- Alzheimer's disease research and treatments
- Cancer Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- Computational Drug Discovery Methods
- Advanced MRI Techniques and Applications
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- Liver Disease Diagnosis and Treatment
- Pancreatitis Pathology and Treatment
- Medical Imaging Techniques and Applications
- MRI in cancer diagnosis
- Renal and related cancers
- Renal cell carcinoma treatment
- Pancreatic and Hepatic Oncology Research
- Chemical Reactions and Isotopes
- Neurological Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Cancer-related Molecular Pathways
- Cardiac Imaging and Diagnostics
- Mitochondrial Function and Pathology
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Click Chemistry and Applications
- Bioinformatics and Genomic Networks
Indiana University – Purdue University Indianapolis
2015-2024
Indiana University School of Medicine
2015-2024
Texas Children's Hospital
2024
The University of Texas at Austin
2024
Sinai Hospital
2024
Canadian Apheresis Group
2024
Neurosciences Institute
2020-2024
Indiana University
2014-2023
University School
2020-2023
Indiana University Indianapolis
2023
Ca(2+) has been postulated as a cytosolic second messenger in the regulation of cardiac oxidative phosphorylation. This hypothesis draws support from well-known effects on muscle activity, which is stimulated parallel with Ca(2+)-sensitive dehydrogenases (CaDH). The phosphorylation were further investigated isolated porcine heart mitochondria at level metabolic driving force (NADH or Deltapsi) and ATP production rates (flow). resulting force-flow (F-F) relationships permitted analysis...
The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization the model(s) being used. There are numerous that have been generated study Alzheimer's disease (AD) and underlying pathogenesis disease. While transgenic instrumental understanding AD mechanisms risk factors, they limited degree characteristics displayed comparison with humans, full spectrum effects has yet be recapitulated a single mouse model. Model...
The purinergic receptor subtype 7 (P2X7R) represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, potent P2X7R antagonist, has high affinity, blood–brain barrier penetration, and the ability to be radiolabeled with <sup>11</sup>C. We report initial physical biologic characterization of this ligand. <b>Methods:</b><sup>11</sup>C-GSK1482160 was synthesized according published methods. Cell density studies were performed on human embryonic kidney cell lines...
Abstract Alzheimer's disease (AD) is a major cause of dementia, disability, and death in the elderly. Despite recent advances our understanding basic biological mechanisms underlying AD, we do not know how to prevent it, nor have an approved disease‐modifying intervention. Both are essential slow or stop growth dementia prevalence. While current animal models AD provided novel insights into mechanisms, thus far, they been successfully used predict effectiveness therapies that moved clinical...
Abstract Over 5 million Americans and 50 individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated AD currently has no cure. Although clinical trials in patients ultimately required to find safe effective drugs, animal models of permit the integration brain pathologies learning memory deficits that first step developing these new drugs. purpose Association Business Consortium Think Tank meeting was address unmet need improve discovery successful...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a clinically challenging disease with limited treatment options. Despite small percentage of cases defective mismatch DNA repair (dMMR), PDA included in the most immune‐resistant cancer types that are poorly responsive to immune checkpoint blockade (ICB) therapy. To facilitate drug discovery combating this immunosuppressive tumor type, high‐throughput screen platform established newly developed T cell‐incorporated pancreatic organoid model....
Parallel activation of heart mitochondria NADH and ATP production by Ca2+ has been shown to involve the Ca2+-sensitive dehydrogenases F0F1-ATPase. In current study we hypothesize that response time Ca2+-activated is rapid enough support step changes in myocardial workload (∼100 ms). To test this hypothesis, kinetics ofmV˙ O2, [NADH], light scattering were evaluated isolated porcine at 37 °C using a variety optical techniques. The addition was associated with an initial (IRT) O2...
Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder resulting from germline mutations in the NF2 gene. Bilateral vestibular schwannomas, tumors on cranial nerve VIII, are pathognomonic for disease. Furthermore, schwannomas also commonly develop other nerves, dorsal root ganglia and peripheral nerves. These a major cause of morbidity mortality, medical therapies to treat them limited. Animal models that accurately recapitulate full anatomical spectrum human NF2-related...
Traumatic brain injury induces acute lung that negatively impacts the physiology of donor before and after transplantation.
Adipose-derived stromal/stem cells (ASCs) ameliorate hyperglycemia in rodent models of islet transplantation and autoimmune diabetes, yet the precise human ASC (hASC)-derived factors responsible for these effects remain largely unexplored. Here, we show that systemic administration hASCs improved glucose tolerance, preserved β cell mass, increased proliferation streptozotocin-treated nonobese diabetic/severe combined immunodeficient mice. Coculture experiments combining mouse or islets with...
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represents a major hurdle in improving the management of clear cell renal carcinoma (ccRCC). Recent reports suggest that drug is driven by tumor adaptation via epigenetic mechanisms activate alternative survival pathways. The histone methyl transferase EZH2 frequently altered many cancers, including ccRCC. To evaluate its role ccRCC RTKi, we established characterized spontaneously metastatic, patient-derived...
The purpose of this study was to determine if extracellular volume fraction and T1 mapping can be used diagnose chronic pancreatitis (CP).This HIPAA-compliant analyzed 143 consecutive patients with without CP who underwent MR imaging between May 2016 February 2017. Patients were selected for the according inclusion exclusion criteria that considered history clinical laboratory findings. Eligible (n = 119) grouped as normal 60) or mild 22), moderate 27), severe 10) on basis MRCP findings...
Objective The aim of this study was to determine the association pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus. Methods Patients (n = 118) were retrospectively identified categorized into no CP 60), mild 21), moderate 27), severe 10) groups based on clinical history magnetic resonance cholangiopancreatography using Cambridge classification as diagnostic standard. Visceral subcutaneous compartments manually segmented, fat tissue quantitatively...
Late-onset Alzheimer’s disease (AD; LOAD) is the most common human neurodegenerative disease, however, availability and efficacy of disease-modifying interventions severely lacking. Despite exceptional efforts to understand progression via legacy amyloidogenic transgene mouse models, focus on translation with innovative strains that better model complexity AD required accelerate development future treatment modalities. LOAD within population a polygenic environmentally influenced many risk...
Abstract INTRODUCTION MODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory progression of late‐onset disease (LOAD) more accurately. METHODS We created LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, humanized amyloid‐beta (Aβ). Mice were subjected a control diet or high‐fat/high‐sugar (LOAD2+HFD). assessed...
Hydrocephalus is a serious condition that impacts patients of all ages. The standards care are surgical options to divert, or inhibit production of, cerebrospinal fluid; date, there no effective pharmaceutical treatments, our knowledge. causes vary widely, but one commonality this aberrations in salt and fluid balance. We have used genetic model hydrocephalus show ventriculomegaly can be alleviated by inhibition the transient receptor potential vanilloid 4, channel activated changes osmotic...
The 5xFAD mouse is a popular model of familial Alzheimer's disease (AD) that characterized by early beta-amyloid (Aβ) deposition and cognitive decrements. Despite numerous studies, the has not been comprehensively phenotyped for vascular metabolic perturbations over its lifespan.Male female wild type (WT) littermates underwent in vivo18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at 4, 6, 12 months age to assess regional glucose metabolism. A separate cohort mice (4,...