A5025981389- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cleft Lip and Palate Research
- Mass Spectrometry Techniques and Applications
- Machine Learning in Bioinformatics
- Gene expression and cancer classification
- Craniofacial Disorders and Treatments
- T-cell and B-cell Immunology
- dental development and anomalies
- Systemic Lupus Erythematosus Research
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Congenital Anomalies and Fetal Surgery
- Salivary Gland Disorders and Functions
- Genetic Syndromes and Imprinting
- Molecular Biology Techniques and Applications
- Lymphoma Diagnosis and Treatment
- Sarcoidosis and Beryllium Toxicity Research
- Fractal and DNA sequence analysis
- MRI in cancer diagnosis
- Atomic and Subatomic Physics Research
- Hedgehog Signaling Pathway Studies
- Bioinformatics and Genomic Networks
- IL-33, ST2, and ILC Pathways
Oklahoma Medical Research Foundation
2016-2025
The University of Texas Health Science Center at Houston
2015
University of Southern California
2012-2015
Centrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk
2011
University of Pittsburgh
2005-2011
UPMC Hillman Cancer Center
2007
Core Laboratories (United States)
2007
Carnegie Mellon University
2007
Cleft palate is one of the most common human birth defects and associated with multiple genetic environmental risk factors. Although mutations in genes encoding transforming growth factor beta (TGFβ) signaling molecules interferon regulatory 6 (Irf6) have been identified as factors for cleft palate, little known about relationship between TGFβ IRF6 activity during formation. Here, we show that regulates expression Irf6 fate medial edge epithelium (MEE) palatal fusion mice. Haploinsufficiency...
Molecules involved in WNT/β-catenin signaling show specific spatiotemporal expression and play vital roles myogenesis; however, it is still largely unknown how regulates each step of myogenesis. Here, we that can control diverse biological processes myogenesis by regulating step-specific molecules. In order to identify the temporally molecules muscle development homeostasis, used vitro culture systems for both primary mouse myoblasts C2C12 cells, which differentiate into myofibers. We found...
Abstract Genetic variants can confer risk to complex genetic diseases by modulating gene expression through changes the epigenome. To assess degree which influence epigenome activity, we integrate epigenetic and genotypic data from lupus patient lymphoblastoid cell lines identify that induce allelic imbalance in magnitude of histone post-translational modifications, referred herein as quantitative trait loci (hQTLs). We demonstrate enhancer hQTLs are enriched on autoimmune disease haplotypes...
Disrupted ERK1/2 signaling is associated with several developmental syndromes in humans. To understand the function of Erk2 postmigratory neural crest populating craniofacial region, we studied two mouse models: Wnt1-Cre;Erk2fl/fl and Osr2-Cre;Erk2fl/fl. mice exhibited cleft palate, malformed tongue, micrognathia mandibular asymmetry. Cleft palate these was delay/failure palatal shelf elevation, caused by tongue malposition micrognathia. Osr2-Cre;Erk2fl/fl mice, which deletion restricted to...
Clefting of the soft palate occurs as a congenital defect in humans and adversely affects physiological function palate. However, molecular cellular mechanism clefting remains unclear because few animal models exhibit an isolated cleft Using three-dimensional microCT images histological reconstruction, we found that loss TGFβ signaling palatal epithelium led to muscle defects Tgfbr2fl/fl;K14-Cre mice. Specifically, mass was decreased palates Tgfbr2 mutant mice, following cell proliferation...
CD4+ T cells predominate in salivary gland (SG) inflammatory lesions Sjögren's syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR amplify paired cell receptor α (TCRα) β transcripts single CD4+CD45RA- from SG peripheral blood (PB) 10 individuals with primary SS, 9 whom shared the HLA DR3/DQ2 risk haplotype. TCRα sequences were obtained a median 91 107 PB per...
Biological sex differences in morbidity upon influenza A virus (IAV) infection are linked to stronger IFN-centered immune responses females, yet the regulatory role of hormone receptors cell subsets is incompletely understood. Lung-resident group 2 innate lymphoid cells (ILC2s) express notably high levels androgen (AR). In IAV infection, ILC2s produce type cytokines and facilitate tissue repair, but they also may be functionally suppressed by 1 cytokines. Here we report magnitude lung ILC2...
Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons connective tissues craniofacial region originate neural crest (CNC) cells. Loss transforming growth factor β (TGFβ) type II receptor CNC cells mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due to failure cell-cell communication between mesoderm during development. However, it still unclear how TGFβ signaling regulates...
Current ovarian cancer maintenance therapy is limited by toxicity and no proven impact on overall survival. To study a strategy targeted at missense mutant p53, we hypothesized that the release of p53 from mortalin inhibition SHetA2 drug combined with reactivation PRIMA-1MET inhibits growth tumor establishment synergistically in mutant-p53 dependent manner. The Cancer Genome Atlas (TCGA) data serous tumors were evaluated for TP53 HSPA9/mortalin status. tested cell lines fallopian tube...
Sarcoidosis is a systemic inflammatory disease characterized by infiltration of immune cells into granulomas. Previous gene expression studies using heterogeneous cell mixtures lack insight cell-type-specific dysregulation. We performed the first single-cell RNA-sequencing study sarcoidosis in peripheral 48 patients and controls. Following unbiased clustering, differentially expressed genes were identified for 18 types bioinformatically assessed function pathway enrichment. Our results...
The differentiation of BK virus-associated renal allograft nephropathy (BKVAN) from acute rejection (AR) in transplant recipients is an important clinical problem because the treatment can be diametrically opposite for two conditions. aim this discovery-phase biomarker development study was to examine feasibility developing a noninvasive method differentiate BKVAN AR. Surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry analysis used compare proteomic...
The development of the craniofacial muscles requires reciprocal interactions with surrounding tissues that originate from cranial neural crest cells (CNCCs). However, molecular mechanism involved in tissue-tissue between CNCCs and muscle progenitors during is largely unknown. In current study, we address how regulate tongue other using Wnt1-Cre; Alk5(fl/fl) mice, which loss Alk5 results severely disrupted formation. We found Bmp4 responsible for reduced proliferation myogenic progenitor mice...
We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on SLE autoimmune (AI) disease risk haplotypes modulate regulatory activity allele dependent manner. Our study demonstrates that hQTLs, as group, are more likely MPRA compared other variant classes tested, including set of eQTLs...
The purpose of this study was to provide a univariate and multivariate analysis genomic microbial data salivary mass-spectrometry proteomic profiles for dental caries outcomes. In order determine potential useful biomarkers caries, classification employed build predictive models capable classifying sample with generalization performance. We used high-throughput methodologies including multiplexed arrays SELDI-TOF-MS profiling characterize the oral flora proteome in 204 children aged 1–8...
Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys–Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 cranial neural crest cells (Tgfbr2fl/fl;Wnt1-Cre mice) develop cleft palate as the result abnormal TGFβ signaling activation. However, little is known about metabolic processes downstream during palatogenesis. Here, we show that mutant palatal mesenchymal spontaneously accumulate lipid...
Abstract Nonsyndromic orofacial clefts are common birth defects whose etiology is influenced by complex genetic and environmental factors gene–environment interactions. Although these risk not yet fully elucidated, it known that alterations in transforming growth factor‐beta (TGFβ) signaling can cause craniofacial abnormalities, including cleft palate, mammals. To elucidate the downstream targets of TGFβ palatogenesis, we analyzed gene expression profiles Tgfbr2 fl/fl ;Wnt1‐Cre mouse embryos...
Abstract Motivation: The ‘reproducibility’ of mass spectrometry proteomic profiling has become an intensely controversial topic. mere mention concern over the data generated from any particular platform can lead to anxiety generalizability its results and role in future discovery proteomics. In this study, we examine reproducibility profiles by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF-MS) across multiple data-generation sessions. We analyze problem terms...
TNFAIP3/A20 is a prominent autoimmune disease risk locus that correlated with hypomorphic TNFAIP3 expression and exhibits complex chromatin architecture over 30 predicted enhancers. This study aimed to functionally characterize an enhancer ∼55 kb upstream of the promoter marked by systemic lupus erythematosus (SLE) haplotype index SNP, rs10499197. Allele effects rs10499197, rs58905141, rs9494868 were tested EMSA and/or luciferase reporter assays in immune cell types. Co-immunoprecipitation,...
Genetic variants in the region of tumor necrosis factor-induced protein 3-interacting 1 (TNIP1) are associated with autoimmune disease and reduced TNIP1 gene expression. The aim this study was to define functional genetic mechanisms driving hypomorphic expression imparted by systemic lupus erythematosus-associated H1 risk haplotype.Dual luciferase electrophoretic mobility shift assays were used evaluate allelic effects 11 on enhancer function nuclear binding immune cell line models...
Objective Genetic variants spanning UBE2L3 are associated with increased expression of the ‐encoded E2 ubiquitin‐conjugating enzyme H7 (UbcH7), which facilitates activation proinflammatory NF‐κB signaling and susceptibility to autoimmune diseases. We undertook this study delineate how genetic carried on UBE2L3/YDJC risk haplotype function drive hypermorphic expression. Methods used bioinformatic analyses, electrophoretic mobility shift assays, luciferase reporter assays identify functionally...