A5079292887- Pancreatic function and diabetes
- Erythrocyte Function and Pathophysiology
- Lipid Membrane Structure and Behavior
- Insect and Pesticide Research
- Neurobiology and Insect Physiology Research
- Genetic Neurodegenerative Diseases
- Calcium signaling and nucleotide metabolism
- ATP Synthase and ATPases Research
- Statistical Methods in Clinical Trials
- Insect-Plant Interactions and Control
- Cellular transport and secretion
- bioluminescence and chemiluminescence research
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Ion Transport and Channel Regulation
- Pharmacogenetics and Drug Metabolism
- Sphingolipid Metabolism and Signaling
- Fungal and yeast genetics research
- Phagocytosis and Immune Regulation
- Animal Ecology and Behavior Studies
- Muscle Physiology and Disorders
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Blood properties and coagulation
- Glycosylation and Glycoproteins Research
University of Pittsburgh
2011-2023
Institute for Neurodegenerative Disorders
2013-2023
Vanderbilt University Medical Center
2020-2021
Vanderbilt University
2016-2020
Fraunhofer Institute for Factory Operation and Automation
2020
Central Michigan University
2010
Field Neurosciences Institute
2010
Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila investigate constraints on repeated evolution unrelated herbivorous insects toxic cardiac glycosides, which primarily occurs via a small subset possible functionally-relevant substitutions Na+,K+-ATPase. Surprisingly, we find frequently observed adaptive at two sites, 111 and 122, are lethal when homozygous adult heterozygotes...
Triosephosphate isomerase (TPI) is a glycolytic enzyme that converts dihydroxyacetone phosphate (DHAP) into glyceraldehyde-3-phosphate (GAP). Glycolytic dysfunction leads to metabolic diseases collectively known as enzymopathies. Of these enzymopathies, TPI deficiency unique in the severity of neurological symptoms. The Drosophila sugarkill mutant closely models and encodes protein prematurely degraded by proteasome. This result led us question whether catalytic activity was critical...
Significance The asymmetric organization of cellular membranes is a critical determinant cell and tissue physiology. Phospholipid flippases are principle regulators this membrane asymmetry, understanding their mechanics will be important for determining how deficiencies these enzymes lead to several different diseases. current study has identified key structural mechanism the exclusion sphingomyelin as flippase substrate. Understanding unique recognize transport substrates can direct...
Triosephosphate isomerase (TPI) deficiency is a poorly understood disease characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and early death. TPI one of group diseases known as glycolytic enzymopathies, but unique for its severe patient neuropathology mortality. The caused missense mutations dysfunction in the enzyme, TPI. Previous studies have detailed structural catalytic changes elicited disease-associated substitutions, samples erythrocytes yielded insight into...
The 17- amino acid N-terminal segment of the Huntingtin protein, htt(NT), grows into stable α-helix rich oligomeric aggregates when incubated under physiological conditions. We examined 15 scrambled sequence versions an htt(NT) peptide for their stabilities against aggregation in aqueous solution at low micromolar concentration and Surprisingly, given derivation from a that readily assembles highly α-helical fail to convert β-structure, we found three these peptides rapidly grow amyloid-like...
The plasma membrane of a cell is characterized by an asymmetric distribution lipid species across the exofacial and cytofacial aspects bilayer. Regulation asymmetry fundamental characteristic biology crucial for signal transduction, vesicle transport, division. type IV family P-ATPases, or P4-ATPases, establishes selection transfer subset lipids from lumenal leaflet to aspect It unclear how P4-ATPases sort through spectrum identify their desired substrate(s) environment modulates this...
Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical technical challenges. Vanderbilt University Medical Center initiated panel testing in 2010, added CYP2D6 2017, released CDS SSRIs 2020. We systematically reinterpreted historic CYP2C19 genotypes update phenotypes current...
Toxic cardiotonic steroids (CTS) act as a defense mechanism in many firefly species (Lampyridae) by inhibiting crucial enzyme called Na+,K+-ATPase (NKA). While most fireflies produce these toxins internally, of the genus Photuris acquire them from surprising source: predation on other fireflies. The contrasting physiology toxin exposure and sequestration between genera suggests that distinct strategies may be required to prevent self-intoxication. Our study demonstrates both their prey have...
Abstract The plasma membrane of a cell is characterized by an asymmetric distribution lipid species across the exofacial and cytofacial aspects bilayer. regulation asymmetry fundamental characteristic biology, crucial for signal transduction, vesicle transport, division. type-IV family P-ATPases, or P4-ATPases, establish selection transfer subset lipids from lumenal leaflet to aspect It still unclear how these enzymes sort through spectrum within identify their desired substrate(s)...
Abstract Lipid transport is an essential process with manifest importance to human health and disease. Phospholipid flippases (P4-ATPases) lipids across the membrane bilayer, are involved in signal transduction, cell division, vesicular transport. Mutations flippase genes cause or contribute a host of diseases such as cholestasis, neurological deficits, immunological dysfunction, metabolic Genome-wide association studies have shown that ATP10A ATP10D variants associated increased risk...
Abstract Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila investigate constraints on repeated evolution unrelated herbivorous insects toxic cardiac glycosides, which primarily occurs via a small subset possible functionally-relevant substitutions Na + ,K -ATPase. Surprisingly, we find frequently observed adaptive at two sites, 111 and 122, are lethal when homozygous adult...