- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Protein Structure and Dynamics
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Scientific Computing and Data Management
- Pancreatic function and diabetes
- Machine Learning in Bioinformatics
- Diabetes and associated disorders
- Distributed and Parallel Computing Systems
- MicroRNA in disease regulation
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- IL-33, ST2, and ILC Pathways
- HIV Research and Treatment
- Sperm and Testicular Function
- Evolutionary Algorithms and Applications
- Reproductive System and Pregnancy
- Genetic Mapping and Diversity in Plants and Animals
- Reproductive Biology and Fertility
- Advanced Data Storage Technologies
University of Massachusetts Chan Medical School
2015-2025
Vanda Institute
2025
Howard Hughes Medical Institute
2012-2013
Sabancı Üniversitesi
2006-2013
University of Kansas
2010-2013
Stanford University
2013
Offspring affected by sperm small RNAs Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests involvement epigenetic pathways, mechanisms remains unclear. Two studies now show that altered paternal diet affects level mouse sperm. Chen et al. injected transfer RNA (tRNA) fragments from males had been kept on a high-fat into normal oocytes. The progeny displayed disorders and concomitant alteration genes pathways. Sharma observed...
TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological partners remain unknown. Here we identify from cortical neurons by immunoprecipitation followed deep sequencing (RIP-seq). The canonical binding site (TG)n 55.1-fold enriched, moreover, variant adenine in the middle, (TG)nTA(TG)m, highly abundant among reads our RIP-seq library. can be divided...
Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic α- β-cells is crucial for stem cell therapies, islet regeneration strategies, therapies designed to increase β-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods highly purify α-, β-, δ-cells from pancreata by intracellular staining the cell-specific hormone content, sorting subpopulations flow cytometry, and, using next-generation RNA...
Sequencing data has become a standard measure of diverse cellular activities. For example, gene expression is accurately measured by RNA sequencing (RNA-Seq) libraries, protein-DNA interactions are captured chromatin immunoprecipitation (ChIP-Seq), protein-RNA crosslinking (CLIP-Seq) or (RIP-Seq) sequencing, DNA accessibility assay for transposase-accessible (ATAC-Seq), DNase MNase libraries. The processing these techniques involves library-specific approaches. However, in all cases, once...
The transcriptome provides a highly informative molecular phenotype to connect genotype and is most frequently measured by RNA-sequencing (RNA-seq). Therefore, an ultimate goal perturb every gene measure changes in the transcriptome. However, this remains challenging, especially intact organisms due different experimental computational challenges. Here, we present ‘Worm Perturb-Seq (WPS)’, which high-resolution RNA-seq profiles for hundreds of replicate perturbations at time living animal....
Single-cell sequencing technologies have revealed an unexpectedly broad repertoire of cells required to mediate complex functions in multicellular organisms. Despite the multiple roles adipose tissue maintaining systemic metabolic homeostasis, adipocytes are thought be largely homogenous with only 2 major subtypes recognized humans so far. Here we report existence and characteristics 4 distinct human adipocyte subtypes, their respective mesenchymal progenitors. The phenotypes these...
The zebrafish is ideal for studying embryogenesis and increasingly applied to model human disease. In these contexts, RNA-sequencing (RNA-seq) provides mechanistic insights by identifying transcriptome changes between experimental conditions. Application of RNA-seq relies on accurate transcript annotation a genome interest. Here, we find discrepancies in analysis from datasets quantified using Ensembl RefSeq annotations. These issues were due, part, variably annotated 3' untranslated regions...
Type 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T cell–mediated anti-β-cell–specific autoimmunity. To explore the pathogenesis, we interrogated transcriptomes from donors with without type using both bulk-sorted single β-cells. Consistent immunohistological studies, β-cells displayed increased Class I transcripts associated mRNA species. These also expressed for II antigen presentation pathway components, but lacked macrophage marker CD68....
Abstract Background The emergence of high throughput technologies that produce vast amounts genomic data, such as next-generation sequencing (NGS) is transforming biological research. dramatic increase in the volume variety and continuous change data processing tools, algorithms databases make analysis main bottleneck for scientific discovery. datasets typically involves many different computational programs, each which performs a specific step pipeline. Given wide range applications...
Following testicular spermatogenesis, mammalian sperm continue to mature in a long epithelial tube known as the epididymis, which plays key roles remodeling protein, lipid, and RNA composition. To understand for epididymis reproductive biology, we generated single-cell atlas of murine vas deferens. We recovered cell types including principal cells, clear basal along with associated support cells that include fibroblasts, smooth muscle, macrophages other immune cells. Moreover, our data...
Rationale: Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide this process. Therefore, such studies are warranted to address gap. Objective: To identify characterize artery- vein-specific enhancers in the human genome, thereby gaining insights into mechanisms by which blood vessel identity regulated. Methods Results: Using chromatin immunoprecipitation deep sequencing for...
Abstract Summary: Unlike DNA, RNA abundances can vary over several orders of magnitude. Thus, identification RNA–protein binding sites from high-throughput sequencing data presents unique challenges. Although peak in ChIP-Seq has been extensively explored, there are few bioinformatics tools tailored for calling on analogous datasets RNA-binding proteins. Here we describe ASPeak (abundance sensitive detection algorithm), an implementation algorithm that previously applied to detect peaks exon...
Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated investigation of a broad range biological questions. These nucleases also hold tremendous promise for treating variety genetic disorders. In context their therapeutic application, it is important to identify spectrum genomic sequences that are cleaved by candidate when programmed with particular guide RNA, as well cleavage efficiency these sites. Powerful new experimental approaches, such GUIDE-seq,...
Abstract The environment encountered by an organism can modulate epigenetic information in gametes to transmit non-genetically inherited phenotypes offspring. In mouse models, the diet of males regulates specific tRNA-derived RNAs (tDRs) sperm. After fertilization, tDRs regulate embryonic gene expression and generate metabolic adult offspring through uncharacterized changes during development. Here we demonstrate that C. elegans, also accumulate sperm similarly epigenetically We identify...