A5024441435- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Plant Molecular Biology Research
- Cancer Genomics and Diagnostics
- Renal Transplantation Outcomes and Treatments
- Cancer Cells and Metastasis
- Immunodeficiency and Autoimmune Disorders
- Metabolism and Genetic Disorders
- Plant Reproductive Biology
- Hematopoietic Stem Cell Transplantation
- Genomics and Phylogenetic Studies
- Plant nutrient uptake and metabolism
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- RNA regulation and disease
- Microtubule and mitosis dynamics
- Genetic Associations and Epidemiology
- Genetic Mapping and Diversity in Plants and Animals
- Gene expression and cancer classification
- Mesenchymal stem cell research
- Immune Response and Inflammation
- BRCA gene mutations in cancer
- Organ Transplantation Techniques and Outcomes
- Cancer, Hypoxia, and Metabolism
Stanford University
2010-2020
Immucor (United States)
2016-2020
Palo Alto University
2015
New York Genome Center
2008-2012
University of Florida
2005
University of Alabama
1993-2002
Carnegie Mellon University
1993
University of Wisconsin–Madison
1993
Human leukocyte antigen (HLA) genes are the most polymorphic in human genome. They play a pivotal role immune response and have been implicated numerous pathologies, especially autoimmunity infectious diseases. Despite their importance, however, they rarely characterized comprehensively because of prohibitive cost standard technologies technical challenges accurately discriminating between these highly related many allelles. Here we demonstrate high-resolution, cost-effective methodology to...
Abstract Several quantitative trait loci (QTL) mapping strategies can successfully identify major-effect loci, but often have poor success detecting with minor effects, potentially due to the confounding effects of major epistasis, and limited sample sizes. To overcome such difficulties, we used a targeted backcross strategy that genetically eliminated effect previously identified QTL underlying high-temperature growth (Htg) in yeast. This facilitated three novel contributing Htg clinically...
Therapeutic decisions in cancer are generally guided by molecular biomarkers or, for some newer therapeutics, primary tumor genotype. However, because or genotypes may change as new metastases emerge, circulating cells (CTCs) from blood being investigated a role guiding real-time drug selection during disease progression, expecting that CTCs will comprehensively represent the full spectrum of genomic changes metastases. information is limited regarding mutational heterogeneity among and...
Abstract Here, we characterize the Arabidopsis thaliana embryo-defective mutant increased size exclusion limit2 (ise2). In contrast with wild-type embryos, ise2 mutants continue to traffic 10-kD fluorescent dextran in mid-torpedo stage of development. embryos contain branched as well simple plasmodesmata (PD) compared which only PD. Positional cloning reveals that ISE2 gene encodes a putative DEVH box RNA helicase shares sequence homology helicases involved degradation pathways other...
Abstract Introduction Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. Phosphatidylinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression protein levels, mTOR inhibitors have been shown to inhibit growth cell lines. We describe a panel patient-derived xenografts representing multiple subtypes use them test preclinical drug efficacy two inhibitors, sirolimus...
The dynamic actin cytoskeleton is important for a myriad of cellular functions, including intracellular transport, cell division, and shape. An regulator polymerization the actin-related protein2/3 (Arp2/3) complex, which nucleates new filaments. In animals, Scar/WAVE family members activate Arp2/3 complex-dependent nucleation through interactions with Abi1, Nap1, PIR121, HSCP300. Mutations in Arabidopsis thaliana genes encoding homologs complex subunits PIR121 NAP1 all show distorted...
The accurate and complete selection of candidate genomic regions from a DNA sample before sequencing is critical in molecular diagnostics. Several recently developed technologies await substantial improvements performance, cost, multiplex processing. Here we present the utility long padlock probes (LPPs) for targeted exon capture followed by array-based sequencing. We found that on average 92% 5,471 exons 524 nuclear-encoded mitochondrial genes were successfully amplified 63 individuals....
The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by loading complex (PLC) components is expected ensure the cell surface expression of stable peptide-HLA complexes. This exemplified HLA-B*08:01 in primary lymphocytes, with both level half-life at high end measured HLA-B stability hierarchies. Conversely, low on lymphocytes for three allotypes that bind...
Abstract We report the genetic, phenotypic, and biochemical analyses of Catecholamines up (Catsup), a gene that encodes negative regulator tyrosine hydroxylase (TH) activity. Mutations within this locus are semidominant lethals variable penetrance result in three broad, overlapping effective lethal phases (ELPs), indicating Catsup product is essential throughout development. Mutants from each ELP exhibit either cuticle defects or catecholamine-related abnormalities, such as melanotic...
We developed a robust and reproducible methodology to amplify human sequences in parallel for use downstream multiplexed sequence analyses. call the SMART (Spacer Multiplex Amplification Reaction), it is based, part, on padlock probe technology. As proof of principle, we used technology simultaneously 485 exons ranging from 100 500 bp genomic DNA. In multiple repetitions, >90% targets were successfully amplified with high degree uniformity, 70% falling within 10-fold range all products...
ABSTRACT The plant cytoskeleton plays a pivotal role in determining the direction of cell wall expansion, and ultimately cell’s final shape. However, mechanisms by which localized expansion events are initiated remain obscure. Mutational analysis trichome (plant hair) morphogenic pathway Arabidopsis has identified at least eight genes that determine branch number. One these genes, ZWICHEL (ZWI), encodes novel member kinesin superfamily motor proteins. Mutations ZWI gene cause reduction...
Anopheles innate immunity affects Plasmodium development and is a potential target of innovative malaria control strategies. The extent distribution nucleotide diversity in genes might provide insights into the evolutionary forces that condition pathogen-vector interactions. discovery polymorphisms an essential step towards association studies susceptibility to infection. We sequenced coding fragments 72 immune related natural populations gambiae 37 randomly chosen background measure genetic...
When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction the receptor (TCR) and co-receptor CD8. Peptides are generally critical for stable surface expression of HLA-I molecules. However, alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers thermostable detectable on surface. Additionally, HLA-B*35:01 tetramers preferentially bind CD8 to a majority blood-derived cells CD8-dependent binding...
The GTP cyclohydrolase I gene of Drosophila melanogaster, the Punch locus, encodes alternative transcripts 1.7 and 1.76 kilobases (kb).These are differentially expressed throughout development.cDNA clones representing these transcripts, cor- responding genomic regions polymerase chain reaction-amplified primer extensions 5' ends RNAs were sequenced.Both contain five exons derive from primary that extend over approximately 8 4 kb for 1.7-and 1.76-kb R N A s , respectively.Their 6'-most unique...
AbstractTyrosine hydroxylase requires the regulatory cofactor, tetrahydrobiopterin, for catecholamine biosynthesis. Because guanosine triphosphate cyclohydrolase I is rate limiting enzyme synthesis of this it has a key role in production. We show that GTP and tyrosine (TH) are co-localized Drosophila central nervous system. Mutations Punch locus, which encodes cyclohydrolase, reduce TH activity; addition cofactor to crude extracts could not fully rescue activity all mutant strains. The...
The proper control of cell expansion is vital to plant development. It responsible for shaping individual cells and, together with division, it plays a lead role in organs. Much the underlying mechanism by which expand anisotropically not understood. We are taking genetic approach isolating mutants that affect branching pattern Arabidopsis trichomes. Here we report identification four new loci trichome morphogenesis. These were named IRREGULAR TRICHOME BRANCH (ITB) because deleterious...
Determine whether variation in the HLA region is associated with development of post-traumatic sepsis and septic shock.Sepsis-related deaths remain a major source mortality after traumatic injury. Genetic characteristics may contribute to susceptibility adverse outcomes including shock. Recent advances next-generation sequencing technology now allow comprehensive genotyping region.White adult trauma patients requiring more than 2 days mechanical ventilation underwent genotyping, were...
The vast majority of microscopic life on earth consists microbes that do not grow in laboratory culture. To profile the microbial diversity environmental and clinical samples, we have devised employed molecular probe technology, which detects identifies bacteria only requirement is a short sequence contiguous bases (currently 60 bases) unique to genome organism interest. procedure relatively fast, inexpensive, customizable, robust, culture independent uses commercially available reagents...
Abstract Background: Circulating tumor cells (CTCs) in blood and disseminated (DTCs) bone marrow are being studied to monitor disease guide therapy, but the relationship between CTCs DTCs is weak may confound clinical decision-making. Because sampling easier than marrow, CTC analyses used more frequently DTC analyses, although mutational heterogeneity within both populations at single cell level not usually examined simultaneously. Methods: We MagSweeper immunomagnetically isolate from...