A5082616465- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA modifications and cancer
- CAR-T cell therapy research
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Spaceflight effects on biology
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Cancer therapeutics and mechanisms
- Immune Cell Function and Interaction
- Chromosomal and Genetic Variations
- Circadian rhythm and melatonin
- Developmental Biology and Gene Regulation
- Silicon Carbide Semiconductor Technologies
- Genetics, Bioinformatics, and Biomedical Research
- Innovation and Socioeconomic Development
- DNA Repair Mechanisms
- Trauma Management and Diagnosis
- Biochemical and Molecular Research
- Reproductive Biology and Fertility
California University of Pennsylvania
2025
Vanderbilt University
2018-2024
University of Pennsylvania
2024
National Institute of Diabetes and Digestive and Kidney Diseases
2017-2022
National Institutes of Health
2017-2022
University of Wisconsin–Madison
2014
Significance Stem cells generate tissues, and they can be hijacked in cancer. A fundamental mechanism of stem cell regulation is signaling from their immediate microenvironment, or niche. Although many niches pathways have been identified, much less known about how respond. Here, we report the discovery two key niche effector genes. These genes are activated by Notch signaling, a conserved clinically significant pathway, together essential for state. Surprisingly, neither was previously...
The chromatin-associated protein WDR5 is a promising pharmacological target in cancer, with most drug discovery efforts directed against an arginine-binding cavity called the WIN site. Despite clear expectation that site inhibitors will alter repertoire of interaction partners, their impact on interactome remains unknown. Here, we use quantitative proteomics to delineate how changed by inhibition. We show inhibitor alters dozens proteins, including those linked phosphatidylinositol 3-kinase...
Massively parallel reporter assays (MPRAs) test the capacity of putative gene regulatory elements to drive transcription on a genome-wide scale. Most activity occurs within accessible chromatin, and recently described methods have combined that capture these regions-such as assay for transposase-accessible chromatin using sequencing (ATAC-seq)-with self-transcribing active region (STARR-seq) selectively potential DNA (ATAC-STARR-seq). Here, we report an integrated approach quantifies...
Gene regulatory divergence between species can result from cis-acting local changes to element DNA sequences or global trans-acting the environment. Understanding how these mechanisms drive evolution has been limited by challenges in identifying changes. We present a comprehensive approach directly identify cis- and trans-divergent elements human rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled self-transcribing active region (ATAC-STARR)...
Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function engineered effector cells. CD38 is cells, and although there have studies showing that an inhibitory in how it does so not fully elucidated. In comparison with as PD1, CTLA4, LAG3, TIM3, we found displays more sustained intense expression following acute...
Topoisomerase II alleviates DNA entanglements that are generated during mitotic replication, transcription, and sister chromatid separation. In contrast to mitosis, meiosis has two rounds of chromosome segregation following one round replication. II, chromatids segregate from each other, similar mitosis. Meiosis I, on the other hand, segregates homologs, which requires pairing, synapsis, recombination. The exact role topoisomerase plays is unknown. a screen reexamining Caenorhabditis elegans...
<title>Abstract</title> Adoptively transferred T cells require cytokine stimulation, which is achieved using lymphodepleting chemotherapy with or without administration of exogenous interleukin 2 (IL-2). Lymphodepleting (LDC) associated cytopenias and attendant complications, while high dose IL-2 causes severe infusion toxicity can stimulate undesirable cell populations. To address these challenges, we developed cis-targeted fusion molecules are comprised an mutein attenuated binding to...
Twist transcription factors, members of the basic helix-loop-helix family, play crucial roles in mesoderm development all animals. Humans have two paralogous genes, TWIST1 and TWIST2, mutations each gene been identified specific craniofacial disorders. Here, we describe a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions (p.Glu117Val p.Glu117Gly) at highly conserved glutamic residue located DNA binding domain TWIST1, subjects frontonasal...
Genetic and environmental manipulations, such as dietary restriction, can improve both health span lifespan in a wide range of organisms, including humans. Changes nutrient intake trigger often overlapping metabolic pathways that generate distinct or even opposite outputs depending on several factors, when restriction occurs the lifecycle organism nature changes nutrients. Due to complexity diversity outputs, underlying mechanisms regulating diet-associated pro-longevity are not yet well...
Establishment of DNA methylation (DNAme) patterns is essential for balanced multi-lineage cellular differentiation, but exactly how these drive phenotypes unclear. While > 80% CpG sites are stably methylated, tens thousands discrete loci form hypomethylated regions (HMRs). Because they lack DNAme, HMRs considered transcriptionally permissive, not all actively regulate genes. Unlike promoter HMRs, a subset non-coding cell type-specific and enriched tissue-specific gene regulatory functions....
Epigenetic modifications provide powerful means for transmitting information from parent to progeny. As a maternally inherited genome that encodes essential components of the electron transport chain, mitochondrial (mtDNA) is ideally positioned serve as conduit transgenerational transmission metabolic information. Here, we evidence mtDNA
ABSTRACT Massively parallel reporter assays test the capacity of putative gene regulatory elements to drive transcription on a genome-wide scale. Most activity occurs within accessible chromatin, and recently described methods have combined that capture these regions—such as assay for transposase-accessible chromatin using sequencing (ATAC-seq)—with self-transcribing active region (STARR-seq) selectively potential DNA (ATAC-STARR-seq). Here, we report multi-omic approach quantifies activity,...
ABSTRACT Genetic and environmental manipulations, such as dietary restriction (DR), can improve both health span lifespan in a wide range of organisms, including humans. Changes nutrient intake trigger often overlapping metabolic pathways that generate distinct or even opposite outputs depending on several factors, when DR occurs the lifecycle organism nature changes nutrients. Due to complexity diversity outputs, underlying mechanisms regulating diet-associated pro-longevity are not yet...
Transcriptional enhancers control cell-type specific gene expression in humans and dysfunction can lead to debilitating diseases, including cancer. Identifying bona-fide is difficult due a lack of spatial or sequence constraints. In addition, only small percentage the genome accessible matured cell types; therefore, most are inactive their chromatin context rather than intrinsic properties DNA itself. For this reason, we decided assay regulatory activity exclusively within chromatin. To do...
To investigate the dynamic localization of Topoisomerase II in live C. elegans we have generated a C-terminally GFP-tagged version TOP-2 at endogenous locus. We found that TOP-2::GFP localizes similar pattern to previously published TOP-2::3XFLAG strain and does not disrupt meiotic chromosome segregation functions this enzyme.
SUMMARY Gene regulatory divergence between species can result from cis -acting local changes to element DNA sequences or global trans the environment. Understanding how these mechanisms drive evolution has been limited by challenges in identifying changes. We present a comprehensive approach directly identify cis- and trans- divergent elements human rhesus macaque lymphoblastoid cells using ATAC-STARR-seq. In addition thousands of changes, we discover an unexpected number (~10,000) show that...
ABSTRACT Establishment of DNA methylation (DNAme) patterns is essential for balanced multi-lineage cellular differentiation, but exactly how these drive phenotypes unclear. While >80% CpG sites are stably methylated, tens thousands discrete loci form hypomethylated regions (HMRs). Because they lack DNAme, HMRs considered transcriptionally permissive, not all actively regulate genes. Unlike promoter HMRs, a subset non-coding cell-type specific and enriched tissue gene regulatory functions....
Transcriptional enhancers control cell-type specific gene expression in humans and dysfunction can lead to debilitating diseases, including cancer. Identifying bona-fide is difficult due a lack of spatial or sequence constraints. In addition, only small percentage the genome accessible matured cell types; therefore, most are inactive their chromatin context rather than intrinsic properties DNA itself. For this reason, we decided assay regulatory activity exclusively within chromatin. To do...