A5000831778- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Single-cell and spatial transcriptomics
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Atherosclerosis and Cardiovascular Diseases
- RNA modifications and cancer
- Nutrition and Health in Aging
- Genetic Associations and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Autism Spectrum Disorder Research
- Bacteriophages and microbial interactions
- Frailty in Older Adults
- Bat Biology and Ecology Studies
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Xenotransplantation and immune response
- Olfactory and Sensory Function Studies
- Animal Genetics and Reproduction
- Chromosomal and Genetic Variations
University of Utah
2015-2025
Harvard University
2010-2021
New York Stem Cell Foundation
2013-2019
University of California, San Diego
2009-2018
GreenLight Biosciences (United States)
2016
Howard Hughes Medical Institute
2010
Institute of Molecular and Cell Biology
2010
Institute of Biomedical Science
2010
Genomic imprinting results in preferential expression of the paternal or maternal allele certain genes. We have performed a genome-wide characterization mouse embryonic and adult brain. This approach uncovered parent-of-origin allelic effects more than 1300 loci. identified parental bias individual genes specific transcript isoforms, with differences between brain regions. Many imprinted are expressed neural systems associated feeding motivated behaviors, biases preferentially target genetic...
Significance We present an unusual mechanism for the well-known association between red meat consumption and carcinoma risk involving nonhuman sialic acid N -glycolylneuraminic (Neu5Gc). first evaluate Neu5Gc content of various foods to show that meats are particularly rich in orally bioavailable then investigate human-like Neu5Gc-deficient mice fed this form Neu5Gc. When such were challenged with anti-Neu5Gc antibodies, they developed evidence systemic inflammation. Long-term exposure...
Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects the adult mouse brain. Our study identified selection of X chromosome glutamatergic neurons female cortex. Moreover, analysis cortex and hypothalamus 347 autosomal genes with features. In hypothalamus, imprinted were mostly found females, which suggests parental influence over hypothalamic...
Significance Highly expressed genes are encoded by codons that correspond to abundant tRNAs, a phenomenon thought ensure high expression levels. An alternative interpretation is highly codon-biased support efficient translation of the rest proteome. Until recently, it was impossible examine these alternatives, since statistical analyses provided correlations but not causal mechanistic explanations. Massive genome engineering now allows recoding and examining effects on cellular physiology...
The nonhuman sialic acid N-glycolylneuraminic (Neu5Gc) is metabolically incorporated into human tissues from certain mammalian-derived foods, and this occurs in the face of an anti-Neu5Gc “xeno-autoantibody” response. Given evidence that process contributes to chronic inflammation some diseases, it important understand when how these antibodies are generated humans. We show here appear during infancy correlate with weaning exposure dietary Neu5Gc. However, Neu5Gc alone cannot elicit mice a...
Genome editing using the CRISPR/Cas9 system requires presence of guide RNAs bound to Cas9 endonuclease as a ribonucleoprotein (RNP) complex in cells, which cleaves host cell genome at sites specified by RNAs. New genetic material may be introduced during repair double-stranded break via homology dependent (HDR) if suitable DNA templates are delivered with CRISPR components. Early methods used plasmid or viral vectors make these components cell, however newer approaches recombinant protein...
Engineering radically altered genetic codes will allow for genomically recoded organisms that have expanded chemical capabilities and are isolated from nature. We previously reassigned the translation function of UAG stop codon; however, reassigning sense codons poses a greater challenge because such more prevalent, their usage regulates gene expression in ways difficult to predict. To assess feasibility altering code, we selected panel 42 highly expressed essential genes modification....
Significance Bacterial recombineering allows researchers to interrogate microbes by modifying their genomic DNA. Improvements the efficiency of have allowed many simultaneous edits be made at once. Here we describe "serial enrichment for efficient recombineering" (SEER), a method identifying single-stranded DNA-annealing proteins (SSAPs) in microbe interest. We use SEER identify two SSAPs: 1) CspRecT doubles editing over Redβ, state-of-the-art Escherichia coli recombineering; and 2) PapRecT...
Genes are typically assumed to express both parental alleles similarly, yet cell lines show random allelic expression (RAE) for many autosomal genes that could shape genetic effects. Thus, understanding RAE in human tissues improve our of phenotypic variation. Here, we develop a methodology perform genome-wide profiling and biallelic GTEx datasets 832 people 54 tissues. We report 2,762 with some properties similar randomly inactivated X-linked genes. found is associated rapidly evolving...
Abstract Heart disease is common in both humans and chimpanzees, manifesting typically as sudden cardiac arrest or progressive heart failure. Surprisingly, although chimpanzees are our closest evolutionary relatives, the major cause of different two species. Histopathology data affected chimpanzee hearts from primate centers, analysis literature indicate that death (and gorillas orangutans) commonly associated with diffuse interstitial myocardial fibrosis unknown cause. In contrast, most...
Although N-acetyl groups are common in nature, N-glycolyl rare. Mammals express two major sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic (Neu5Gc). humans cannot produce Neu5Gc, it is detected the epithelial lining of hollow organs, endothelial vasculature, fetal tissues, carcinomas. This unexpected expression hypothesized to result via metabolic incorporation Neu5Gc from mammalian foods. accumulation has relevance for diseases associated with such nutrients, interaction...
Here, we describe an RNA-sequencing (RNA-seq)-based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which call noncanonical genomic imprinting effects. We profile in arcuate nucleus (ARN) and dorsal raphe of female mouse brain as well skeletal muscle (mesodermal) liver (endodermal). Our study uncovers hundreds autosomal X-linked Noncanonical is highly tissue-specific enriched ARN, but rare liver. These effects are reproducible...
Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos report that Asian elephants have increased neoplasia malignancy prevalence compared with African bush This is consistent observed higher to tuberculosis elephant endotheliotropic herpesvirus (EEHV) in To investigate genetic mechanisms underlying disease resistance, differential responses between among other traits, we sequenced...
Disrupting the interaction between primase and helicase in Escherichia coli increases Okazaki fragment (OF) length due to less frequent primer synthesis. We exploited this feature increase amount of ssDNA at lagging strand replication fork that is available for λ Red-mediated Multiplex Automatable Genome Engineering (MAGE). Supporting concept, we demonstrate MAGE enhancements correlate with OF length. Compared a standard recombineering strain (EcNR2), longest OFs displays on average 62% more...
Significance This work presents the genome-wide replacement of all rare AGR (AGA and AGG) arginine codons in essential genes Escherichia coli with synonymous CGN alternatives. Synonymous codon substitutions can lethally impact noncoding function by disrupting mRNA secondary structure ribosomal binding site-like motifs. Here we quantitatively define range tolerable deviation these metrics use this relationship to provide critical insight into choice recoded genomes. demonstrates that removal...
N-glycolylneuraminic acid (Neu5Gc) is a non-human red-meat-derived sialic immunogenic to humans. Neu5Gc can be metabolically incorporated into glycan chains on human endothelial and epithelial surfaces. This represents the first example of "xeno-autoantigen", against which circulating "xeno-autoantibodies" react. The resulting inflammation ("xenosialitis") has been demonstrated in human-like Neu5Gc-deficient mice contributed carcinoma progression via antibody-mediated inflammation....
The identity of most functional elements in the mammalian genome and phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis patterns accelerated evolution species with highly distinctive traits to discover candidate for clinically important phenotypes. We identify regions (ARs) elephant, hibernating bat, orca, dolphin, naked mole rat, thirteen-lined ground squirrel lineages conserved regions, uncovering ∼33,000 that bind hundreds different regulatory proteins...
Abstract Selection has been invaluable for genetic manipulation, although counter-selection historically exhibited limited robustness and convenience. TolC, an outer membrane pore involved in transmembrane transport E. coli, implemented as a selectable/counter-selectable marker, but escape frequency using colicin E1 precludes tolC inefficient manipulations and/or with large libraries. Here, we leveraged unbiased deep sequencing of 96 independent lineages exhibiting to identify...
Introduction Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify classify CC stage along its continuum early in the disease process challenging but critical for management. Objectives main objective of this study was determine prevalence overall sex race ethnicity among treatment-naïve PDAC cases using...