, we generated Drosophila strains that ubiquitously express misfolding-prone FlucDM...
Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues largely unknown. Here, we find the heart skeletal muscle undergo at early stages are transcriptionally most impacted by cachexia. We also identify general organ-specific transcriptional changes indicate functional derangement even in do not wasting, such as brain. Secreted factors constitute top category of cancer-regulated genes host...
Ubiquitin-conjugating enzymes (E2s) are key for regulating protein function and turnover via ubiquitination but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that have diverse roles in handling a model aggregation-prone (huntingtin-polyQ) the Drosophila retina: while some mediate aggregate assembly, UBE2D/effete (eff) other required huntingtin-polyQ degradation. UBE2D/eff is also skeletal muscle: eff levels decline with aging, muscle-specific knockdown...
A major focus for our laboratory is identifying the molecules and mechanisms that regulate basolateral-to-apical transcytosis in polarized hepatocytes. Our most recent studies have focused on characterizing biochemical functional properties of small rab17 GTPase. We determined a monosumoylated protein this modification likely mediates selective interactions with apically located syntaxin 2. Using hepatic WIF-B cells exogenously expressing wild-type, dominant active/guanosine triphosphate...
Ubiquitin-conjugating enzymes (E2s) are key for regulating protein function and turnover via ubiquitination but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that have diverse roles in handling a model aggregation-prone (huntingtin-polyQ) the
Ubiquitin-conjugating enzymes (E2s) are key for regulating protein function and turnover via ubiquitination but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that have diverse roles in handling a model aggregation-prone (huntingtin-polyQ) the Drosophila retina: while some mediate aggregate assembly, UBE2D/effete (eff) other required huntingtin-polyQ degradation. UBE2D/eff is also skeletal muscle: eff levels decline with aging, muscle-specific knockdown...
Ubiquitin controls many cellular processes via its post-translational conjugation onto substrates. Its use is highly variable due to ability form poly-ubiquitin with various topologies. Among them, linear chains have emerged as important regulators of immune responses and protein degradation. Previous studies in
Abstract Ubiquitin controls many cellular processes via its posttranslational conjugation onto substrates. Its use is highly variable due to ability form poly-ubiquitin chains with various topologies. Among them, linear have emerged as important regulators of immune responses and protein degradation. Previous studies in Drosophila melanogaster found that expression cannot be dismantled into single moieties leads their ubiquitination degradation or, alternatively, proteins. However, it...
Ubiquitin-conjugating enzymes (E2s) are key for regulating protein function and turnover via ubiquitination but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that have diverse roles in handling a model aggregation-prone (huntingtin-polyQ) the Drosophila retina: while some mediate aggregate assembly, UBE2D/effete (eff) other required huntingtin-polyQ degradation. UBE2D/eff is also skeletal muscle: eff levels decline with aging, muscle-specific knockdown...
Aging and wasting of skeletal muscle reduce organismal fitness. Regrettably, only limited interventions are currently available to address this unmet medical need. Many methods have been developed study condition, including the intramuscular electroporation DNA plasmids. However, technique requires surgery high electrical fields, which cause tissue damage. Here, we report an optimized protocol for small interfering RNAs (siRNAs) into tibialis anterior mice. This does not require and, because...