A5079452861- Muscle Physiology and Disorders
- Cancer-related molecular mechanisms research
- Computational Drug Discovery Methods
- Grit, Self-Efficacy, and Motivation
- Synthesis and biological activity
- RNA Research and Splicing
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Retinal Diseases and Treatments
- Genetic Neurodegenerative Diseases
- Career Development and Diversity
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Protein Kinase Regulation and GTPase Signaling
- Enzyme Structure and Function
- Advanced Proteomics Techniques and Applications
- Healthcare Education and Workforce Issues
- Retinal Development and Disorders
- Circular RNAs in diseases
- Nutrition and Health in Aging
- Melanoma and MAPK Pathways
- interferon and immune responses
- Genetics, Aging, and Longevity in Model Organisms
- Biotin and Related Studies
- Engineering Education and Pedagogy
University of Iowa
2004-2025
Mayo Clinic in Arizona
2021-2025
Mayo Clinic
2022-2024
National Institutes of Health
2023-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2023-2024
Wichita State University
2021-2023
Eternity Bioscience (United States)
2022
WinnMed
2022
Goethe University Frankfurt
2017
University of Tennessee Health Science Center
2013
The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important lncRNAs.Epigenetically controlled lncRNAs in human umbilical vein were searched exon-array analysis after knockdown histone demethylase JARID1B. Molecular mechanisms investigated RNA pulldown immunoprecipitation, mass spectrometry, microarray, several approaches, CRISPR-Cas9, assay for...
The function of Type 1, classic cadherins depends on their association with the actin cytoskeleton, a connection mediated by alpha- and beta-catenin. phosphorylation state beta-catenin is crucial for its cadherin thus cytoskeleton. We now show that regulated combined activities tyrosine kinase Fer phosphatase PTP1B. phosphorylates PTP1B at 152, regulating binding to continuous dephosphorylation 654. interacts indirectly, through p120ctn. have mapped interaction domains p120ctn peptides...
The worldwide impact of the ongoing COVID-19 pandemic on public health has made imperative discovery and development direct-acting antivirals aimed at targeting viral and/or host targets. SARS-CoV-2 3C-like protease (3CLpro) emerged as a validated target for therapeutics because pivotal role it plays in replication. We describe herein structure-guided design highly potent inhibitors 3CLpro that incorporate their structure novel spirocyclic elements optimizing potency by accessing new...
Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation the adaptive immune responses against tumor. The first-generation STING agonists, cyclic di-nucleotide (CDN), mimicked endogenous ligand guanosine monophosphate adenosine monophosphate, displayed limited clinical efficacy. Here we report discovery SHR1032, a novel small molecule non-CDN agonist. Compared to CDN agonist ADU-S100, SHR1032...
Abstract Aging slowly erodes skeletal muscle strength and mass, eventually leading to profound functional deficits atrophy. The molecular mechanisms of aging are not well understood. To better understand aging, we investigated the potential role ATF4, a transcription regulatory protein that can rapidly promote atrophy in young animals deprived adequate nutrition or activity. test hypothesis ATF4 may be involved studied fed active muscle-specific knockout mice (ATF4 mKO mice) at 6 months age,...
The Myb proto-oncogene encodes the transcription factor c-MYB, which is critical for hematopoiesis. Distant enhancers of form a hub interactions with promoter. We identified long non-coding RNA (Myrlin) originating from -81-kb murine enhancer. Myrlin and are coordinately regulated during erythroid differentiation. TSS deletion using CRISPR-Cas9 reduced expression LDB1 complex occupancy at enhancers, compromising enhancer contacts reducing Pol II in locus. In contrast, CRISPRi silencing left...
Abstract Sarcopenia increases the risk of frailty, morbidity, and mortality in older adults. Resistance exercise training improves muscle size function; however, response to is variable The objective our study was determine both age-independent age-dependent changes transcriptome following progressive resistance training. Skeletal biopsies were obtained before after 12 weeks 8 young (24 ± 3.3 years) 10 (72 4.9 men. RNA extracted from each biopsy prepared for analysis via sequencing. We...
The COVID-19 pandemic is having a major impact on public health worldwide, and there an urgent need for the creation of armamentarium effective therapeutics, including vaccines, biologics, small-molecule to combat SARS-CoV-2 emerging variants. Inspection virus life cycle reveals multiple viral- host-based choke points that can be exploited virus. 3C-like protease (3CLpro), enzyme essential viral replication, attractive target therapeutic intervention, design inhibitors may lead emergence...
A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, inflammatory bowel disease). Thus, TYK2 represents an attractive target develop small-molecule therapeutics for treatment cytokine-driven diseases. Selective inhibition over other JAK isoforms critical achieve a...
We hypothesized that loss of insulin-like growth factor binding protein 3 (IGFBP-3) signaling would produce neuronal changes in the retina similar to early diabetes.To understand better role IGFBP-3 retina, knockout (KO) mice were evaluated for neuronal, vascular, and functional compared wild-type littermates. also cultured retinal endothelial cells (REC) normoglycemia or hyperglycemia determine interaction between TNF-α, as data indicate both proteins are regulated by β-adrenergic receptors...
Abstract The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis age‐related crucial for developing strategies combat this debilitating condition. Long noncoding RNAs (lncRNAs) are largely uncharacterized class biomolecules that have been implicated cellular homeostasis and dysfunction across many tissues cell types. To identify lncRNAs might contribute aging, we screened whose expression...
A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect diverse cells make up CTCs. CTC-derived nucleases are one category proteins could be exploited to meet this challenge. Advantages as CTC biomarkers include: (1) their elevated expression in many cancer cells, including implicated metastasis have undergone epithelial-to-mesenchymal transition; (2) enzymatic activity, which can signal amplification detection...
Aging and many illnesses injuries impair skeletal muscle mass function, but the molecular mechanisms are not well understood. To better understand mechanisms, we generated studied transgenic mice with muscle-specific expression of growth arrest DNA damage inducible α (GADD45A), a signaling protein whose in rises during aging wide range injuries. We found that GADD45A induced several cellular changes characteristic atrophy, including reduction mitochondria oxidative capacity, selective...
In spite of its central role in biology and disease, protein turnover is a largely understudied aspect most proteomic studies due to the complexity computational workflows that analyze vivo rates. To address this need, we developed new tool, TurnoveR, accurately calculate rates from mass spectrometric analysis metabolic labeling experiments Skyline, free open-source proteomics software platform. TurnoveR straightforward graphical interface enables seamless integration into traditional...
SUMMARY The Myb proto-oncogene encodes the transcription factor c-MYB, which is critical for hematopoiesis. Distant enhancers of form a hub interactions with promoter. We identified long non-coding RNA ( Myrlin ) originating from −81 kb murine enhancer. and are coordinately regulated during erythroid differentiation. TSS deletion using CRISPR/Cas9 reduced expression LDB1 complex occupancy at enhancers, compromising enhancer contacts reducing Pol II in locus. In contrast, CRISPRi silencing...