A5061151551- Venous Thromboembolism Diagnosis and Management
- Nanoparticle-Based Drug Delivery
- Lanthanide and Transition Metal Complexes
- Nanoplatforms for cancer theranostics
- Cardiac Imaging and Diagnostics
- Bioactive Compounds and Antitumor Agents
- Cancer therapeutics and mechanisms
- Cardiovascular Disease and Adiposity
- Atherosclerosis and Cardiovascular Diseases
- Cardiac tumors and thrombi
- Cerebrovascular and Carotid Artery Diseases
- Diagnosis and Treatment of Venous Diseases
- MRI in cancer diagnosis
- Electron Spin Resonance Studies
- Central Venous Catheters and Hemodialysis
- Photodynamic Therapy Research Studies
- Peptidase Inhibition and Analysis
- Blood Coagulation and Thrombosis Mechanisms
- Advanced MRI Techniques and Applications
- Hippo pathway signaling and YAP/TAZ
- Antiplatelet Therapy and Cardiovascular Diseases
- Angiogenesis and VEGF in Cancer
- Acute Ischemic Stroke Management
- COVID-19 Clinical Research Studies
- Atrial Fibrillation Management and Outcomes
Masonic Medical Research Laboratory
2021-2024
Medical Research Institute
2024
The University of Texas Southwestern Medical Center
2006-2023
Advanced Imaging Research (United States)
2023
Massachusetts General Hospital
2012-2021
Harvard University
2012-2021
Cardiovascular Research Center
2018-2019
Dana-Farber/Harvard Cancer Center
2016-2017
Center for Systems Biology
2012-2014
Imaging Center
2014
Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe multifunctional micelle (MFM) system that is encoded with lung cancer-targeting peptide (LCP), encapsulated superparamagnetic iron oxide (SPIO) doxorubicin (Doxo) MR therapeutic delivery, respectively. The LCP-encoded MFM showed significantly increased alpha(v)beta(6)-dependent cell targeting in H2009 cells over scrambled...
Abstract Lung cancer is the leading cause of cancer-related deaths with current chemotherapies lacking adequate specificity and efficacy. β-Lapachone (β-lap) a novel anticancer drug that bioactivated by NAD(P)H:quinone oxidoreductase 1, an enzyme found specifically overexpressed in non–small cell lung (NSCLC). Herein, we report nanotherapeutic strategy targets NSCLC tumors two ways: (a) pharmacodynamically through use bioactivatable agent, β-lap, (b) pharmacokinetically using biocompatible...
Abstract Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, existence potential common mechanisms pathogenesis remain obscure. Here we show that VSMC cytoskeleton lead to formation a ternary complex comprising histone deacetylase HDAC9, chromatin-remodeling enzyme BRG1, long...
Magnetic resonance imaging is a powerful clinical technique that allows for noninvasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular cancer has been limited by the lack sensitivity detection accuracy depicting biochemical expression these diseases. Here, we combine an ultrasensitive design superparamagnetic polymeric micelles (SPPM) off-resonance saturation (ORS) method to enhance efficacy tumor...
Mice lacking the GTPase RhoA in cardiomyocytes develop greater pathological hypertrophy but reduced fibrosis with chronic stress to heart.
Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving long-term outcome DVT at risk for PTS therefore require new approaches. Here we investigate effects statins—lipid-lowering agents anti-thrombotic and anti-inflammatory properties—in decreasing thrombus burden wall injury, mediators PTS, in established murine stasis non-stasis chemical-induced venous (N = 282 mice). Treatment mice daily...
Amide proton transfer (APT) imaging is one of the chemical exchange saturation (CEST) methods which images between protons free tissue water and amide groups (−NH) endogenous mobile proteins peptides. Previous work suggested ability APT for characterization tumoral grade in brain tumor. In this study, we tested feasibility in-vivo lung tumor investigated whether method could differentiate types on orthotopic xenografts from two malignant cancer cell lines. The results revealed that feasible...
Accurate detection of recurrent same-site deep vein thrombosis (DVT) is a challenging clinical problem. Because DVT formation and resolution are associated with preponderance inflammatory cells, we investigated whether noninvasive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging could identify inflamed, recently formed thrombi thereby improve the diagnosis DVT.We established stasis-induced model in murine jugular veins also novel stasis mice. C57BL/6 mice (n=35)...
Loss-of-function mutations in genes encoding contractile proteins have been observed thoracic aortic aneurysms (TAA). To gain insight into the contribution of protein deficiency pathogenesis TAA, we examined human aneurysm samples. We found multiple gene products deficient TAA samples, and particular, expression SM22α was inversely correlated with size. SM22α-deficient mice demonstrated pregnancy-induced dissection, worsened Fbn1C1039G/+ (Marfan) mice, validating this product as a effector....
Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, impaired quality life. Although catheter-based interventions enabling restoration blood flow (RBF) have demonstrated little benefit on syndrome, impact acuity thrombus mechanisms underlying this finding remain obscure. In experimental clinical studies, we examined whether RBF has a restricted time window for...
To encapsulate 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), a photosensitizer, into polymeric micelles; characterize the and test in vitro photodynamic therapy efficacy against human head neck cancer cells.A nanoparticle design, fabrication, testing study.Polymer chemistry laboratory.Micelles encapsulating mTHPP were produced, micellar size was measured. Ultraviolet visible spectra fluorescence spectroscopy used to mTHPP-loaded micelles. In cell culture using HSC-3 HN-5 cells...
Venous thromboembolism is a major cause of death during and immediately post-sepsis. thrombosis (VT) mediated by cell adhesion molecules leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, secondarily the role VT TLR4, ICAM-1 neutrophils (PMNs). Wild-type (WT), ICAM-1-/-...
Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. This study hypothesized that DCBs could lessen inflammation and plaque progression. Using 25 rabbits with cholesterol feeding- balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon insertion without inflation) was investigated using serial intravascular near-infrared fluorescence−optical coherence tomography ultrasound. In...
Nanoparticulate imaging probes have become an increasingly important arsenal in the visualization of molecular markers for early diagnosis and post-therapy assessment diseases. Surface functionalization these nanoparticles has led to development a variety targeted nanoprobes various modalities (e.g. PET, MRI, optical). Despite advances, detailed understanding nanoparticle targeting kinetics, particularly at time points immediately after injection, is still lacking. In this study, we report...
Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2 integrated fluorescence molecular-structural imaging strategies to quantify DVT-related architecture assess the effect on subsequent DVT resolution vivo.
Patients with heterozygous missense mutations in the ACTA2 or MYH11 gene are known to exhibit thoracic aortic aneurysm and a risk of early-onset dissection. However, less common phenotypes involving arterial obstruction also observed, including coronary cerebrovascular stenotic disease. Herein we implicate HDAC9 complex transcriptional silencing contractile protein-associated genes, undergo downregulation lesions. Furthermore, neointimal formation was inhibited HDAC9- MALAT1-deficient mice...
Using transcriptional profiling of platelets from patients presenting with acute myocardial infarction, we identified myeloid-related protein-14 (MRP-14, also known as S100A9) an infarction gene and reported that platelet MRP-14 binding to CD36 regulates arterial thrombosis. However, whether plays a role in venous thrombosis is unknown. We subjected WT Mrp-14-deficient (Mrp-14-/-) mice experimental models deep vein (DVT) by stasis ligation or partial flow restriction (stenosis) the inferior...
Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge available regarding in vivo mechanisms that govern fibrinolytic efficacy.In particular, it unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target blood-based agents.Utilizing high-resolution optical molecular imaging FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated interrelationships accessibility to age,...