Julie Wilhelmy

Stanford University | SU · Department of Biochemistry

Background Genome-Wide Association Studies (GWAS) have produced strong evidence for association of Schizophrenia (SCZ) in the extended Major Histocompatibility Complex (chromosome 6q), including the Human Leukocyte Antigen (HLA) region. It has been reported that structural polymorphisms in the C4 gene can explain the signal in this region, but it h...

Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial...

We present a new approach for the sensitive detection and accurate quantitation of mRNA gene transcripts in single cells. First, the entire population of mRNAs is encoded with molecular barcodes during reverse transcription. After amplification of the gene targets of interest, molecular barcodes are counted by sequencing or scored on a simple hybri...

Significance RNA sequencing (RNA-Seq) is a common tool for measuring relative gene expression levels. However, as an absolute quantitative tool, the data are prone to various distortions due to biases from library preparation. We improve the quantitative aspects of RNA-Seq by barcoding individual cDNA molecules to correct for amplification bias, di...

Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Amino-ace...

Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using...

Human leukocyte antigen (HLA) genes are the most polymorphic in the human genome. They play a pivotal role in the immune response and have been implicated in numerous human pathologies, especially autoimmunity and infectious diseases. Despite their importance, however, they are rarely characterized comprehensively because of the prohibitive cost of...

A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing as well as detection of cod...

Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by comparison with standard bulk isolation...

Allele-specific expression associated SNPs. (0.04 MB XLS)

SNPs tested for association with kidney aging. (0.15 MB XLS)

Common allele-specific expression across studies. (0.02 MB XLS)

SNPs tested for association with expression. (0.13 MB XLS)

Total expression associated SNPs. (0.02 MB XLS)

Author Summary Although family studies have shown that genes play a role in longevity, it has proven difficult to identify the specific genetic variants involved. We developed a sequential transcriptional profiling and eQTL mapping approach to find genes associated with aging in the kidney. First, we used genome-wide transcriptional profiling to de...

A major challenge in molecular biology is interrogating the human transcriptome on a genome wide scale when only a limited amount of biological sample is available for analysis. Current methodologies using microarray technologies for simultaneously monitoring mRNA transcription levels require nanogram amounts of total RNA. To overcome the sample si...

We developed a robust and reproducible methodology to amplify human sequences in parallel for use in downstream multiplexed sequence analyses. We call the methodology SMART (Spacer Multiplex Amplification Reaction), and it is based, in part, on padlock probe technology. As a proof of principle, we used SMART technology to simultaneously amplify 485...

Microarray technology is becoming a powerful tool for diagnostic, therapeutic, and prognostic applications. There is at present no consensus regarding the optimal technique to isolate nucleic acids from blood leukocyte populations for subsequent expression analyses. Current collection and processing techniques pose significant challenges in the cli...

Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in vivo 31P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characteriz...

We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high tempera...

Technologies that enable the isolation of cell subtypes from small samples of complex populations will greatly facilitate the implementation of proteomics and genomics to human diseases. Transcriptome analysis of blood requires the depletion of contaminating erythrocytes. We report an automated microfluidic device to rapidly deplete erythrocytes fr...

In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging...

Age Distribution of Medical and Related Factors Each row shows the presence of a medical or related factor. Age of patients is shown on the y-axis. Only transitional cell carcinoma showed a strong age bias. We have identified over 20 different factors that might potentially confound our study on aging, such as race, blood pressure, diabetes, and ty...

Comparison of Age Regulation of Gene Expression between Kidney and Muscle Tissue in Humans We obtained the muscle dataset from the GEO database (Welle et al. 2003). To compare age regulation in the kidney and muscle, we queried whether the 447 genes identified as age-regulated in the kidney were similarly age-regulated in the muscle. We determined...

Comparison of Age Regulation of Gene Expression between Humans, Flies, and Worms Reveals No Correlation We compared patterns of gene expression in the aging time course data from C. elegans (Lund et al. 2002) and D. melanogaster (Pletcher et al. 2002) to those in the data for the human kidney. We identified orthologous genes using the criterion tha...

Medical Factors Do Not Affect Age Regulation We used regression models to directly test whether our aging studies were affected by seven medical factors: renal cell carcinoma, transitional cell carcinoma, size of tumor, hypertension, systolic blood pressure, diastolic blood pressure, or diabetes mellitus. Scatterplots show age-related slopes using...

Affymetrix HG-U133 Set Gene Chip Protocol (40 KB DOC).

Patients Recruited by Age Group (13 KB XLS).

Age-Related Genes by Location within the Kidney (53 KB XLS).

Medical History of Patients (33 KB XLS).

Age-Related Genes (p < 0.001) Excluding Those with Higher Expression Levels in Blood than in Kidney, Arranged by Fold Change (75 KB XLS).

Age-Related Genes (p < 0.001) Arranged by p-Value (135 KB XLS).

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccha...