A5041628493- Wnt/β-catenin signaling in development and cancer
- Liver Disease Diagnosis and Treatment
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Liver physiology and pathology
- Hepatitis B Virus Studies
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Biosimilars and Bioanalytical Methods
- Pancreatitis Pathology and Treatment
- Developmental Biology and Gene Regulation
- Hepatitis C virus research
- Fibroblast Growth Factor Research
- PI3K/AKT/mTOR signaling in cancer
- Advanced Biosensing Techniques and Applications
- Forensic Toxicology and Drug Analysis
- Health and Medical Research Impacts
- Advanced Proteomics Techniques and Applications
- Diet, Metabolism, and Disease
- MRI in cancer diagnosis
- Kruppel-like factors research
Beckman Research Institute
2018-2023
City of Hope
2018-2023
University of Southern California
2011-2021
City Of Hope National Medical Center
2018-2021
Southern California Reproductive Center
2013-2017
Cedars-Sinai Medical Center
2011-2013
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2011
Fred Hutch Cancer Center
2008
We are reporting qualitative and quantitative changes of the extracellular matrix (ECM) associated receptor proteomes, occurring during transition from liver fibrosis steatohepatitis to hepatocellular carcinoma (HCC). compared two mouse models relevant human HCC: PDGFC transgenic (Tg) Pten null mice, disease progression HCC. Using mass spectrometry, we identified in both proteins for 26 collagen-encoding genes, providing first evidence expression at protein level 16 collagens. also...
Background: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras, the detailed molecular mechanisms which effector β-catenin regulates such are largely unknown. We have previously demonstrated that β-catenin’s differential usage of Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous p300 increases self-renewal and...
We report a comprehensive and quantitative analysis of the mouse liver plasma proteomes. The method used is based on extensive fractionation intact proteins, further separation proteins their abundance size, high-accuracy mass spectrometry. This reached depth in proteomic profiling not reported to date for mammalian tissue or biological fluid, with 7099 4727 identified high confidence corresponding plasma, respectively. allowed identification both compartments low-abundance such as...
Abstract The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of virus (HBV) replication. This study investigated effects HBx mutations on HBV transcription and recruitment HBx, histone acetyl-transferase P300 deacetylase 1 (HDAC1) to circularized DNA (which resembles covalently closed circular [cccDNA]). Compared with wild type, majority mutants had lower levels intracellular RNA (44–77% reduction) secretory HBsAg (25–81% reduction), 12 reduction encapsidated (33–64%...
The potential for interfering substances to cause inaccurate laboratory results that may significant adverse effects on patient care is well known. Immunoassays are subject interferences not readily detectable prior analysis, but erroneous results.
Chemiluminescence immunoassay (CIA) is used to detect hepatitis C virus (HCV) antibody status on the basis of signal-to-cutoff (S/Co) ratios. Positive results HCV (anti-HCV) are followed by either recombinant immunoblot assay (RIBA) confirm anti-HCV positivity or reverse transcription (RT)-PCR viremia. We hypothesized that analyzing S/Co ratios, we could determine a strategy reduce unnecessary supplementary testing in our population.CIA was performed screen for anti-HCV, and positive were up...
PPAR-γ is essential for differentiation of hepatic stellate cells (HSC), and its loss due to epigenetic repression by methyl-CpG binding protein 2 (MeCP2) causes HSC myofibroblastic activation mediated in part via Wnt pathway, the key cellular event liver fibrosis. Decreased miR-132 was previously proposed promote MeCP2 translation Ppar-γ activated (aHSC). The present study aimed test this notion better understand mechanisms upregulation aHSC. increased on day 3 7 as become primary culture...
Over 400 million years ago, the evolution of vertebrates gave rise to a life cycle in which organism began live longer particularly as an adult. To accommodate such lifespan, underwent adaptation, developing mechanism for long-lived cellular homeostasis. This adaptation required population relatively quiescent somatic stem cells (SSCs) along with more proliferative differentiated daughter cell population, and was necessary safeguard genetic attributes SSCs were endowed. Intriguingly, cAMP...
Background: The ancient and highly evolutionarily conserved Wnt signaling pathway is critical in nearly all tissues organs for an organism to develop normally from embryo through adult. generally parsed into “canonical” or Wnt-β-catenin-dependent “non-canonical” β-catenin-independent signaling. Even though designating as either canonical noncanonical allows easier conceptual discourse about this pathway, fact non-canonical crosstalk regulates complex nonlinear networks. Objective: In...
Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity insulin resistance in mice fed high fat diet. However, their gender-specific roles pathogenesis non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid deficiency prevents Western diet-induced visceral adiposity females but males, attenuates hyperglycemia, global IR, NASH both genders. In contrast, all metabolic sequela including aggravated by (IkbkbΔhep) male female mice. Gene profiling identifies...
Background: Although cyclic AMP-response element binding protein-binding protein (CBP)/β-catenin signaling is known to promote proliferation and fibrosis in various organ systems, its role the activation of pancreatic stellate cells (PSCs), key effector desmoplasia cancer chronic pancreatitis, largely unknown. Methods: To investigate CBP/β-catenin pathway PSCs, we have treated mouse human PSCs with small molecule specific antagonist ICG-001 examined effects treatment on parameters...
Hepatocellular carcinoma (HCC) ranks worldwide as one of the most lethal cancers. In spite vast existing knowledge about HCC, pathogenesis HCC is not completely understood. Discovery novel genes that contribute to will provide new insights for better understanding and treating HCC. The relatively obscure gene midnolin has been studied over two decades; however, its biological roles are largely unknown. Our study first demonstrate functional significance in HCC/cancer: Midnolin expression...
Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that knockdown suppresses liver cancer cell tumorigenicity and this antitumorigenic effect is associated with modulation lipid metabolism, we hypothesized knockout could potentially protect from nonalcoholic fatty disease (NAFLD) which become most common cause chronic Western world. Accordingly,...
Hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV-associated HCC pathogenesis still unclear. Genetic alterations in cancer-related genes have been linked to many human cancers. Here, we aimed explore genetic selected patients with HCC.Targeted sequencing was used analyze six (PIK3CA, TP53, FAT4, IRF2, HNF4α and ARID1A) eight pairs of tumors their adjacent non-tumor tissues. Sanger sequencing, quantitative PCR,...
Differential usage of Kat3 coactivators, CBP and p300, by β-catenin is a fundamental regulatory mechanism in stem cell maintenance initiation differentiation repair. Based upon our earlier pharmacologic studies, p300 serine 89 (S89) critical for controlling differential coactivator via post-translational phosphorylation stem/progenitor populations, appears to be target number kinase cascades. To further investigate mechanisms signal integration effected this domain, we generated S89A...
Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity known environmental risk factors for PDAC, the contribution of moderate alcohol intake to PDAC remains elusive. In present study, we tested whether a combination or induces development in mice. Control Pdx1 Cre ;LSL- G12D mutant mice were fed Western diet containing high levels cholesterol saturated fat, 3.5% alcohol, lipopolysaccharide 5 mo. addition, treated...
Normal long-term repopulating somatic stem cells (SSCs) preferentially divide asymmetrically, with one daughter cell remaining in the niche and other going on to be a transient amplifying required for generating new tissue homeostatic maintenance repair processes, whereas cancer (CSCs) favor symmetric divisions. We have previously proposed that differential β-catenin modulation of transcriptional activity via selective interaction either Kat3 coactivator CBP or its closely related paralog...
The integration of cellular status with metabolism is critically important and the coupling energy production function highly evolutionarily conserved. This has been demonstrated in stem cell biology, organismal, tissue differentiation immune biology. However, a molecular mechanism delineating how cells coordinate couple transcription as they navigate quiescence, growth, proliferation, migration remains its infancy. extreme N-termini Kat3 coactivator family members, CBP p300, by far least...
Background: Collagen production by activated hepatic stellate cells (HSCs) to encapsulate injury is part of the natural wound-healing response in injured liver. However, persistent activation HSCs can lead pathological fibrogenesis. Such HSC could be mediated norepinephrine (NE), a reaction product dopamine beta-hydroxylase (DBH). Objective: To investigate potential paracrine role NE hepatotoxin thioacetamide (TAA)-induced liver fibrosis. Methods: In TAA-treated mice, fibrotic tissue showed...