Center for Vascular Biology

CVB publications

• Origins of Aortic Coarctation: A Vascular Smooth Muscle Compartment Boundary Model April 23, 2025
  Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs), such boundaries produce mosaic patterns of investment based on embryonic origins with important implications […]
  Christina L Greene
• Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects April 16, 2025
  Mutations in the TARDBP gene encoding TDP-43 protein are linked to loss of function in neurons and familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We recently identified reduced nuclear TDP-43 in capillary endothelial cells (ECs) of donors with ALS-FTD. Because blood-brain barrier (BBB) permeability increases in ALS-FTD, we postulated that reduced nuclear TDP-43 […]
  Ashok Cheemala
• Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration March 15, 2025
  Endothelial cells (ECs) help maintain the blood-brain barrier but deteriorate in many neurodegenerative disorders. Here we show, using a specialized method to isolate EC and microglial nuclei from postmortem human cortex (92 donors, 50 male and 42 female, aged 20-98 years), that intranuclear cellular indexing of transcriptomes and epitopes enables simultaneous profiling of nuclear proteins […]
  Omar M F Omar
• Repurposing of PSMA-targeted diagnostic and therapeutic agents for the detection and treatment of giant cell tumors of bone December 2, 2024
  Giant cell tumor of bone (GCTB) is a rare bone tumor often necessitating surgical intervention, radiation therapy, or treatment with bisphosphonates or denosumab. ^(99m)Tc-MDP bone scintigraphy for GCTB has limited specificity, and the relatively high uptake of ^(18)F-FDG in GCTB makes it challenging to differentiate it from other benign bone tumors. More specific detection and […]
  Brenna C McAllister
• Development and utilization of <em>Treponema pallidum</em> expressing green fluorescent protein to study spirochete-host interactions and antibody-mediated clearance: expanding the toolbox for syphilis research November 29, 2024
  Syphilis is a sexually transmitted infection caused by the highly invasive and immunoevasive spirochetal pathogen Treponema pallidum subsp. pallidum (TPA). Untreated syphilis can lead to infection of multiple organ systems, including the central nervous system. The alarming increase in syphilis cases globally underscores the importance of developing novel strategies to understand the complexities of syphilis […]
  Kristina N Delgado
• Development and utilization of <em>Treponema pallidum</em> expressing green fluorescent protein to study spirochete-host interactions and antibody-mediated clearance: expanding the toolbox for syphilis research November 1, 2024
  Syphilis is a sexually transmitted infection caused by the highly invasive and immunoevasive spirochetal pathogen Treponema pallidum subsp. pallidum (TPA). Untreated syphilis can lead to infection of multiple organ systems, including the central nervous system. The alarming increase in syphilis cases globally underscores the importance of developing novel strategies to understand the complexities of syphilis […]
  Kristina N Delgado
• Autoregulated splicing of <em>TRA2</em>β programs T cell fate in response to antigen-receptor stimulation September 12, 2024
  T cell receptor (TCR) sensitivity to peptide-major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the […]
  Timofey A Karginov
• Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses January 24, 2024
  Astrocyte activation is associated with neuropathology and the production of tissue inhibitor of metalloproteinase-1 (TIMP1). TIMP1 is a pleiotropic extracellular protein that functions both as a protease inhibitor and as a growth factor. Astrocytes that lack expression of Timp1 do not support rat oligodendrocyte progenitor cell (rOPC) differentiation, and adult global Timp1 knockout (Timp1^(KO)) mice […]
  Pearl A Sutter
• Targeted inCITE-Seq Analysis Identifies the Loss of Nuclear TDP-43 in Endothelium as a Mediator of Blood Brain Barrier Signaling Pathway Dysfunction in Neurodegeneration January 3, 2024
  Despite the importance of the endothelium in the regulation of the blood brain barrier (BBB) in aging and neurodegenerative disease, difficulties in extracting endothelial cell (EC) nuclei have limited analysis of these cells. In addition, nearly all Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD), and a large portion of Alzheimer's Disease (AD) exhibit neuronal […]
  Omar M F Omar
• Loss of Endothelial TDP-43 Leads to Blood Brain Barrier Defects in Mouse Models of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia January 3, 2024
  Loss of nuclear TDP-43 occurs in a wide range of neurodegenerative diseases, and specific mutations in the TARDBP gene that encodes the protein are linked to familial Frontal Temporal Lobar Dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS). Although the focus has been on neuronal cell dysfunction caused by TDP-43 variants, TARDBP mRNA transcripts are expressed […]
  Ashok Cheemala
• The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins December 27, 2023
  Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant […]
  Mallika Ghosh
• Higher HDL cholesterol levels are associated with increased markers of interstitial myocardial fibrosis in the MultiEthnic Study of Atherosclerosis (MESA) November 18, 2023
  Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease (CVD) outcomes. Yet, there is no data on HDL-C's association with other CVD risk factors like myocardial fibrosis, a key aspect of cardiac remodeling predicting negative outcomes. We therefore aimed to study the association between HDL-C levels with interstitial myocardial […]
  Omar Chehab
• The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection October 16, 2023
  Ab-mediated rejection of organ transplants remains a stubborn, frequent problem affecting patient quality of life, graft function, and grant survival, and for which few efficacious therapies currently exist. Although the field has gained considerable knowledge over the last two decades on how anti-HLA Abs cause acute tissue injury and promote inflammation, there has been a […]
  Adriana Franco-Acevedo
• Higher HDL Cholesterol Levels Are Associated with Increased Markers of Interstitial Myocardial Fibrosis: Insights from The Multi-Ethnic Study of Atherosclerosis October 4, 2023
  CONCLUSIONS: Increasing levels of HDL-C were associated with increased markers of IMF, with those with high levels of HDL-C being linked to subclinical fibrosis in a community-based setting.
  Omar Chehab
• Prolonged hypoxia alleviates prolyl hydroxylation-mediated suppression of RIPK1 to promote necroptosis and inflammation July 3, 2023
  The prolyl hydroxylation of hypoxia-inducible factor 1α (HIF-1α) mediated by the EGLN-pVHL pathway represents a classic signalling mechanism that mediates cellular adaptation under hypoxia. Here we identify RIPK1, a known regulator of cell death mediated by tumour necrosis factor receptor 1 (TNFR1), as a target of EGLN1-pVHL. Prolyl hydroxylation of RIPK1 mediated by EGLN1 promotes […]
  Tao Zhang
• Assessment of diversity-based approaches used by American Universities to increase recruitment and retention of biomedical sciences research faculty members: A scoping review protocol June 22, 2023
  Diversity enriches the educational experience by improving intellectual engagement, self-motivation, citizenship, cultural engagement, and academic skills like critical thinking, problem-solving, and writing for students of all races. Faculty role models from similar backgrounds are essential for students from traditionally underrepresented groups as it sends a powerful message of support, belonging, and the confidence to pursue […]
  Britta Petersen
• Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer May 25, 2023
  Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, […]
  Mathangi Madhavan
• LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice January 13, 2023
  CONCLUSIONS: Loss of LAG3 function promoted T cell activation and accumulation in plaques while not affecting plaque burden. Our report supports further clinical studies investigating cardiovascular risk in patients treated with anti-LAG3 ICB.
  Megan Mulholland
• Therapeutic potential of targeting mirnas to prostate cancer tumors: using psma as an active target October 31, 2022
  Prostate cancer (PC) is a commonly diagnosed malignancy in men and is associated with high mortality rates. Current treatments for PC include surgery, chemotherapy, and radiation therapy. However, recent advances in targeted delivery systems have yielded promising new approaches to PC treatment. As PC epithelial cells express high levels of prostate-specific membrane antigen (PSMA) on […]
  Amir Yarahmadi
• PLCβ2 Promotes VEGF-Induced Vascular Permeability July 21, 2022
  CONCLUSIONS: The results implicate PLCβ2 as a key positive regulator of VEGF-induced vascular permeability through regulation of both calcium flux and phosphatidylinositol 4,5-bisphosphate levels at the cellular level. Targeting of PLCβ2 in a therapeutic setting may provide a novel approach to regulating vascular permeability in patients.
  Kathryn N Phoenix