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Identifying novel microproteins and protein translation mechanisms involved in the development of atherosclerosis

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT Bile acids have been implicated as a contributor to atherosclerosis and is commonly found to be elevated in patients with metabolic disorders and cardiovascular disease (CVD). Recently, we observed extrahepatic bile acid release in high-fat/high-sucrose (HFHS) fed and LDLR KO pig models of atherosclerosis. To reveal novel targets to treat BA abnormality in patients with CVD, we aim to use the deep-sequencing technique, ribosome profiling (ribo-seq), to investigate translational control of BA synthesizing and trafficking genes in colon, kidney, liver, and muscle in HFHS-fed and LDLR KO atherogenic pig models (Aim 1). Additionally, Ribo-seq can be used to identify small open reading frames (smORFs) which encode microprotiens. These microprotiens are often overlooked and underappreciated as key players in biology and are highly enriched in mitochondria and often found to perturb metabolic processes. Thus, we aim to filter Ribo-seq data for smORFs encoding mitochondrial microproteins and determine their impacts on cellular metabolism using untargeted metabolomics/lipidomics followed by relevant stable isotope tracing to identify affected enzymes/pathways.

Up to $43K

2028-09-29

health research

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Identifying novel microproteins and protein translation mechanisms involved in the development of atherosclerosis

Identifying novel regulators of Tfh cell differentiation that can be targeted to improve humoral immunity during chronic viral infection

Identifying regulatory mechanisms of ROS1 signaling

Identifying Residual Connectivity in Veterans with Spinal Cord Injury for Precision Neurorehabilitation

Identifying signaling networks that contribute to Th17-mediated neuroinflammation

Identifying spatial tumor microenvironment signatures for risk stratification in primary melanoma

Identifying targets to mitigate immunotherapy-associated immune-related adverse events

Identifying the functional impact of ZNF688 autoantibodies in oral lupus lesions

Identifying the genetic causes of stillbirth using C. elegans as an in vivo platform

Identifying the mechanism(s) of scarless corneal wound healing in Acomys cahirinus (The African Spiny mice) and Mus musculus

Identifying the Specific Reward Processes Underlying the Maintenance of Binge-Eating Disorder using EEG and EMA

Identifying Translational Measures of Osteoarthritic Pain Between Preclinical Models and Patients

Identity and Function of Neurons Receiving Bottom-Up or Top-Down Inputs in the Adult and Developing V1

Idiographic Modeling of Loneliness: Testing a Theory of Social Homeostasis

IDOT TRANSPORTATION FUNDS

IDRC Middle East Programs

IEDC Technology & Innovation Grants

IEEE Foundation STEM Education Grants

IFB SPECIALIZED BALLOT PROOFING AND LANGUAGE MANAGEMENT SERVICES

IGVF Data and Coordinating Center (U24 Clinical trials Not Allowed)

IHS Behavioral Health Programs

IHS Community Health Representative Program

IHS Health Care Facilities Construction Program

IHS Sanitation Facilities Construction Program

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Grants

Identifying novel microproteins and protein translation mechanisms involved in the development of atherosclerosis

Identifying novel regulators of Tfh cell differentiation that can be targeted to improve humoral immunity during chronic viral infection

Identifying regulatory mechanisms of ROS1 signaling

Identifying Residual Connectivity in Veterans with Spinal Cord Injury for Precision Neurorehabilitation

Identifying signaling networks that contribute to Th17-mediated neuroinflammation

Identifying spatial tumor microenvironment signatures for risk stratification in primary melanoma

Identifying targets to mitigate immunotherapy-associated immune-related adverse events

Identifying the functional impact of ZNF688 autoantibodies in oral lupus lesions

Identifying the genetic causes of stillbirth using C. elegans as an in vivo platform

Identifying the mechanism(s) of scarless corneal wound healing in Acomys cahirinus (The African Spiny mice) and Mus musculus

Identifying the Specific Reward Processes Underlying the Maintenance of Binge-Eating Disorder using EEG and EMA

Identifying Translational Measures of Osteoarthritic Pain Between Preclinical Models and Patients

Identity and Function of Neurons Receiving Bottom-Up or Top-Down Inputs in the Adult and Developing V1

Idiographic Modeling of Loneliness: Testing a Theory of Social Homeostasis

IDOT TRANSPORTATION FUNDS

IDRC Middle East Programs

IEDC Technology & Innovation Grants

IEEE Foundation STEM Education Grants

IFB SPECIALIZED BALLOT PROOFING AND LANGUAGE MANAGEMENT SERVICES

IGVF Data and Coordinating Center (U24 Clinical trials Not Allowed)

IHS Behavioral Health Programs

IHS Community Health Representative Program

IHS Health Care Facilities Construction Program

IHS Sanitation Facilities Construction Program