A5089191106- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Peroxisome Proliferator-Activated Receptors
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- Electron Spin Resonance Studies
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Advanced MRI Techniques and Applications
- Pancreatic function and diabetes
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- CAR-T cell therapy research
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Immune cells in cancer
- Liver physiology and pathology
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
University of Illinois Chicago
2016-2024
HEM Technologies (United States)
2023
Jesse Brown VA Medical Center
2019-2020
University of Illinois Hospital & Health Sciences System
2020
Loyola University Chicago
2013-2015
University of Hyderabad
2013-2015
Institute of Life Sciences
2013-2015
Loyola University Medical Center
2014
Northwestern University
2004-2013
Midwestern University
2009
Peroxisome proliferator-activated receptor (PPAR)alpha, beta (also known as delta), and gamma function sensors for fatty acids acid derivatives control important metabolic pathways involved in the maintenance of energy balance. PPARs also regulate other diverse biological processes such development, differentiation, inflammation, neoplasia. In nucleus, exist heterodimers with retinoid X receptor-alpha bound to DNA corepressor molecules. Upon ligand activation, undergo conformational changes...
Abstract Pancreatic ductal adenocarcinoma (PDAC) remains remarkably lethal with a 5-year survival rate of 8%. This is mainly attributed to the late stage presentation, as well widespread resistance conventional therapy. In addition, PDAC tumors are largely nonimmunogenic, and most patients have displayed incomplete responses cancer immunotherapies. Our group has previously identified TGFβ crucial repressor antitumor immune function in PDAC, particularly respect cytotoxic T lymphocytes....
Obesity, a major health concern, results from an imbalance between energy intake and expenditure. Leptin-deficient ob/ob mice are paradigmatic of obesity, resulting excess storage. Mice lacking acyl-CoA oxidase 1 (Acox1), the first enzyme peroxisomal fatty acid β-oxidation system, characterized by increased expenditure lean body phenotype caused sustained activation peroxisome proliferator-activated receptor α (PPARα) endogenous ligands in liver that remain unmetabolized absence Acox1. We...
Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A), a member of novel family proapoptotic proteins, is expressed abundantly in the brown adipose tissue mouse. Although mRNA not detectable mouse liver, we now show that peroxisome proliferator-activated receptor (PPAR) alpha ligands Wy-14,643 and ciprofibrate increase level PPARalpha-dependent manner, whereas induction liver by PPARgamma overexpression PPARalpha independent. Increase content did alter expression...
Disruption of the peroxisomal acyl-CoA oxidase 1 (Acox1) gene in mouse results development severe microvesicular hepatic steatosis and sustained activation peroxisome proliferator-activated receptor-α (PPARα). These mice manifest spontaneous massive proliferation regenerating hepatocytes eventually develop hepatocellular carcinomas. Human ACOX1, first rate-limiting enzyme β-oxidation pathway, has two isoforms including ACOX1a ACOX1b, transcribed from a single gene. As shows reduced activity...
Abstract The incidence and mortality of hepatocellular carcinoma (HCC) are on a rise in the Western countries including US, attributed mostly to late detection. Sorafenib has been first-line FDA-approved drug for advanced unresectable HCC almost decade, but with limited efficacy due development resistance. More recently, several other multi-kinase inhibitors (lenvatinib, cabozantinib, regorafenib), human monoclonal antibody (ramucirumab), immune checkpoint (nivolumab, pembrolizumab) have...
Abstract The use of oxygen by cells is an essential aspect cell metabolism and a reliable indicator viable functional cells. Here, we report partial pressure (pO 2 ) mapping live as metabolically active For pO imaging, utilized trityl OX071-based pulse electron paramagnetic resonance imaging (EPROI), in combination with 25 mT EPROI instrument, JIVA-25™, that provides 3D maps high spatial, temporal, resolution. To perform environment-controlled apparatus, developed novel multi-well-plate...
Abstract Purpose The determination of blood–brain barrier (BBB) integrity and partial pressure oxygen (pO 2 ) in the brain is substantial interest several neurological applications. This study aimed to assess feasibility using trityl OX071‐based pulse electron paramagnetic resonance imaging (pEPRI) provide a quantitative estimate BBB pO maps mouse brains as function neuroinflammatory disease progression. Methods Five Connexin‐32 (Cx32)–knockout (KO) mice were injected with lipopolysaccharide...
Abstract Purpose Solid crystalline spin probes, such as lithium phthalocyanine (LiPc) and octa‐n‐butoxynaphthalocyanine (LiNc‐BuO), allow repeated oxygen measurement using electron paramagnetic resonance (EPR). Due to their short relaxation times, use for pulse EPR imaging is limited. In this study, we developed tested a new class of solid composite probes that modified the rates R 1 2 LiPc or LiNc‐BuO which allowed pO measurements in full dynamic (0–760 torr) range. Methods The were by...
Abstract Purpose Trityl OXO71‐based pulse electron paramagnetic resonance imaging (EPRI) is an excellent technique to obtain partial pressure of oxygen (pO 2 ) maps in tissues. In this study, we used deep learning techniques denoise 3D EPR amplitude and pO maps. Methods All experiments were performed using a 25 mT imager, JIVA‐25®. The MONAI implementation four neural networks (autoencoder, Attention UNet, UNETR, UNet) was tested, the best model (UNet) then enhanced with joint bilateral...
Peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor, when overexpressed in liver stimulates the induction of adipocyte-specific and lipogenesis-related genes causes hepatic steatosis. We report here that Mediator 1 (MED1; also known as PBP or TRAP220), key subunit complex, is required for high-fat diet-induced steatosis well PPARγ-stimulated adipogenic forms bridge between transcriptional activators RNA polymerase II. MED1 interacts with receptors such PPARγ other...
Lipid droplet proteins (LDPs) coat the surface of triglyceride-rich lipid droplets and regulate their formation lipolysis. We profiled hepatic LDP expression in fatty liver dystrophic (fld) mice, a unique model neonatal steatosis that predictably resolves between postnatal day 14 (P14) P17. Western blotting revealed perilipin-2/ADRP perilipin-5/OXPAT were markedly increased steatotic fld but returned to normal by However, changes perilipin-2 perilipin-5 protein content mice exaggerated...
Abstract Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing beta cells. Bioartificial pancreas (BAP) or cell replacement strategies have shown promise in curing T1D and providing long-term insulin independence. Hypoxia (low oxygen concentration) may occur BAP devices due consumption at early stages after implantation damages cells, addition imposing limitations device dimensions when translating promising results from rodents humans. Finding ways...
Glucocorticoid receptor (GR) agonist dexamethasone (Dex) induces hepatic steatosis and enhances constitutive androstane (CAR) expression in the liver. CAR is known to worsen injury nonalcoholic steatosis. Because transcription coactivator MED1/PPARBP gene required for GR- CAR-mediated transcriptional activation, we hypothesized that disruption of liver cells would result attenuation Dex-induced Here show liver-specific MED1 (MED1(delta Liv)) improves steatotic phenotype In wild-type mice Dex...
Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component the polymerase II mediated gene transcription. Germline deletion Mediator subunit 1 (Med1) in mice results mid-gestational embryonic lethality with developmental impairment multiple organs including heart. Here we show that cardiomyocyte-specific Med1 (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl to α-MyHC-Cre transgenic within 10...
Significance Although activation of PI3K p110α appears to promote pancreatic cancer development via canonical AKT signaling, in the setting a high-fat diet (enriched ω−6 fatty acids), unopposed p110γ inhibition poses risk for severe hepatic damage. Considering that obesity is factor cancer, these observations suggest need caution when translating drugs targeting clinic.
Mixed lineage kinase 3 (MLK3), also known as MAP3K11, was initially identified in a megakaryocytic cell line and is an emerging therapeutic target cancer, yet its role immune cells not known. Here, we report that loss or pharmacological inhibition of MLK3 promotes activation cytotoxicity T cells. abundantly expressed cells, alters serum chemokines, cytokines, CD28 protein expression on subsets. induces vitro, ex vivo, vivo conditions, irrespective activating agents. Conversely,...