A5034086813- Epigenetics and DNA Methylation
- GDF15 and Related Biomarkers
- Nutrition and Health in Aging
- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- Apelin-related biomedical research
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Health, Environment, Cognitive Aging
- Cancer-related gene regulation
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Genetic factors in colorectal cancer
- Circular RNAs in diseases
- Genetic Associations and Epidemiology
- Frailty in Older Adults
Johns Hopkins University
2015-2024
Salk Institute for Biological Studies
2023-2024
University of Southern California
2018-2024
National Human Genome Research Institute
2016-2023
National Institutes of Health
2014-2023
Johns Hopkins Medicine
2023
Southern California University for Professional Studies
2020
National Institute of Diabetes and Digestive and Kidney Diseases
2014
University of Vermont
2011-2012
Recent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular pixel resolution, thereby hindering the identification of cell-type-specific spatial patterns and gene expression variation. To address this challenge, we develop STdeconvolve as a reference-free approach to deconvolve underlying cell types comprising such resolution transcriptomics (ST) datasets. Using simulated well real ST datasets from diverse technologies variety resolutions...
Recent technological advances have enabled spatially resolved measurements of expression profiles for hundreds to thousands genes in fixed tissues at single-cell resolution. However, scalable computational analysis methods able take into consideration the inherent 3D spatial organization cell types and nonuniform cellular densities within are still lacking. To address this, we developed MERINGUE, a framework based on autocorrelation cross-correlation identify with heterogeneous patterns,...
Abstract SARS-CoV-2 induces a muted innate immune response compared to other respiratory viruses. Mitochondrial dynamics might partially mediate this effect of on immunity. Polypeptides encoded by open reading frames SARS-CoV and have been shown localize mitochondria disrupt Antiviral Signaling (MAVS) protein signaling. Therefore, we hypothesized that would distinctly regulate the mitochondrial transcriptome. We analyzed multiple publicly available RNASeq data derived from primary cells,...
‘Normal’ genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination C (U/G) and methyl-C (T/G). Thus, a mutagenic effect their repair could constitute serious genetic burden. We show here while introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking at significantly higher rate than no mismatch controls. Most involved TpC, substrate some single strand-specific APOBEC cytidine...
Advanced age is associated with a decline in cognitive function, likely caused by combination of modifiable and non-modifiable factors such as genetics lifestyle choices. Mounting evidence suggests that humanin other mitochondrial derived peptides play role several age-related conditions including neurodegenerative disease. Here we demonstrate administration has neuroprotective effects vitro human cell culture models sufficient to improve cognition vivo aged mice. Furthermore, cohort, using...
Compared to enhancers, silencers are notably difficult identify and validate experimentally. In search for human silencers, we utilized H3K27me3-DNase I hypersensitive site (DHS) peaks with tissue specificity negatively correlated the expression of nearby genes across 25 diverse cell lines. These regions predicted be since they physically linked, using Hi-C loops, or associated, quantitative trait loci (eQTL) results, a decrease in gene much more frequently than general H3K27me3-DHSs. Also,...
MOTS-c is an exercise mimetic and improves insulin sensitivity in aged diet-induced obese mice. Although plasma markers are good for the metabolic condition, whether changes mice has not been examined. Here, we used unbiased metabolomics approach to examine effect of on dysfunction. We found that three pathways – sphingolipid metabolism, monoacylglycerol dicarboxylate metabolism were reduced MOTS-c–injected Interestingly, these upregulated T2D models. increases beta-oxidation prevent fat...
Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute T2D risk, the functional effects of and therapeutic potential mitochondrial-derived peptides at are underexplored. Here, we showed Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads a K14Q amino acid replacement MOTS-c, insulin sensitizing peptide. Meta-analysis three cohorts (n = 27,527, J-MICC, MEC, TMM) show that males but not...
Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate functional role PD-associated mtSNP that impacts mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, PD risk, within small open reading frame encoding SHLP2. This results in an alternative form SHLP2 (lysine 4 replaced arginine;...
MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing subsequent assays revealed that prevents lipid infiltration in muscle. Since accumulation is one of the common pathologies among other atrophies induced by aging, obesity, cancer cachexia, denervation, could be effective atrophy models as well.
Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin MPI raise an important question concerning contribution epigenetic mechanisms such as DNA methylation to meiosis. Interestingly, previous studies concluded male mice, genome-wide patters are set place prior meiosis remain constant subsequently. However, no examined during systematic manner...
Abstract The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some carriers exhibit resistance AD even in advanced age. Humanin, mitochondrial‐derived peptide comprising 24 amino acids, has variants linked cognitive resilience Our research uncovered unique humanin variant, P3S, specifically enriched centenarians with the allele. Through silico analyses subsequent experimental validation, we demonstrated strong...
The mitochondrial-derived peptides (MDPs) are a novel group of natural occurring that have important signaling functions and biological activity. Both humanin small-humanin-like peptide 2 (SHLP2) been reported to act as insulin sensitizers modulate metabolism. By using metabolomic approach, this study explores how the plasma metabolite profile is regulated in response SHLP2 treatment diet-induced obesity (DIO) mouse model. results also shed light on potential mechanism underlying MDPs'...
Abstract One epigenetic hallmark of many cancer types is differential DNA methylation occurring at multiple loci compared to normal tissue. Detection and assessment the state a specific locus could be an effective diagnostic. We assessed effectiveness hypermethylation CpG island ZNF154 , previously reported multi-cancer signature for use in blood-based detection assay. To predict its effectiveness, we levels 3698 primary tumors encompassing 11 solid cancers, 724 controls, 2711 peripheral...
Abstract Motivation Spatial omics data demand computational analysis but many tools have resource requirements that increase with the number of cells analyzed. This presents scalability challenges as researchers use spatial technologies to profile millions cells. Results To enhance analysis, we developed a rasterization preprocessing framework called SEraster aggregates cellular information into pixels. We apply both real and simulated prior variable gene expression demonstrate such can...