A5078858403- Connective tissue disorders research
- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- RNA Research and Splicing
- Liver physiology and pathology
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Fibroblast Growth Factor Research
- Organ Transplantation Techniques and Outcomes
- Circular RNAs in diseases
- Calpain Protease Function and Regulation
- Pregnancy and preeclampsia studies
- MicroRNA in disease regulation
- Cardiomyopathy and Myosin Studies
- Cardiovascular Issues in Pregnancy
- Cardiac Fibrosis and Remodeling
- Cardiovascular Effects of Exercise
- Signaling Pathways in Disease
- Congenital heart defects research
- Neuroinflammation and Neurodegeneration Mechanisms
Johns Hopkins University
2011-2024
Johns Hopkins Medicine
2011-2024
University of Baltimore
2022-2023
RNA polymerase II synthesizes a diverse set of transcripts including both protein-coding and non-coding RNAs. One major difference between these two classes is the mechanism termination. Messenger terminate downstream coding region in process that coupled to cleavage polyadenylation reactions. Non-coding like Saccharomyces cerevisiae snoRNAs requires RNA-binding proteins Nrd1, Nab3, Sen1. We report here transcriptome-wide distribution termination factors. These data sets derived from vivo...
The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors transforming growth factor-β (TGF-β) pathway. Using a mouse model Loeys-Dietz syndrome (LDS) that carries kinase-inactivating mutation TGF-β receptor I, we found effects this depend on lineage origin vascular smooth muscle cells (VSMCs). Secondary heart field–derived (SHF-derived), but not neighboring cardiac neural crest–derived (CNC-derived), VSMCs...
RNA polymerase II transcribes both coding and noncoding genes, termination of these different classes transcripts is facilitated by sets factors. Pre-mRNAs are terminated through a process that coupled to the cleavage/polyadenylation machinery, RNAs in yeast Saccharomyces cerevisiae pathway directed RNA-binding proteins Nrd1, Nab3, helicase Sen1. We have used an vivo cross-linking approach map binding sites components non-poly(A) pathway. show here Sen1 bind number unexpected manner. shows...
NF-κB and BRD4 epigenetically activate a TGFB2 enhancer to lock sclerotic patient fibroblasts into profibrotic synthetic state.
Human retinal organoid transplantation could potentially be a treatment for degenerative diseases. How the recipient retina regulates survival, maturation, and proliferation of transplanted cells is unknown. We human organoid-derived into photoreceptor-deficient mice conducted histology single-cell RNA sequencing alongside time-matched cultured organoids. Unexpectedly, we observed that migrated all layers traveled long distances. Using an unbiased approach, identified these as astrocytes...
Protection from pregnancy-associated aortic dissection is achieved by decreasing oxytocin-induced ERK signaling in a mouse model of Marfan syndrome.
Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress gene expression development miRNA-based therapeutics is being actively pursued for diverse array Because single miRNA can multiple genes, often within same...
Proliferative vitreoretinopathy (PVR) is the most common cause of failure retinal reattachment surgery, and molecular changes leading to this aberrant wound healing process are currently unknown. Our ultimate goal study PVR pathogenesis by employing single-cell transcriptomics dissect cellular heterogeneity.
Inhibition of calpain 9, a key mediator myofibroblast differentiation and tissue fibrosis, protects against fibrosis in preclinical models.
Heterozygous, loss of function mutations in positive regulators the Transforming Growth Factor-β (TGF-β) pathway cause hereditary forms thoracic aortic aneurysm. It is unclear whether and how initial signaling deficiency triggers secondary upregulation remaining functional branches pathway, if this contributes to maladaptive vascular remodeling. To examine process a mouse model which time-controlled, partial interference with postnatal TGF-β smooth muscle cells (VSMCs) could be assessed, we...
Angiotensin II (Ang II) type 1 receptor (AT1R) signaling controls both physiological and pathogenetic responses in the vasculature. In mouse models of Loeys-Dietz syndrome (LDS), a hereditary disorder characterized by aggressive aortic aneurysms, treatment with angiotensin blockers (ARBs) prevents root dilation associated histological alterations. this study we use germline conditional genetic inactivation Agtr1a (coding for AT1a receptor) to assess effect systemic localized AT1R attenuation...
Acute liver failure (ALF) affects 2000 Americans each year with no treatment options other than transplantation. We showed previously that mobilization of endogenous stem cells is protective against ALF in rodents. The objective this study was to assess whether cell mobilizing drugs are lifesaving a large animal preclinical model ALF, readiness for clinical trial.Male Yorkshire pigs (14-18 kg) were divided into 2 groups, control (n = 6) and 6). All received an intravenous bolus the...
Structured Abstract Purpose Proliferative vitreoretinopathy (PVR) is the most common cause of failure retinal reattachment surgery and molecular changes leading to this aberrant wound healing process currently unknown. We aimed study PVR pathogenesis using single-cell transcriptomics dissect cellular heterogeneity in a rabbit model. Methods was induced unilaterally Dutch Belted rabbits. At different timepoints following induction, retinas were dissociated into either cells or nuclei...
<title>Abstract</title> Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, aortic root a site of heightened risk. To identify molecular determinants this vulnerability, we investigated heterogeneity vascular smooth muscle cells (VSMCs) in aorta <italic>Tgfbr1<sup>M318R/+</sup></italic> LDS mice single cell and spatial transcriptomics. Reduced expression...
Loeys–Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing increase the risk of aneurysm throughout arterial tree, yet aortic root site heightened susceptibility. Here we investigate heterogeneity vascular smooth muscle cells (VSMCs) in aorta Tgfbr1M318R/+ LDS mice single-cell transcriptomics to identify molecular determinants this vulnerability. Reduced expression components extracellular matrix–receptor...
Abstract Human retinal organoid transplantation can potentially restore vision in patients with degenerative diseases. How the recipient retina regulates maturation, fate specification, and migration of transplanted cells is unknown. We human organoid-derived into photoreceptor-deficient mice, conducted histology single-cell RNA sequencing analyses, observed two main classes graft-derived cells. The first class consisted astrocytes brain/spinal cord-like neural precursors, absent or rare...
The pathogenesis of aortic aneurysms caused by mutations that impair TGF-β/Smad signaling without completely ablating it remains unclear. To investigate TGF-β’s role independently its developmental functions, we used mouse models to inactivate Smad3 specifically in smooth muscle cells (SMCs) at 6 weeks age, when postnatal matrix deposition is largely completed. This intervention was sufficient induce dilation the root, but not ascending aorta. identify factors underlying this regional...
Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by predisposition to aneurysm. Although dilation can develop in all segments of the arterial tree, aortic root especially prone disease. This region primarily composed vascular smooth muscle cells (VSMCs) derived from secondary heart field (SHF) progenitors, while VSMCs cardiac neural crest (CNC) predominate more distal ascending aorta. intrinsic differences have been found between these two types VSMCs, it remains...