A5032848960- Angiogenesis and VEGF in Cancer
- Developmental Biology and Gene Regulation
- Pregnancy and preeclampsia studies
- Epigenetics and DNA Methylation
- Cardiovascular Function and Risk Factors
- Histone Deacetylase Inhibitors Research
- Diabetes Treatment and Management
- Cancer-related Molecular Pathways
- Chemotherapy-induced cardiotoxicity and mitigation
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Neonatal Respiratory Health Research
- Signaling Pathways in Disease
- Renal and related cancers
- Genetics, Aging, and Longevity in Model Organisms
- Childhood Cancer Survivors' Quality of Life
- Protease and Inhibitor Mechanisms
- Fetal and Pediatric Neurological Disorders
- Diabetes Management and Research
- Kruppel-like factors research
- Caveolin-1 and cellular processes
- BRCA gene mutations in cancer
- Cerebrospinal fluid and hydrocephalus
- Cerebrovascular and genetic disorders
- Colorectal and Anal Carcinomas
Cambridge University Hospitals NHS Foundation Trust
2023
St. Michael's Hospital
2018-2020
University of Toronto
2018-2020
McMaster University
2020
German Cancer Research Center
2010-2018
Heidelberg University
2010-2018
St Michaels Hospital
2018
Landscape Research Group
2016
Hôpital Edouard Herriot
2016
Hospices Civils de Lyon
2016
Rationale: The ICAP1 (integrin cytoplasmic domain–associated protein-1) is a specific intracellular binding protein of β1-integrins and the cerebral cavernous malformation (CCM) CCM1. recruits CCM1 to cell membrane activates by changing its conformation. Because plays critical role for cardiovascular development, we hypothesized that activator involved in vascular differentiation. Objective: objective this study was define endothelial cells. Methods Results: Loss primary human cells causes...
Abstract Hydrocephalus is a common congenital anomaly. LCAM 1 and MPDZ ( MUPP ) are the only known human gene loci associated with non‐syndromic hydrocephalus. To investigate functions of tight junction‐associated protein Mpdz, we generated mouse models. Global Mpdz deletion or conditional inactivation in Nestin‐positive cells led to formation supratentorial hydrocephalus early postnatal period. Blood vessels, epithelial choroid plexus, cilia on ependymal cells, which line ventricular...
The placenta, a tissue that is metabolically active and rich in mitochondria, forms critical interface between the mother developing fetus. Oxidative stress within this tissue, derived from dysregulation of reactive oxygen species (ROS), has been linked to number adverse fetal outcomes. While such outcomes have associated with mitochondrial dysfunction, causal role dysfunction mitochondrially generated ROS altering process placentation remains unclear. In study, complex I activity was...
The formation of novel blood vessels is initiated by vascular endothelial growth factor. Subsequently, DLL4-Notch signaling controls the selection tip cells, which guide new sprouts, and trailing stalk cells. Notch in cells induced DLL4 on Moreover, DLL1 are expressed cell plexus to maintain signaling. loss-of-function causes a hyperdense network with disturbed flow.This study was aimed at identifying modifiers that interact intracellular domains DLL4.Synaptojanin-2 binding protein (SYNJ2BP,...
Abstract Intraflagellar transport protein 88 (Ift88) is required for ciliogenesis and shear stress-induced dissolution of cilia in embryonic endothelial cells coincides with endothelial-to-mesenchymal transition (EndMT) the developing heart. EndMT also suggested to underlie heart lung fibrosis, however, mechanism linking Ift88, its effect on organ fibrosis remains mainly unexplored. We silenced Ift88 (ECs) vitro generated cell-specific Ift88-knockout mice (Ift88 endo ) vivo evaluate...
Angiogenesis is coordinated by VEGF and Notch signaling. DLL4-induced signaling inhibits tip cell formation vessel branching. To ensure proper signaling, receptors ligands are clustered at adherens junctions. However, little known about factors that control activity influencing the cellular localization of ligands. Here, we show multiple PDZ domain protein (MPDZ) enhances activity. MPDZ physically interacts with intracellular carboxyterminus DLL1 DLL4 enables their interaction junction...
Seven-in-absentia homolog (SIAH) proteins are evolutionary conserved RING type E3 ubiquitin ligases responsible for the degradation of key molecules regulating DNA damage response, hypoxic adaptation, apoptosis, angiogenesis, and cell proliferation. Many studies suggest a tumorigenic role SIAH2. In breast cancer patients SIAH2 expression levels correlate with aggressiveness overall patient survival. addition, SIAH inhibition reduced metastasis in melanoma. The SIAH1 is still ambiguous; both...
Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is widely used anticonvulsant drug that currently undergoing clinical evaluation for anticancer therapy due to its anti-angiogenic potential. Endothelial cells (ECs) can transition into mesenchymal and this form of EC plasticity called endothelial-to-mesenchymal (EndMT), which implicated in several pathologies including cancer organ fibrosis. However, the effect VPA on EndMT remains completely unknown. We report herein...
Abstract The human placental barrier facilitates many key functions during pregnancy, most notably the exchange of all substances between mother and fetus. However, preclinical models often lacked multiple cell layers, syncytialization trophoblast cells low oxygen levels that are present within body. Therefore, we aimed to design develop an in vitro model would reinstate these factors enable improved investigations function. BeWo trophoblastic umbilical vein endothelial were co-cultured on...
Notch signalling is essential for blood vessel formation. During angiogenesis, the ligand DLL4 on leading tip cell activates receptors adjacent stalk cells. DLL4-Notch impaired by JAG1 in endothelial The Delta/Serrate/Lag2 (DSL) domain of ligands binds to EGF-like repeats 11–13 receptor. This study aimed elucidate how soluble proteins containing these short domains interfere with during angiogenesis. Adenoviral vectors were generated express DSL DLL1, DLL4, JAG1, and Notch1 fused...
Mutations in the tumor suppressor gene BRCA2 (BReast CAncer susceptibility 2) predispose carriers to breast, ovarian, and other cancers. In response DNA damage, participates homology-directed damage repair maintain genome stability. Genome-wide association studies have identified an between single nucleotide polymorphisms plasma-lipid levels lipid deregulation humans. To date, apoptosis, are recognized as central pathways for endothelial dysfunction atherosclerosis; however, role of remains...
The Delta-Notch pathway is a signal exchanger between adjacent cells to regulate numerous differentiation steps during embryonic development. Blood vessel formation by sprouting angiogenesis requires high expression of the Notch ligand DLL4 in leading tip cell, while receptors trailing stalk are activated achieve strong signaling activity. Upon binding, cleaved ADAM proteases and gamma-secretase. This releases intracellular domain that acts as transcription factor. There evidence also...
Abstract Background The benefit of neoadjuvant chemotherapy (NCT) for early-stage oesophageal cancer is unknown. aim this study was to assess whether NCT improves the outcome patients with stage I or II disease. Methods Data were collected from 30 European centres 2000 2010. Patients who received compared underwent primary surgery regard postoperative morbidity, mortality, and overall disease-free survival. Propensity score matching used adjust differences in baseline characteristics....
Abstract Introduction Doxorubicin is amongst the most widely prescribed chemotherapy drugs due to its effectiveness in cancer treatment. However, progressive treatment using doxorubicin severely increases risk of congestive heart failure. Mechanistically, researchers have shown that (i) intercalates into DNA and disrupts topoisomerase-II-mediated repair (ii) generates free radicals which then causes damage cellular membranes, DNA, proteins. Ultimately these insults induce cardiomyocyte (CM)...