A5054832727- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced MRI Techniques and Applications
- Immunotherapy and Immune Responses
- Advanced Neuroimaging Techniques and Applications
- CAR-T cell therapy research
- Traumatic Brain Injury and Neurovascular Disturbances
- Neonatal and fetal brain pathology
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Neurological Disease Mechanisms and Treatments
- Transplantation: Methods and Outcomes
- Neurogenesis and neuroplasticity mechanisms
- Cardiac Arrest and Resuscitation
- Urinary Bladder and Prostate Research
- Hemoglobinopathies and Related Disorders
- Cardiac Imaging and Diagnostics
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Bladder and Urothelial Cancer Treatments
- MRI in cancer diagnosis
- Advanced Electron Microscopy Techniques and Applications
- Viral Infections and Immunology Research
University of Pittsburgh
2006-2024
Imaging Center
2016-2024
University of Miami
2024
University of Pittsburgh Medical Center
2023-2024
UPMC Hillman Cancer Center
2023-2024
McGowan Institute for Regenerative Medicine
2022-2023
Advanced Imaging Research (United States)
2020
Carnegie Mellon University
2006-2019
VA Pittsburgh Healthcare System
2013
University of Louisville
2008
In vivo cell tracking by MRI can provide means to observe biological processes and monitor therapy directly. Immune cells, e.g., macrophages, play crucial roles in many pathophysiological processes, including organ rejection, inflammation, autoimmune diseases, cancer, atherosclerotic plaque formation, numerous neurological disorders, etc. The current gold standard for diagnosing staging rejection after transplantation is biopsy, which not only invasive, but also prone sampling errors. Here,...
Persistent endoplasmic reticulum (ER) stress in neurons is associated with activation of inflammatory cells and subsequent neuroinflammation following traumatic brain injury (TBI); however, the underlying mechanism remains elusive. We found that induction neuronal-ER stress, which was mostly characterized by an increase phosphorylation a protein kinase R-like ER (PERK) leads to release excess interferon (IFN)β due atypical neuronal-STING signaling pathway. IFNβ enforced polarization primary...
The repair of white matter damage is paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety glial cells ischemic injury, including lineage cells. deficiency knockout mice resulted greater deterioration over 14 d stroke. Consistent with these findings, intranasal delivery nanoparticles stroke improved integrity attenuated long-term...
Abstract The SLC12A cation-Cl − cotransporters (CCC), including NKCC1 and the KCCs, are important determinants of brain ionic homeostasis. SPAK kinase ( STK39 ) is CCC master regulator, which stimulates influx inhibits KCC-mediated efflux via phosphorylation at conserved, shared motifs. Upregulation SPAK-dependent has been implicated in several neurological diseases. Using a scaffold-hybrid strategy, we develop novel potent selective inhibitor,...
Transforming growth factor α (TGF-α) has been reported to play important roles in neurogenesis and angiogenesis the injured brain. The present study characterizes a novel role for TGFα oligodendrocyte lineage cell survival white matter integrity after ischemic stroke. Three days transient (60 min) middle cerebral artery occlusion (tMCAO), expression was significantly increased microglia/macrophages neurons. Expression of receptor TGFα—epidermal (EGFR)—was glial cells ischemia, including...
Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na + /H exchanger-1 (NHE1) reactive astrocytes astrocytic hypertrophy swelling. In this study, we examined role NHE1 protein astrogliosis, demyelination, function a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice...
Recombinant tissue plasminogen activator (tPA) is a Food and Drug Administration-approved thrombolytic treatment for ischemic stroke. tPA also naturally expressed in glial neuronal cells of the brain, where it promotes axon outgrowth synaptic plasticity. However, there are conflicting reports harmful versus neuroprotective effects acute brain injury models. Furthermore, its impact on white matter integrity preclinical traumatic (TBI) has not been thoroughly explored, although disruption...
Abstract Background Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation Na‐K‐Cl cotransport 1 (NKCC1) its upstream kinases WNK (with no lysine) SPAK (the STE20/SPS1‐related proline/alanine‐rich kinase) play a role in astrocytic intracellular Na + overload, hypertrophy, swelling. Therefore, this study, we assessed effect...
Na+ /H+ exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion Nhe1 in Cx3cr1-CreER ;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar corn oil or tamoxifen (Tam)-treated at 48 hr 14 days post-stroke. However, the Tam-treated showed significantly higher survival rate faster neurological function recovery during day 1-14 Deletion prevented elevation CD11b+ /CD45low-med...
Background: Immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is one of the contributing factors for failed immunotherapies. Therefore, there an urgent need to better understand TME and identify novel modulators more effective GBM therapies. We hypothesized that H+ extrusion protein Na/H exchanger 1 (NHE1) plays a role dysregulation glucose metabolism immunosuppression GBM. investigated efficacy blockade NHE1 activity combination with temozolomide (TMZ) therapy increasing...
Differential microglial inflammatory responses play a role in regulation of differentiation and maturation oligodendrocytes (OLs) brain white matter. How microglia-OL crosstalk is altered by traumatic injury (TBI) its impact on axonal myelination neurological function impairment remain poorly understood. In this study, we investigated roles Na+/H+ exchanger (NHE1), an essential pH regulatory protein, proinflammatory activation OL survival murine TBI model induced controlled cortical impact....
Long-term survival of heart transplants is hampered by chronic rejection (CR). Studies indicate the involvement host macrophages in development CR; however, precise role these cells CR unclear. Thus, it important to develop noninvasive techniques serially monitor movement and distribution recipient cardiac allograft vivo.We have employed a rat heterotopic working-heart model for magnetic resonance imaging experiment. Twenty-one (PVG.1U-->PVG.R8) 9 isograft (PVG.R8-->PVG.R8) transplantations...
Cerebral blood flow (CBF) alterations after asphyxial cardiac arrest (CA) are not defined in developmental animal models or humans. We characterized regional and temporal changes CBF from 5 to 150 mins CA of increasing duration (8.5, 9, 12 min) postnatal day (PND) 17 rats using the noninvasive method arterial spin-labeled magnetic resonance imaging (ASL-MRI). also assessed blood-brain barrier (BBB) permeability, evaluated relationship between mean pressure resuscitation. After all durations...
Soluble epoxide hydrolase (sEH) diminishes vasodilatory and neuroprotective effects of epoxyeicosatrienoic acids by hydrolyzing them to inactive dihydroxy metabolites. The primary goals this study were investigate the acute sEH inhibition trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) on infarct volume, functional outcome, changes in cerebral blood flow (CBF) a rat model ischemic stroke. Focal ischemia was induced rats for 90 min followed reperfusion. At end 24 h...
The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters channels. A WNK3-SPAK complex is highly expressed in brain, but its function this organ remains unclear. Here, we investigated the role of brain edema white matter injury after ischemic stroke. Wild-type, WNK3 knockout, SPAK heterozygous or knockout mice underwent transient middle cerebral artery occlusion. One cohort magnetic resonance imaging. Ex-vivo brains...
Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising strategy for treating gliomas, significant barrier is the CD11b
Recent research highlights the function of regulatory T cells (Tregs) in white matter integrity CNS diseases. Approaches that expand number Tregs have been utilized to improve stroke recovery. However, it remains unclear if Treg augmentation preserves early after or promotes repair. This study evaluates effect on injury and repair stroke. Adult male C57/BL6 mice randomly received splenocyte (2 million, iv) transfer 2 h transient (60 min) middle cerebral artery occlusion (tMCAO)....
Macrophages contribute to secondary damage and repair after central nervous system (CNS) injury. Micron-sized paramagnetic iron oxide (MPIO) particles can label macrophages in situ, facilitating three-dimensional (3D) mapping of macrophage accumulation following traumatic brain injury (TBI), via ex vivo magnetic resonance microscopy (MRM) monitoring with imaging (MRI). MPIO were injected intravenously (iv; 4.5 mg Fe/Kg) male C57BL/6J mice (n = 21). A controlled cortical impact (CCI) was...