A5054416615- Genetics, Aging, and Longevity in Model Organisms
- Pain Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Alcohol Consumption and Health Effects
- Muscle metabolism and nutrition
- Cholesterol and Lipid Metabolism
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Single-cell and spatial transcriptomics
- Telomeres, Telomerase, and Senescence
- Diabetic Foot Ulcer Assessment and Management
- Diabetes Treatment and Management
- Peripheral Neuropathies and Disorders
- Neurological Disorders and Treatments
- Molecular Biology Techniques and Applications
- Clinical practice guidelines implementation
- Medical Coding and Health Information
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Nuclear Structure and Function
- Alzheimer's disease research and treatments
Boston Children's Hospital
2022-2025
Buck Institute for Research on Aging
2017-2022
Harvard University
2022
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain
The risk of cardiovascular disease in type 1 diabetes remains extremely high, despite marked advances blood glucose control and even the widespread use cholesterol synthesis inhibitors. Thus, a deeper understanding insulin regulation metabolism, its disruption diabetes, could reveal better treatment strategies.To define mechanisms by which controls plasma levels, we knocked down receptor, FoxO1, key bile acid enzyme, CYP8B1. We measured composition, absorption, cholesterol. In parallel,...
Abstract Dysregulation of mTOR complex 1 (mTORC1) activity drives neuromuscular junction (NMJ) structural instability during aging; however, downstream targets mediating this effect have not been elucidated. Here, we investigate the roles two mTORC1 phosphorylation for mRNA translation, ribosome protein S6 kinase (S6K1) and eukaryotic translation initiation factor 4E-binding (4EBP1), in regulating NMJ induced by aging sustained activation. While myofiber-specific deletion S6k1 has no on...
Abstract Background Chronic mTORC1 activation in skeletal muscle is linked with age‐associated loss of mass and strength, known as sarcopenia. Genetic by conditionally ablating upstream inhibitor TSC1 accelerates sarcopenia development adult mice. Conversely, genetic suppression downstream effectors protein synthesis delays natural aging promotes activating ribosomal S6 kinases (S6Ks) inhibiting eIF4E‐binding proteins (4EBPs). Whole‐body knockout S6K1 or muscle‐specific over‐expression a...
Abstract Aging is the major risk factor for development of dementia and neurodegenerative disorders, aging brain manifests severe deficits in buffering capacity by proteostasis network. Accordingly, we investigated significance unfolded protein response (UPR), a signaling pathway that copes with endoplasmic reticulum (ER) stress, to normal mammalian aging. Genetic disruption ER stress sensor IRE1α accelerated cognitive motor dysfunction during Exogenous bolstering UPR overexpressing an...
Abstract The mechanistic target of rapamycin (mTOR) signaling pathway plays a central role in aging and number different disease states. Rapamycin, which suppresses activity the mTOR complex 1 (mTORC1), shows preclinical (and sometimes clinical) efficacy models. Among these are Lmna −/− mice, serve as mouse model for dystrophy-associated laminopathies. To confirm that elevated mTORC1 is responsible pathology manifested mice to decipher downstream genetic mechanisms underlying benefits...
Abstract Background Digital multiplex gene expression profiling is overcoming the limitations of many tissue-processing and RNA extraction techniques for reproducible quantitative molecular classification disease. We assessed effect different skin biopsy collection/storage conditions on mRNA quality quantity NanoString nCounter™ System’s ability to reproducibly quantify 730 immune genes from biopsies. Methods Healthy human punch biopsies ( n = 6) obtained sections four patients undergoing...
Alcohol is one of the most widely encountered drugs in world and credited with a wealth health interactions. Light to moderate regular consumption (14–28 g daily) can promote heart health, protect against Type II diabetes, likely extend overall lifespan. However, higher rates lead detrimental effects more associated ethanol consumption, including decreased motor control, cardiotoxicity, insulin resistance, liver disease. Despite high elderly population, there has been little focus on...
Abstract Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset progression DPN have been linked with dyslipidemia hyperglycemia3, contribution inflammation in pathogenesis has not investigated. Here, we use High Fat Fructose Diet (HFHFD) to model its metabolic syndrome mice. mice develop persistent heat hypoalgesia after three months, but reduction epidermal skin innervation only manifests at 6...
Diabetes Care for You (DCFY) is a multi-professional specialist community service adults living with Type 1 and 2 diabetes in Brighton, Hove/High Weald, Lewes Havens CCGs. There are 1195 people 3390 currently. The DCFY team were unable to access real-time population level data, user friendly way. Meaning an increasing proportion of time was dedicated generating information. This inability meant that targets, such as referral treatment waiting times (RTT) could not be predicted. A bespoke...
Abstract Brain ageing is the main risk factor to develop dementia and neurodegenerative diseases, associated with a decay in buffering capacity of proteostasis network. We investigated significance unfolded protein response (UPR), major signaling pathway cope ER stress, functional deterioration brain during aging. Genetic disruption stress sensor IRE1α accelerated cognitive motor decline ageing. Exogenous bolstering UPR by overexpressing an active form transcription XBP1 restored synaptic...