A5043444042- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- Immune responses and vaccinations
- Osteoarthritis Treatment and Mechanisms
- Immune cells in cancer
- Estrogen and related hormone effects
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- RNA Research and Splicing
- Adipokines, Inflammation, and Metabolic Diseases
- COVID-19 Impact on Reproduction
- Prostate Cancer Treatment and Research
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Gut microbiota and health
- FOXO transcription factor regulation
- Heat shock proteins research
- Diabetes and associated disorders
Baylor College of Medicine
2016-2025
Dan L Duncan Comprehensive Cancer Center
2021-2024
University of Houston
2014-2017
Université de Caen Normandie
2010
Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier progress. Here, we report proteostasis reprogramming as key convergence point of multiple KRASi-resistance mechanisms. Inactivation oncogenic down-regulated both the heat shock response and inositol-requiring enzyme 1α (IRE1α) branch unfolded protein response, causing severe disturbances. However, IRE1α was selectively reactivated an ER stress–independent manner acquired...
Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A-dependent emphysema. However, whether and how they alter the immune responses lung cancer remains unknown. Here, we show that nCB increased PD-L1
Abstract Loss of protein function is a driving force ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as dominant chaperone in haematopoietic stem and progenitor cells. Depletion PPIA accelerates cell found that proteins with intrinsically disordered regions (IDRs) are frequent substrates. IDRs facilitate interactions other nucleic acids can trigger liquid–liquid phase separation. Over 20% substrates involved the formation supramolecular membrane-less...
As estrogen receptor β-/- (ERβ-/-) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing immunohistochemistry to compare gene expression profiles VP young (2-mo-old) aging (18-mo-old) ERβ-/- their WT littermates. We also treated old with an ERβ-selective agonist evaluated protein expression. The most significant findings were that ERβ down-regulates...
Significance Estrogen receptor β (ERβ) is thought to be the predominant nuclear that regulates estrogen signaling in a wide variety of tissues. In several circumstances, it can oppose effects ERα. Here, we generated novel ERβ exon 3-deleted mouse model (ERβ-Δex3) which first zinc finger DNA binding domain missing but remaining C-terminus part present. We observed mutant male mice were normal females anovulatory. Thus, this work demonstrates most physiological functions do not involve...
Significance Liver X receptors (LXRs) are nuclear vital in controlling lipid and glucose metabolism through direct or indirect mechanisms. Here, we demonstrate for the first time, to our knowledge, that, addition changing activity of classic brown adipose tissue, LXRs, especially LXRβ, able regulate browning white tissue (WAT), activation mitochondria, increased energy expenditure. Deletion LXRs removed their suppressive effect on thyrotropin releasing hormone expression brain, thus...
Significance Lung cancer is the leading cause of death worldwide. squamous cell carcinoma (SCCa) classified as central or peripheral, according to location primary tumor. Peripheral SCCa (PSCCa) becoming common SCCa, but reasons for this increase are unclear. Smoking and chronic lung inflammation recognized risk factors cancer. LXR α,β Dko mice accumulate lipid in their lungs develop M1-macrophage-predominant eventually lesions resembling PSCCa. This mouse model may provide a tool study...
Abstract The rise of life expectancy the human population is accompanied by drastic increases age‐associated diseases, in particular Alzheimer's disease (AD), and underscores need to understand how aging influences AD development. Forkhead box O transcription factor 3 (FoxO3) known mediate longevity downstream insulin/insulin‐like growth signaling across species. However, its function adult brain under physiological pathological conditions less understood. Here, we report a region...
It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure the adaptation leaves scars that will affect their subsequent regeneration. We investigated consequences of inflammation on Lgr5
Estrogen, via estrogen receptor alpha (ERα), exerts several beneficial effects on metabolism and energy homeostasis by controlling size, enzymatic activity hormonal content of adipose tissue. The actions sympathetic ganglia, which are key players in the browning process, less well known. In present study we show that ERβ influences subcutaneous tissue (SAT) its both ganglia SAT itself. A 3-day-treatment with a selective agonist, LY3201, induced 1-year-old obese WT ERα-/- female mice....
Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called "trained immunity." However, the specificity cell types responsible for this response remain poorly defined. We established model of trained immunity in mice Mycobacterium avium infection. scRNA-seq analysis revealed HSPCs activate interferon gamma-response genes heterogeneously primary while rare populations...
Abstract Transcription is regulated through a dynamic interplay of DNA-associated proteins, and the composition gene-regulatory complexes subject to continuous adjustments. Protein alterations include post-translational modifications elimination individual polypeptides. Spatially temporally controlled protein removal is, therefore, essential for gene regulation accounts short half-life many transcription factors. The ubiquitin–proteasome system responsible site- target-specific...
Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in US. Proteasome inhibitors are an essential part several standard drug combinations used to treat this incurable cancer. These drugs interfere with main pathway protein degradation lead accumulation damaged proteins inside cells. Despite promising initial responses, multiple cells eventually become resistant most patients. The biology behind relapsed/refractory is complex poorly understood....
The ubiquitin–proteasome pathway precisely controls the turnover of transcription factors in nucleus, playing an important role maintaining appropriate quantities these regulatory proteins. factor c-MYC is essential for normal development and a critical cancer driver. Despite being highly expressed several tissues malignancies, protein also continuously targeted by pathway, which can either facilitate or inhibit degradation. Deubiquitinating proteases remove ubiquitin chains from target...
Intestinal stem cells (ISC) encounter inflammatory insults in immune mediated gastro-intestinal (GI) diseases. It remains unknown whether, and how, they adapt, if the adaptation leaves scars on ISCs that affects their subsequent regeneration capacity. We investigated consequences of inflammation Lgr5+ISCs well-defined clinically relevant models acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic vivo we found undergo metabolic...
Tissue-intrinsic mechanisms that regulate severity of systemic pathogenic immune-mediated diseases, such as acute graft-versus-host disease (GVHD), remain poorly understood. Following allogeneic hematopoietic stem cell transplantation, autophagy, a cellular stress protective response, is induced in host nonhematopoietic cells. To systematically address the role autophagy various tissues, both specific classical target organs GVHD (intestines, liver, and skin) conventionally not known to be...
Proteasome inhibitors have become the standard of care for multiple myeloma (MM). Blocking protein degradation particularly perturbs homeostasis short-lived polypeptides such as transcription factors and epigenetic regulators. To determine how proteasome directly impact gene regulation, we performed an integrative genomics study in MM cells. We discovered that reduce turnover DNA-associated proteins repress genes necessary proliferation through silencing. Specifically, inhibition results...
Abstract Loss of protein quality is a driving force aging 1 . The accumulation misfolded proteins represents vulnerability for long-lived cells, such as haematopoietic stem cells. How these which have the ability to reconstitute all lineages throughout life 2 , maintain their regenerative potential and avert effects poorly understood. Here, we determined content in progenitor cells identify prevalent chaperones that support proteome integrity. We identified Peptidyl-Prolyl Isomerase A (PPIA...
Abstract Alzheimer’s disease (AD) is a progressive and degenerative brain age one of its strongest risk factors. Aging complex process but it reasonable that delayed aging may lower the AD or postpone pathogenesis. Studies in C. elegans revealed activity DAF-16 required for life span extension many long-lived strains. The mammalian homologs are Forkhead box O (FOXO) transcription FOXO3, members FOXO family, has been identified several studies as susceptibility gene human longevity. I found...