A5012641122- Renal and Vascular Pathologies
- Cardiovascular Issues in Pregnancy
- Hormonal Regulation and Hypertension
- Birth, Development, and Health
- Aortic aneurysm repair treatments
- Pregnancy and preeclampsia studies
- Erythropoietin and Anemia Treatment
- Connective Tissue Growth Factor Research
- Atherosclerosis and Cardiovascular Diseases
- Hearing, Cochlea, Tinnitus, Genetics
- RNA and protein synthesis mechanisms
- Cardiac Structural Anomalies and Repair
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- Microbial metabolism and enzyme function
- Vascular anomalies and interventions
- Cerebrovascular and Carotid Artery Diseases
- Pulmonary Hypertension Research and Treatments
- Adrenal Hormones and Disorders
- COVID-19 Clinical Research Studies
- Coronary Artery Anomalies
- Abdominal vascular conditions and treatments
- Renin-Angiotensin System Studies
- Cardiovascular Disease and Adiposity
- Ferroptosis and cancer prognosis
Michigan Medicine
2014-2025
University of Michigan
2010-2024
Michigan United
2018-2024
Ann Arbor Center for Independent Living
2020
Milligan College
2019
Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal cerebrovascular arteries. FMD often an underdiagnosed cause of hypertension stroke, has higher prevalence in females (~80%) but its pathophysiology unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays 249 patients 689 controls. replicated 13 loci (P<10−4) 402 cases 2,537 controls confirmed association between variant...
Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers previously...
Abstract Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction (MI), typically in young women. We undertook genome-wide association study SCAD (N cases = 270/N controls 5,263) and identified replicated an rs12740679 at chromosome 1q21.2 ( P discovery+replication 2.19 × 10 −12 , OR 1.8) influencing ADAMTSL4 expression. Meta-analysis discovery replication samples associations with < 5 −8 6p24.1 PHACTR1 12q13.3 LRP1 females-only, 21q22.11 near...
Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain angiography. Inflammatory biomarkers in plasma transforming growth factor β (TGF-β) cytokines patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia multifocal stenosis included...
Men are disproportionately affected by the coronavirus disease-2019 (COVID-19), and face higher odds of severe illness death compared to women. The vascular effects androgen signaling inflammatory cytokines in acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial injury not defined. We determined SARS-CoV-2 spike protein-mediated under conditions exposure dihydrotestosterone (DHT) tumor necrosis factor-a (TNF-α) tested potentially therapeutic mineralocorticoid receptor...
Objective: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely arterial dissections, recurrent underlying a systemic arteriopathy not described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) previously defined. Approach Results: We studied 4 independent probands pathogenic variant c.1540G>A, p.(Gly514Ser) who presented aneurysms, tortuosity, mFMD affecting multiple arteries. Arterial medial fibroplasia smooth muscle...
Importance The emerging genetic basis of spontaneous coronary artery dissection (SCAD) has been defined as both partially complex and monogenic in some patients, involving variants predominantly genes known to underlie vascular connective tissue diseases (CTDs). effect these influences not high-risk SCAD phenotypes, the identification a subgroup individuals may help guide clinical evaluations SCAD. Objective To identify quantify burden rare variation with features. Design, Setting,...
Background: The risk of arterial diseases may be elevated among family members individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the in families with FMD. Methods: Family histories for 73 probands FMD were obtained, which included an analysis 463 total first-degree relatives focusing on and related disorders. A polygenic score (PRS ) was constructed from prior genome-wide association findings 584 cases 7139 controls evaluated abdominal aortic aneurysm...
Abstract Aims Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes elucidate molecular mechanisms implicated in FMD SCAD. Methods results analysed 29 exomes that included familial sporadic FMD. identified one loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two...
The inner ear is a complex organ containing sensory tissue, including hair cells, the development of which not well understood. Our long-term goal to discover genes critical for correct formation and function its tissue. A novel gene, transmembrane (Tmie), was found cause hearing-related disorders when defective in mice humans. homologous tmie gene zebrafish cloned expression characterized between 24 51 hours post-fertilization. Embryos injected with morpholinos (MO) directed against...
Hearing and balance depend upon the precise morphogenesis mechanosensory function of stereocilia, specialized structures on apical surface sensory hair cells in inner ear. Previous studies Grxcr1 mutant mice indicated a critical role for this gene control stereocilia dimensions during development. In study, we analyzed expression paralog Grxcr2 mouse evaluated auditory vestibular strains carrying targeted mutations gene. Peak occurs early postnatal development ear GRXCR2 is localized to both...
Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. associations with central SBP (cSBP) not well-studied. discovery most often in European-ancestry samples. Here, we investigated genetic cSBP a Chinese population functionally validated the impact novel associated coiled-coil domain containing 93 ( CCDC93 ) gene regulation. An...
Abstract Crosstalk between multiple components underlies the formation of mature vessels. Although players involved in angiogenesis have been identified, mechanisms underlying crosstalk them are still unclear. Using ex vivo aortic ring assay, we set out to dissect interactions two key angiogenic signaling pathways, vascular endothelial growth factor (VEGF) and transforming β (TGFβ), with members lysyl oxidase (LOX) family matrix modifying enzymes. We find an interplay VEGF, TGFβ, LOXs is...
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Abstract The etiology of renal artery stenosis (RAS) and abdominal aortic coarctation (AAC) causing the midaortic syndrome (MAS), often resulting in renovascular hypertension (RVH), remains ill-defined. Neurofibromatosis type 1 (NF-1) is frequently observed children with RVH. Consecutive pediatric patients (N = 102) presenting RVH secondary to RAS without concurrent AAC were prospectively enrolled a clinical data base, blood, saliva operative tissue, when available, collected. Among 102...
Vascular endothelial growth factor (VEGF) inhibition is linked to the development of hypertension and proteinuria in preeclampsia. This occurs as anti-angiogenic factors from placenta contribute pregnancy-related disorder. Soluble VEGF receptor fms-like tyrosine kinase-1 (sFLT-1) an that counteracts VEGF. Levels sFLT-1 are three times higher preeclamptic placentas compared those normotensive pregnancies, plasma levels increase with severity Infusing rodents induces hypertension, proteinuria,...
Abstract Objective: Fibromuscular dysplasia (FMD) is an arteriopathy that presents mainly by hypertension, stroke or dissection. Diagnosis often made in middle-aged women with few cardiovascular risk factors. We aim at identifying common genetic variants associated to FMD. Design and method: tested ∼6.5 million (MAF > 0.01) 1962 cases 7100 controls from 6 studies using gene-based association analyses. Participants were of European ancestry, similar characteristics (91% multifocal, 88%...
Background: Men are disproportionately affected by the coronavirus disease-2019 (COVID-19) and experience higher mortality as compared to women. The vascular effects of androgen signaling inflammatory cytokines in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial damage not defined.Methods: Here, we determined SARS-CoV-2 spike protein-mediated under conditions exposure androgens TNF-α. We tested therapeutic approved drugs: angiotensin receptor blockade...