A5034500923- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- RNA Research and Splicing
- Vitamin D Research Studies
- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Atherosclerosis and Cardiovascular Diseases
- Genomics and Chromatin Dynamics
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Extracellular vesicles in disease
- Cardiovascular Disease and Adiposity
- Diet and metabolism studies
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Nerve injury and regeneration
- Endoplasmic Reticulum Stress and Disease
- Genetic Associations and Epidemiology
- Mitochondrial Function and Pathology
- Acute Myocardial Infarction Research
- Cardiac Fibrosis and Remodeling
Massachusetts Institute of Technology
2021-2024
Broad Institute
2021-2024
Northwestern University
2024
Karolinska Institutet
2014-2019
Exercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given challenge profiling heterogeneous effects across multiple tissues cell types. Here, we address this opposing exercise high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous visceral white adipose tissue skeletal muscle mice with interventions. We identify a prominent role mesenchymal stem cells (MSCs) exercise-induced adaptation....
Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the metabolism away neurotoxic (KYN) to production of kynurenic acid (KYNA). In present study, we investigated effect on in humans. KAT gene and protein was muscles endurance-trained subjects compared untrained subjects. Endurance caused increase plasma...
Abstract The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, enhances the expression of kynurenine aminotransferases (Kats), which convert into kynurenic acid. This reduces kynurenine-associated neurotoxicity generates glutamate as a byproduct. Here, we show that elevates aspartate levels increases glycolysis malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization transfer...
Cardiovascular disease plays a central role in the electrical and structural remodeling of right atrium, predisposing to arrhythmias, heart failure, sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) spatial transcriptomics gene expression changes human ex vivo atrial tissue pericardial fluid ischemic disease, myocardial infarction, non-ischemic failure using asymptomatic patients valvular who undergo preventive surgery as control group. We reveal substantial...
We examined whether skeletal muscle overexpression of PGC-1α1 or PGC-1α4 affected myokine secretion and neuromuscular junction (NMJ) formation. A microfluidic device was used to model endocrine signaling NMJ formation between primary mouse myoblast-derived myotubes embryonic stem cell-derived motor neurons. Differences in hydrostatic pressure allowed for fluidic isolation either cell type unidirectional the fluid phase. Myotubes were transduced overexpress PGC-1α4, quantified using a...
The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue expenditure through PGC-1α1 activation is potentially beneficial for systemic Pharmacological activators could be valuable tools the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because a transcriptional coactivator with no known ligand-binding properties. While, regulated by several mechanisms,...
Farnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known.We expressed each variant primary hepatocytes and evaluated global expression, profile, metabolic fluxes. Gene delivery variants to Fxr(-/-) mouse liver was performed evaluate their vivo. effects fasting physical exercise on Fxr splicing were determined.We show that splice isoforms...
Abstract Background Skeletal muscle mass and strength are crucial determinants of health. Muscle loss is associated with weakness, fatigue, insulin resistance. In fact, it predicted that controlling atrophy can reduce morbidity mortality diseases such as cancer cachexia sarcopenia. Methods We analyzed gene expression data from mice or human patients diverse pathologies identified LMCD1 a strongly skeletal function. transiently expressed silenced in mouse gastrocnemius primary cells...
Abstract Ischemic heart disease is globally the leading cause of death. It plays a central role in electrical and structural remodeling right atrium, predisposing to arrhythmias, failure, sudden Here, we provide first dissection gene expression changes live atrial tissue, using single-nuclei RNA-seq spatial transcriptomics. We investigate matched samples tissue pericardial fluid reveal substantial differences disease- associated all cell types, inflammatory microvascular dysfunction...
Abstract Our ultimate goal is to identify, characterize and therapeutically target the glioma cell population that responsible for treatment resistance recurrence following chemoradiation. Two types may have overlapping phenotypes are known influence radioresistance 1) quiescent cells 2) glioblastoma (GBM) stem (GSCs). The extent of overlap between these populations unknown as hypoxia immune on their radioresistant properties. We shown co-culturing with THP-1 macrophages dramatically...
Abstract Regular physical exercise has long been recognized to reverse the effects of diet-induced obesity, but molecular mechanisms mediating these multi-tissue beneficial remain uncharacterized. Here, we address this challenge by studying opposing training and high-fat diet at single-cell, deconvolution tissue-level resolutions across 3 metabolic tissues. We profile scRNA-seq in 204,883 cells, grouped into 53 distinct cell subtypes/states 22 major types, from subcuta-neous visceral white...
Abstract Intelligence is usually associated with the ability to perceive, retain and use information adapt changes in one’s environment. In this context, systems of living cells can be thought as intelligent entities. Here, we show that concepts non-equilibrium tuning compartmentalization are sufficient model manifestations cellular intelligence such specialization, division, fusion communication using language operads. We implement our framework an unsupervised learning algorithm, I nt C yt...
Abstract Metabolism plays a central role in evolution, as resource conservation is selective pressure for fitness and survival. Resource-driven adaptations offer good model to study evolutionary innovation more broadly. It remains unknown how resource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions. Here we show that tuning heterotypic condensates mediate resilience nutrient limitation. Network genomic integration phenotypic,...
Ischemic heart disease is globally the leading cause of death. It plays a central role in electrical and structural remodeling right atrium, predisposing to arrhythmias, failure, sudden Yet, mechanistic changes human atrium have not been investigated, although sinus node – natural pacemaker resides roof atrium. Here, we dissected gene expression live atrial tissue, using single-nuclei RNA-seq spatial transcriptomics. We investigated matched samples tissue pericardial fluid revealed...
Abstract Colorectal cancer is the third most common malignancy worldwide, with increasing numbers due to spreading obesity epidemic and Western diet. tumors are subclassed by mutational burden, caused microsatellite instability (MSI). MSI-high tend induce robust T-cell responses respond well immunotherapy. However, microsatellite-stable (MSS) lack high burden conventional recognition. While these have therefore been considered immunologically “cold,”, MSS infiltrated innate lymphocytes,...