A5017053574- Polyamine Metabolism and Applications
- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Pain Mechanisms and Treatments
- Plant nutrient uptake and metabolism
- Lymphoma Diagnosis and Treatment
- Clinical Nutrition and Gastroenterology
- Gastrointestinal motility and disorders
- Ubiquitin and proteasome pathways
- Anesthesia and Neurotoxicity Research
- Retinal Development and Disorders
- Respiratory Support and Mechanisms
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Hedgehog Signaling Pathway Studies
- Potato Plant Research
- Cancer, Stress, Anesthesia, and Immune Response
- Ovarian cancer diagnosis and treatment
- Venous Thromboembolism Diagnosis and Management
- Thermal Regulation in Medicine
- Central Venous Catheters and Hemodialysis
- Fungal and yeast genetics research
Massachusetts General Hospital
2022-2025
Harvard University
2017-2025
Howard Hughes Medical Institute
2014-2023
Whitehead Institute for Biomedical Research
2012-2017
Massachusetts Institute of Technology
2014-2017
Allen Institute
2014-2017
Broad Institute
2014-2017
Koch Institute for Integrative Cancer Research At MIT
2017
Yale University
2009
University of Guelph
2005
From sensing leucine to metabolic control The mTORC1 protein kinase complex plays central roles in regulating cell growth and metabolism is implicated common human diseases such as diabetes cancer. level of the amino acid tells an organism a lot about its physiological state, including how much food available, insulin going be needed, whether new muscle mass can made (see Perspective by Buel Blenis). Wolfson et al. identified biochemical sensor leucine, Sestrin2, which connects concentration...
Sensing amino acids at the lysosome The mTORC1 protein kinase is a complex of proteins that functions to regulate growth and metabolism. Activity sensitive abundance acids, but how sensing coupled control has been unclear. Wang et al. searched for predicted membrane interacted with regulators mTORC1. They identified currently known only as SLC38A9. Interaction SLC38A9 was presence acids. sequence similarity acid transporters. Effects modulation in cultured human cells indicate it may be...
The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator cell growth that responds to numerous environmental cues. A key input amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound RagC RagD) in order promote translocation mTORC1 lysosomal surface, its site activation. GATOR2 unknown function positively regulates signaling by acting upstream parallel GATOR1, GTPase-activating protein (GAP) for RagA and an inhibitor amino-acid-sensing...
From sensing leucine to metabolic control The mTORC1 protein kinase complex plays central roles in regulating cell growth and metabolism is implicated common human diseases such as diabetes cancer. level of the amino acid tells an organism a lot about its physiological state, including how much food available, insulin going be needed, whether new muscle mass can made (see Perspective by Buel Blenis). Wolfson et al. identified biochemical sensor leucine, Sestrin2, which connects concentration...
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets colon-innervating DRG with diverse morphologic physiologic properties. Four neuron populations mechanosensitive exhibit distinct force thresholds to distension. highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary...
To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies seriously ill patients suggest a beneficial morbidity, but no trials have examined possible benefits patients.Prospective, double-blind, randomized trial.Burn intensive care unit university hospital.Twenty-six severe burn with total surface area 25% to 90% and presence full-thickness burns. Patients were evaluated for...
Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models septic shock. Induction HSPs improve outcome in human disease not exploited because induction agents are themselves toxic and clinically relevant. In this study, we demonstrate that a single dose intravenous glutamine causes rapid significant increase HSP25 HSP72 multiple organs the unstressed Sprague-Dawley rat. With utilization fluid-resuscitated rat model endotoxemia, mortality was...
Clinical trials have demonstrated that glutamine (GLN) supplementation can decrease infectious morbidity and improve survival in a number of settings critical illness. The mechanism this protection remains unclear. objective study was to evaluate the effect GLN on cytokine release, organ injury, from endotoxininduced septic shock. Endotoxemia induced Male Sprague-Dawley rats by intravenous administration 5mg/kg Escherichia coli lipopolysaccharide (LPS). Concomitantly, animals were fluid...
Neuroblastoma is the most common pediatric extracranial solid tumor. Within conventional risk groups, there considerable heterogeneity in outcomes, indicating need for improved stratification.In this study we analyzed somatic mutational burden of 515 primary, untreated neuroblastoma tumors from three independent cohorts. Mutations coding regions were determined by whole-exome/genome sequencing tumor samples compared to matched blood leukocytes. Survival data 459 patients available analysis...
Abstract The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding their roles in normal physiology and gastrointestinal disease. Here, we report genetically defined subsets innervating DRG with diverse morphologic physiologic properties. Four neuron populations mechanosensitive exhibit distinct force thresholds to distension. highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary...