A5024718512- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Caveolin-1 and cellular processes
- Immune Response and Inflammation
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Platelet Disorders and Treatments
- Barrier Structure and Function Studies
- Cerebrovascular and Carotid Artery Diseases
- Acute Ischemic Stroke Management
- Cardiomyopathy and Myosin Studies
- Cancer Research and Treatments
- Inflammatory mediators and NSAID effects
- Sphingolipid Metabolism and Signaling
- Intracranial Aneurysms: Treatment and Complications
- Intensive Care Unit Cognitive Disorders
- Endoplasmic Reticulum Stress and Disease
- Cerebrovascular and genetic disorders
- Trypanosoma species research and implications
- Moyamoya disease diagnosis and treatment
Northwestern University
2016-2025
Northwestern Medicine
2018-2025
Northwestern University
2023
Midwestern University
2021
Respiratory Clinical Trials
2020
National Health and Medical Research Council
2020
Cornell University
2006-2018
Simon Fraser University
2005
University of Wisconsin–Madison
2003
California Institute of Technology
2003
Neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). To assess the PMN phenotypic functional diversification during inflammatory ulceration to CRC transition we analyzed transcriptomic landscape blood PMNs. Transcriptional programs effectively separated PMNs based on their localization peripheral blood, inflamed colon, tumors. In silico pathway overrepresentation analysis, protein-network mapping, gene signature...
The mechanism by which newly synthesized sterols are transported from their site of synthesis, the endoplasmic reticulum (ER), to sterol-enriched plasma membrane (PM) is not fully understood. Studies in mammalian cells suggest that cholesterol PM Golgi-bypassing vesicles and/or via a nonvesicular process. Using yeast Saccharomyces cerevisiae as model system, we now rule out an essential role for known vesicular transport pathways transporting major sterol, ergosterol, its synthesis PM. We...
Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby creating contact sites that are proposed form platforms for regulating lipid homeostasis and facilitating non-vesicular exchange. Sterols synthesized in ER transported by mechanisms plasma membrane (PM), where they represent almost half of all PM lipids contribute critically barrier function PM. To determine whether important both sterol exchange between intermembrane regulation metabolism, we...
Sterol transport between the endoplasmic reticulum (ER) and plasma membrane (PM) occurs by an ATP-dependent, non-vesicular mechanism that is presumed to require sterol proteins (STPs). In Saccharomyces cerevisiae, homologs of mammalian oxysterol-binding protein (Osh1-7) have been proposed function as STPs. To evaluate this proposal we took two approaches. First used dehydroergosterol (DHE) visualize movement in living cells fluorescence microscopy. DHE was introduced into PM under hypoxic...
Vascular aging impacts multiple organ systems, including the brain, where it can lead to vascular dementia. However, a concrete understanding of how specifically affects brain vasculature, along with molecular read-outs, remain vastly incomplete. Here we demonstrate that is associated marked decline in Notch3 signaling both murine and human vessels. To clarify consequences loss used single-cell transcriptomics uncovered inactivation alters regulation calcium, contractile function, promotes...
Transbilayer lipid asymmetry is a fundamental characteristic of the eukaryotic cell plasma membrane (PM). While PM phospholipid well documented, transbilayer distribution sterols such as mammalian cholesterol and yeast ergosterol not reliably known. We now report that are asymmetrically distributed across PM, with majority (~80%) located in cytoplasmic leaflet. By exploiting sterol‐auxotrophic hem1 Δ strain we obtained cells which endogenous was quantitatively replaced dehydroergosterol...
Hypoxia-inducible factors (HIFs) are activated in parenchymal cells response to low oxygen and as such have been proposed therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs also within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics development for cardiac ischemic injury, surprisingly, unique role of myeloid HIFs, particularly HIF-2α, is unknown. Using a murine model mice with conditional genetic loss gain...
Neutrophil (PMN) mobilization to sites of insult is critical for host defense and requires transendothelial migration (TEM). TEM involves several well-studied sequential adhesive interactions with vascular endothelial cells (ECs); however, what initiates or terminates this process not well-understood. Here we describe believe be a new mechanism where vessel associated macrophages (VAMs) through localized primed EC responses form ICAM-1 "hot spots", support PMN TEM. Using real-time intravital...
The movement of leukocytes across endothelium [referred to as diapedesis or transendothelial migration (TEM)] is a critical step in the inflammatory process. Recently, it was demonstrated that treatment endothelial cells and monocytes with antibodies against poliovirus receptor (PVR; CD155) DNAX-associated molecule-1 (DNAM-1; CD226) arrested over junctions prevented TEM, suggesting these molecules are involved diapedesis. However, nothing known about mechanism by which PVR DNAM-1 work TEM....
Introduction: Polymorphonuclear leukocytes (PMNs) are among the first recruited to infarct following reperfusion in ischemic stroke. Although transendothelial migration (TEM) blockade preclinical studies was found reduce size, TEM clinical trials has been unsuccessful. Studying PMN recruitment and lifespan stroke may offer insight into these failures advance therapeutic development. Methods: PMNs were briefly pulse-labeled with 5-Ethynyl-2’-deoxyuridine (EdU) determine pattern...
Introduction: The cranial bone marrow has been recognized as a potential reservoir for myeloid cells, capable of entering the cerebral cortex through direct channels connecting skull and cortical surface brain. significance marrow-derived leukocytes following ischemic stroke in setting ischemia/reperfusion remains uncertain. We sought to characterize fraction injury using murine transient middle artery occlusion (tMCAO) model. Methods: C57BL/6 LysM-GFP (green neutrophils monocytes) mice...
All glioblastoma (GBM) molecular subsets share the common trait of accelerated progression following necrosis, which cannot be adequately explained by cellular proliferation arising from accumulated genetic alterations. Counter to dogma that “cancer outgrows its blood supply,” we suggest development necrosis is not merely a consequence aggressive neoplastic growth but could contributing force causing tumor microenvironment (TME) restructuring and biologic progression. Mechanisms related...
We longitudinally imaged both the superficial and deep cortical microvascular networks in brains of healthy mice a mouse model stroke vivo using visible-light optical coherence tomography (vis-OCT). surgically implanted microprism sealed by chronic cranial window. The enabled vis-OCT to image entire depth cortex. Following implantation, we for 28 days found that it took around 15 microvessels recover from implantation surgery. After recovered, introduced ischemic strokes transient middle...
Neutrophil (PMN) recruitment to sites of insult is critical for host defense, however excessive PMN activity and tissue accumulation can lead exacerbated inflammation injury. Myeloperoxidase (MPO) a azurophilic granule enzyme, which together with H 2 O , forms powerful antimicrobial system designed kill ingested bacteria. Intriguingly, in addition intracellular killing invading microorganisms extracellular damage due generation ROS, soluble MPO has been directly implicated modulating...
Abstract Leukocyte trafficking into the CNS is a prominent feature driving immunopathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Blocking recruitment inflammatory leukocytes represents an exploitable therapeutic target; however, adhesion molecules that specifically regulate step leukocyte diapedesis remain poorly understood. We report CD99 critical for lymphocyte transmigration without affecting in human blood–brain barrier model. blockade...
A polyamide−peptide conjugate is designed which recruits sequence specifically the developmental regulator Exd to a cognate DNA site. In particular, an eight-ring hairpin polyamide (Im-Im-Py(C3H6NHR)-Py-γ-Im-Py-Py-Py-β-Dp) with heptapeptide (R = Ac-Phe-Tyr-Pro-Trp-Met-Lys-Gly-) attached on central ring was shown induce cooperative binding of Drosophila Hox protein cofactor Kd 4.4 nM in vitro, order magnitude more efficient than natural partner Ubx. The joins two specific domains, one for and...
Endothelial cell calcium flux is critical for leukocyte transendothelial migration (TEM), which in turn essential the inflammatory response. Intravital microscopy of endothelial dynamics reveals that increases locally and transiently around transmigration pore during TEM. calmodulin (CaM), a key signaling protein, interacts with IQ domain IQGAP1, localized to junctions required In presence calcium, CaM binds calcium/calmodulin kinase IIδ (CaMKIIδ). Disrupting function or CaMKII...