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Principal Investigator: Amy Pate Patterson
Organization: CLINICAL CENTER
Fiscal Year: 2024
Funding agency: NIH Clinical Center
Regarding our research in lipid metabolism, we have demonstrated that SR-BI mediates LDL binding as well as cholesterol ester (CE) and triacylglycerol (TAG) sorting followed by their internalization to LDs. While about 60% of LDL- delivered neutral lipid (NL) to be uploaded to LDs requires neutral hydrolysis and de novo neutral lipid synthesis, about 40% is directly sorted and transported to LDs. Most importantly, both in vitro and in vivo data suggest that SR-BI is critical for short term LD formation from LDL in the liver and potentially other organs. Regarding coronary artery disease, collaboration with NHLBI, we have found an association of oxidized apoB and apoA-I with high-risk coronary plaque (PMID: 37698922).
Regarding our work in understanding APOBEC-3 regulation, we found that: 1) APOBEC3 induced HBV mutations occurred sequentially on HBV (-)-DNA from the reverse transcription start to termination site in parallel with the reverse transcription process;2) APOBEC3 mutation efficiency varied significantly with an order of A3B>>A3G>A3H-II or A3C with variation observed even with the same APOBEC3, suggesting the presence of other factors affecting APOBEC3 mutation activity; 3) Among APOBEC3s, A3B had a 3-fold higher mutation efficiency with up to 65% of cytidines being mutated, consistent with the kataegis-like A3B mutation signature in cancer. On the other hand, A3C had a unique higher mutation frequency on HBV genome populations with a preference for both 5TC and 5CC; and 4) APOBEC3 induced HBV mutation was detected in HBV rcDNA, not in cccDNA and pgRNA, suggesting that APOBEC3 induced mutation on HBV genomes occurs essentially as a singular event, occurring only within the nucleocapsid and involving rcDNA replication.
Regarding inflammation, in a collaboration with a U of MD group, we have published that age related accumulation of truncated oxidized phospholipids augments infectious lung injury and endothelial dysfunction (PMID 37566016). In addition with this group, we published this year that the peptide L37pA protects against lung vascular endothelial dysfunction caused by truncated oxidized phospholipids through CD36 antagonism (PMID:37725486).
We have begun to evaluate the role of class B scavenger receptors in the pathogenesis of SARS-CoV-2.In a collaboration with NEI, we have published (PMID:37511618) that the low density lipoprotein receptor (LDLR) is involved with SARS-CoV-2 spike protein mediated uptake in ocular cells.
We are evaluating the role of class B scavenger receptors in ApoL1 variant associated kidney diseases.
Terms: <2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><APOL-I><APOL1><APOL1 gene><Affect><African Sleeping Sickness><African Trypanosomiasis><Apo A-1><Apo A-I><Apo A1><Apo AI><Apo-B><ApoA-1><ApoA-I><ApoB><Apolipoprotein A-1><Apolipoprotein A-I><Apolipoprotein A1><Apolipoprotein AI><Apolipoproteins><Apolipoproteins B><Atherosclerosis><Atherosclerotic Cardiovascular Disease><Biology><Blood Vessels><Body Tissues><CD36><CD36 gene><COVID-19 S protein><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><Cancers><Cardiovascular Diseases><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cholesterol Esters><Cholesteryl Esters><Chronic><Clinical><Collaborations><Coronary Arteriosclerosis><Coronary Artery Disease><Coronary Artery Disorder><Coronary Atherosclerosis><Cytidine><Cytosine Ribonucleoside><Cytosine Riboside><DNA><Data><Defense Mechanisms><Deoxyribonucleic Acid><Development><Event><Family><Frequencies><GP3B><GP4><GPIV><Genetic Alteration><Genetic Change><Genetic defect><Genome><HBV><HDL><HDL Lipoproteins><Heavy Lipoproteins><Hepatitis B Virus><High Density Lipoproteins><High density lipoprotein><Homologous Serum Hepatitis Virus><Host Defense><Host Defense Mechanism><Human><Hydrolysis><Immunity><In Vitro><Induced DNA Alteration><Induced Mutation><Induced Sequence Alteration><Infection><Inflammation><Innate Immune Response><Innate Immune System><Innate Immunity><Integral Membrane Protein><Intermediary Metabolism><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Intrinsic Membrane Protein><Investigation><Kidney><Kidney Diseases><Kidney Urinary System><LDL><LDL Lipoproteins><LDL Receptors><Link><Lipids><Lipoprotein Binding><Lipoprotein LDL Receptors><Lipoprotein Receptor><Lipoproteins><Liver><Low Density Lipoprotein Receptor><Low-Density Lipoproteins><Lung><Lung Respiratory System><Lung damage><Lytic><Malignant><Malignant - descriptor><Malignant Neoplasms><Malignant Tumor><Mediating><Messenger RNA><Metabolic Processes><Metabolic syndrome><Metabolism><Modern Man><Molecular><Mutate><Mutation><NHLBI><National Heart, Lung, and Blood Institute><Native Immunity><Natural Immunity><Nephropathy><Non-Specific Immunity><Nonspecific Immunity><Nucleocapsid><Organ><Parasites><Pathologic><Pathway interactions><Pattern><Peptides><Phosphatides><Phospholipids><Physiologic><Physiological><Play><Population><Protein Family><Proteins><Publishing><RNA Splicing><Receptor Protein><Regulation><Renal Disease><Research><Reverse Transcription><Rhodesian trypanosome><Risk><Role><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 pathogenesis><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SCARB3><SR-B proteins><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Signal Transduction><Signal Transduction Systems><Signaling><Site><Sorting><Splicing><T rhodesiense><T. rhodesiense><T.rhodesiense><Therapeutic><Tissues><Transcription Process><Transmembrane Protein><Transmembrane Protein Gene><Triacylglycerol><Triglycerides><Trypanosoma><Trypanosoma brucei rhodesiense><Trypanosoma rhodesiense><Trypanosome><Urd><Uridine><Variant><Variation><Viral Cancer><Viral Diseases><Virus Diseases><Work><age associated><age correlated><age dependent><age linked><age related><age specific><alpha-Lipoproteins><antagonism><antagonist><atheromatosis><atherosclerotic coronary disease><atherosclerotic disease><atherosclerotic vascular disease><beta-Lipoproteins><biological signal transduction><cardiovascular disorder><class B scavenger receptors><coronary arterial disease><coronary plaque><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><developmental><endothelial dysfunction><fat metabolism><fatty acid transport><genome mutation><hepatic body system><hepatic organ system><high risk><in vivo><interventional strategy><kidney disorder><lipid metabolism><lung injury><mRNA><malignancy><neoplasm/cancer><particle><pathogen><pathway><pgRNA><polypeptide><preference><prevent><preventing><prophylactic><protein function><psychological defense mechanism><pulmonary><pulmonary damage><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><receptor><renal><renal disorder><severe acute respiratory syndrome coronavirus 2 pathogenesis><sleeping sickness><social role><spike proteins on SARS-CoV-2><therapeutic target><uptake><vascular><vascular endothelial dysfunction><viral infection><virus infection><virus-induced disease>