A5002870194- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Circular RNAs in diseases
- RNA modifications and cancer
- Proteoglycans and glycosaminoglycans research
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Inflammatory Bowel Disease
- Arsenic contamination and mitigation
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Fibroblast Growth Factor Research
- Coral and Marine Ecosystems Studies
- Renal and related cancers
- Cancer Genomics and Diagnostics
- Digestive system and related health
- Zebrafish Biomedical Research Applications
- Extracellular vesicles in disease
- Advanced biosensing and bioanalysis techniques
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
Cornell University
2017-2024
Amgen (United States)
2023-2024
Ithaca College
2022
New York State College of Veterinary Medicine
2021
University of North Carolina at Chapel Hill
2019
The University of Texas at Austin
2015-2016
Pediatrics and Genetics
2016
Highlights•The small molecule SRI-37330 inhibits TXNIP expression in mouse and human islets•SRI-37330 decreases glucagon secretion action blocks hepatic glucose output•Oral reverses obesity- STZ-induced diabetes steatosis mice•Its antidiabetic effects safety profile make an attractive drug candidateSummaryDiabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency glucose-lowering insulin, persistent alpha gluconeogenic glucagon. Still, no therapies that...
EndoC-βH1 is emerging as a critical human β cell model to study the genetic and environmental etiologies of (dys)function diabetes. Comprehensive knowledge its molecular landscape lacking, yet required, for effective use this model. Here, we report chromosomal (spectral karyotyping), (genotyping), epigenomic (ChIP-seq ATAC-seq), chromatin interaction (Hi-C Pol2 ChIA-PET), transcriptomic (RNA-seq miRNA-seq) maps EndoC-βH1. Analyses these define known (e.g., PDX1 ISL1) putative PCSK1 mir-375)...
Abstract Currently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, global serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by potential therapeutic marker normalizes CHGA levels reverses T1D-induced elevations in circulating proinflammatory...
Type 2 inflammation is associated with epithelial cell responses, including goblet hyperplasia, that promote worm expulsion during intestinal helminth infection. How these responses are regulated remains incompletely understood. Here, we show mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and deficiency only nonhematopoietic cells exhibited enhanced clearance hyperplasia following infection Nippostrongylus brasiliensis. Small stem, goblet, tuft expressed CRTH2. CRTH2-deficient...
Background & AimsThe intestinal barrier comprises a monolayer of specialized epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter permeability genetically susceptible host, resulting chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes each type CD will contribute to an improved understanding pathogenic processes identification cell type–specific therapeutic targets. We...
Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal maturation are less understood. Here, we identify miR-29 family to be strikingly induced during late stages of maturation. Brain is associated with a transient, period de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function restrict CH via its targeting Dnmt3a. Deletion in brain, or knockin mutations preventing specifically...
Aging is a consequence of complex molecular changes, but whether single microRNA (miRNA) can drive aging remains unclear. A miRNA known to be upregulated during both normal and premature miR-29. We find miR-29 also among the top miRNAs predicted aging-related gene expression changes. show that partial loss extends lifespan Zmpste24-/- mice, an established model progeria, indicating functionally important in this accelerated model. To examine alone sufficient promote phenotypes, we generated...
Regulatory T (Treg) cells have long been recognized as modulators of immunological tolerance and homeostasis. Previously, we used scRNA-seq to reveal significant Treg heterogeneity in response IL-2-induced activation. Herein, leveraged enrichment analyses, well bulk single nucleus multi-omics splenic lung Tregs, uncover confirm the importance transcription factors (TFs) chromatin remodeling Multiple bZIP TF motifs showed increased accessibility post IL-2 treatment, with correlated...
The Drosophila oskar (osk) mRNA is unusual in that it has both coding and noncoding functions. As an mRNA, osk encodes a protein required for embryonic patterning germ cell formation. Independent of function, the absence disrupts formation karyosome blocks progression through oogenesis. Here we show loss also affects distribution regulatory proteins, relaxing their association with large RNPs within germline, allowing them to accumulate somatic follicle cells. This other functions are...
Fibrolamellar carcinoma (FLC) is a rare liver cancer that primarily affects adolescents and young adults. It characterized by heterozygous approximately 400-kb deletion on chromosome 19 results in unique fusion between DnaJ heat shock protein family member B1 (DNAJB1) the alpha catalytic subunit of kinase A (PRKACA). The role microRNAs (miRNAs) FLC remains unclear. We identified dysregulated miRNAs investigated whether dysregulation 1 key miRNA contributes to pathogenesis. analyzed small RNA...
MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation certain miRNAs in the liver has been shown to contribute pathogenesis Type 2 diabetes (T2D), part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven (including miR-29b) that consistently aberrantly expressed across five different rodent models metabolic dysfunction share feature resistance (IR). We also showed miR-29b exhibits...
Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Although FLC tumors exhibit distinct gene expression profile, the chromatin regulatory landscape and genes most critical for tumor cell survival remain unclear. Here, we use run-on sequencing to discover ∼7,000 enhancers 141 enhancer hotspots activated in relative nonmalignant liver. Bioinformatic analyses reveal aberrant ERK/MEK signaling candidate master transcriptional...
Abstract Many broadly‐dispersing corals acquire their algal symbionts (Symbiodiniaceae) “horizontally” from environment upon recruitment. Horizontal transmission could promote coral fitness across diverse environments provided that can associate with divergent algae range and these exhibit reduced dispersal potential. Here we quantified community divergence of Cladocopium in two host species ( Acropora hyacinthus, digitifera ) spatial scales (reefs on the same island, between islands)...
Evidence is mounting that composition of microorganisms within a host can play an essential role in total holobiont health. In corals, for instance, studies have identified algal and bacterial taxa significantly influence coral function these communities depend on environmental context. However, few linked genetics to microbial partners across environments single population. Here, using 2b-RAD sequencing corals metabarcoding their associated (ITS2) (16S) communities, we show evidence reef...
Fibrolamellar carcinoma (FLC) is a rare liver cancer that disproportionately affects adolescents and young adults. Currently, no standard of care available there remains dire need for new therapeutics. Most patients harbor the fusion oncogene DNAJB1-PRKACA (DP fusion), but clinical inhibitors are not yet developed it critical to identify downstream mediators FLC pathogenesis. Here, we long noncoding RNA LINC00473 among most highly upregulated genes in tumors determine strongly suppressed by...
Arsenic (As) is a toxic metalloid. Inorganic arsenic (iAs) form of As commonly found in drinking water and some foods. Overwhelming evidence suggests that people chronically exposed to iAs are at risk developing cancer or cardiovascular, neurological, metabolic diseases. Although the mechanisms underlying iAs-associated illness remain poorly characterized, growing body literature raises possibility microRNAs (miRNAs), post-transcriptional gene suppressors, may serve as mediators and/or early...
Trimethylamine-N-oxide (TMAO), a microbial choline metabolism byproduct that is processed in the liver and excreted into circulation, associated with increased atherosclerotic lesion formation cardiovascular disease risk. Genetic regulators of TMAO levels are largely unknown. In present study, we used 288 mice from genetically heterogeneous mouse population [Diversity Outbred (DO)] to determine hepatic microRNA associations context an atherogenic diet. We also validated findings two...
Fibrolamellar carcinoma (FLC) is an aggressive liver cancer primarily afflicting adolescents and young adults. Most patients with FLC harbor a heterozygous deletion on chromosome 19 that leads to the oncogenic gene fusion, DNAJB1-PRKACA. There are currently no effective therapeutics for FLC. To address that, it critical gain deeper mechanistic insight into pathogenesis. We assembled large sample set of nonmalignant tissue (n = 52) performed integrative multiomic analysis. Specifically, we...
Inhalation exposure to ozone (O3) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated in part by changes cellular transcriptional programs. These programs may be regulated microRNAs transferred between cells (e.g., epithelial and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice filtered air (FA), 1, or 2 ppm O3 inhalation collected bronchoalveolar lavage fluid (BALF) 21 h later for...
Abstract Arsenic is a pervasive environmental toxin that listed as the top priority for investigation by Agency Toxic Substance and Disease Registry. While chronic exposure to arsenic associated with type 2 diabetes (T2D), underlying mechanisms are largely unknown. We have recently demonstrated treatment of INS-1 832/13 pancreatic beta cells impairs glucose-stimulated insulin secretion (GSIS), T2D hallmark. also shown alters microRNA profile cells. MicroRNAs well-established...
MicroRNAs (miRNAs) are known regulators of lipid homeostasis. We recently demonstrated that miR-29 controls the levels circulating cholesterol and triglycerides, but mechanisms remained unknown. In present study, we systemic delivery locked nucleic acid inhibitor (LNA29) through subcutaneous injection effectively suppresses hepatic expression dampens de novo lipogenesis (DNL) in liver chow-fed mice. Next, used mice with liver-specific deletion Sirtuin 1 (L-Sirt1 KO), a validated target...
Chronically altered levels of circulating lipids, termed dyslipidemia, is a significant risk factor for number metabolic and cardiovascular morbidities. MicroRNAs (miRNAs) have emerged as important regulators lipid balance, been implicated in proposed candidate therapeutic targets lipid-related disorders including atherosclerosis. A major limitation most murine studies miRNAs that they performed just one (or very few) inbred strains, such C57BL/6. Moreover, although individual associated...