- Genetic Associations and Epidemiology
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Metabolism and Genetic Disorders
- Protease and Inhibitor Mechanisms
- Viral Infections and Vectors
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Folate and B Vitamins Research
- ATP Synthase and ATPases Research
- Biochemical and Structural Characterization
- Epigenetics and DNA Methylation
- Viral gastroenteritis research and epidemiology
- Genetic diversity and population structure
- Monoclonal and Polyclonal Antibodies Research
- Virology and Viral Diseases
- Cellular transport and secretion
- Trace Elements in Health
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- Chromosomal and Genetic Variations
- Enzyme Structure and Function
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Adipokines, Inflammation, and Metabolic Diseases
Duke University Hospital
2010-2020
Duke Medical Center
2010-2020
Case Western Reserve University
2015
University School
2015
Broad Institute
2007-2009
Harvard University
2007-2008
Massachusetts Institute of Technology
2007
Persistently low white blood cell count (WBC) and neutrophil is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference WBC between Americans European Americans. To specific genetic change responsible this association, we analyzed genotype phenotype data from 6,005...
Population geneticists often study small numbers of carefully chosen loci, but it has become possible to obtain orders magnitude for more data from overlaps genome sequences. Here, we generate tens millions base pairs multiple sequence alignments combinations three western chimpanzees, central an eastern chimpanzee, a bonobo, human, orangutan, and macaque. Analysis provides precise understanding demographic history than was previously available. We show that bonobos common chimpanzees were...
Inositol diphosphates (PP-IPs), also known as inositol pyrophosphates, are high-energy cellular signaling codes involved in nutrient and regulatory responses. We report that the evolutionarily conserved gene product, Vip1, possesses autonomous kinase pyrophosphatase domains capable of synthesis destruction D-1 PP-IPs. Our studies provide atomic-resolution structures PP-IP products unequivocally define Vip1 product is a highly selective 1-kinase 1-pyrophosphatase enzyme whose activities arise...
The unconventional mRNA capping enzyme (GDP polyribonucleotidyltransferase, PRNTase; block V) domain in RNA polymerase L proteins of non-segmented negative strand (NNS) viruses (e.g. rabies, measles, Ebola) contains five collinear sequence elements, Rx(3)Wx(3-8)ΦxGxζx(P/A) (motif A; Φ, hydrophobic; ζ, hydrophilic), (Y/W)ΦGSxT B), W C), HR D) and ζxxΦx(F/Y)QxxΦ E). We performed site-directed mutagenesis the protein vesicular stomatitis virus (VSV, a prototypic NNS virus) to examine...
GRP94 (gp96)-peptide complexes can be internalized by APCs and their associated peptides cross-presented to yield activation of CD8(+) T cells. Investigations into the identity (or identities) surface receptors have yielded conflicting results, particularly with respect CD91 (LRP1), which has been proposed essential for recognition uptake. To assess function in binding endocytosis, these parameters were examined mouse embryonic fibroblast (MEF) cell lines whose expression was either reduced...