A5071401290- Advanced Glycation End Products research
- Muscle Physiology and Disorders
- CAR-T cell therapy research
- Virus-based gene therapy research
- Tissue Engineering and Regenerative Medicine
- Diabetes and associated disorders
- Mechanisms of cancer metastasis
- Pluripotent Stem Cells Research
- Structural Behavior of Reinforced Concrete
- RNA Interference and Gene Delivery
- Bladder and Urothelial Cancer Treatments
- Infrastructure Maintenance and Monitoring
- Immune cells in cancer
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Chronic Kidney Disease and Diabetes
- Genetics, Aging, and Longevity in Model Organisms
- Glycosylation and Glycoproteins Research
- Telomeres, Telomerase, and Senescence
- Structural Integrity and Reliability Analysis
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- Exercise and Physiological Responses
Harvard University
2021-2025
Harvard Stem Cell Institute
2021-2025
Joslin Diabetes Center
2021
National Institute on Aging
2016-2018
Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly large, anatomically distributed tissues such as skeletal muscle. Here, we establish an strategy evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery desired tissues. Using this method, identify a class RGD motif-containing capsids...
Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform into rapidly dividing (activated) stem/progenitor mediate muscle repair after injury remain largely unknown. Here we identify prominent FBJ osteosarcoma oncogene (Fos) mRNA and protein signature recently activated is rapidly, heterogeneously, transiently induced by damage. We further...
The generation of myotubes from fibroblasts upon forced MyoD expression is a classic example transcription factor-induced reprogramming. We recently discovered that additional modulation signaling pathways with small molecules facilitates reprogramming to more primitive induced myogenic progenitor cells (iMPCs). Here, we dissected the transcriptional and epigenetic dynamics mouse undergoing either or iMPCs using MyoD-inducible transgenic model. Induction in combined generated Pax7 + high...
The Receptor for Advanced Glycation End Products (RAGE), classically considered a mediator of acute and chronic inflammatory responses, has recently been implicated by genetic knockout studies as regulator skeletal muscle physiology during development following injury. Yet, the role its soluble isoform, RAGE (sRAGE), in regeneration remains relatively unexplored. To address this knowledge gap, Adeno-Associated Virus (AAV) mediated knockin supplementation strategies were developed to...
The receptor for advanced glycation end products (RAGE) interacts with multiple ligands and transmits inflammatory signals from damage- pathogen-associated molecular patterns (DAMPs PAMPs) to cellular programs. RAGE shares another group of PRRs, i.e., Toll-like receptors. Such ligand-receptor promiscuity generates coordinated complex signaling that provide a basis the development inflammaging diseases. Soluble (sRAGE) functions as decoy scavenges DAMP/PAMP dampens signals. Epidemiological...
The receptor for advanced glycation end products (RAGE) is a multi-ligand, immunoglobulin-like that has been implicated in aging-associated diseases. Recent studies have demonstrated both human and murine Ager genes undergo extensive alternative splicing generates multiple putative transcripts encoding different isoforms. Except the soluble isoform (esRAGE), majority of RAGE isoforms remain unstudied. Profiling showed variant transcript 4 (mRAGE_v4), second most abundant lungs other tissues,...
Abstract Aging is a complex process that manifests through the time-dependent functional decline of biological system. Age-related changes in epigenetic and transcriptomic profiles have been successfully used to measure aging 1,2 . Moreover, modulating gene regulatory networks interventions such as induction Yamanaka factors has shown reverse signatures improve cell function 3,4 However, this intervention safety efficacy limitations for vivo rejuvenation 5,6 , underscoring need identifying...