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Reis, Robert

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My research group has been focused for the last 5 years on two areas: (1.) the role of PI 3-kinase in insulin-like signaling and extreme longevity, extending to a 10-fold increase in lifespan for C. elegans nematodes carrying a null mutation; and (2.) protein aggregation as a unifying feature of many or all age-progressive diseases. We have pursued specific aggregate proteins that favor the formation of aggregates (by promoting protein coallescence) or disrupt their clearance (through interference with proteasomes and autophagosomes). We use proteomics to identify proteins in aggregates of Alzheimer's and other human neurodegenerative diseases; their known or predicted structures allow molecular-dynamic simulations of protein-protein and protein-drug interactions. Predictions from in silico studies are then tested in vivo using models of Alzheimer’s and other human neurodegenerative diseases, in the nematode C. elegans, in cultured human cells, and in mouse models of neuropathy. Molecular genetics and bioinformatics provide complementary tools to discover and understand functional interactions. Water under the bridge (previous research): From the start of my research career, I have been fascinated by the genetic regulation of longevity and age-associated diseases. My group characterized a number of mutations that have large effects on lifespan in the nematode C. elegans. We also used gene mapping combined with bioinformatics approaches to discover and characterize the natural variation in genes that modulate lifespan. We found that Rec-8 protein (a cohesin) alters lifespan in nematodes and yeast, and a colleague then showed that it also contributed to the exceptional longevity of bowhead whales. In mammalian genetics, we were the first to identify the Pirin gene on the X chromosome as a determinant of post-menopausal bone loss in women, a discovery subsequently confirmed in a Chinese population. We also pioneered studies of homologous recombination (HR) and its roles in the etiology and subsequent progression of myeloma, prostate and breast cancers. Data from our laboratory, and subsequently many others, support the hypothesis that HR generates genetic diversity from which more highly oncogenic clones emerge by cell selection. We have exploited the heavy dependence of cancer cells on HR to develop synergistic combinations of chemotherapeutic drugs.

One or more keywords matched the following items that are connected to Reis, Robert

Item Type	Name
Academic Article	A novel locus on the X chromosome regulates post-maturity bone density changes in mice.
Academic Article	Chromosomal mapping of osteopenia-associated quantitative trait loci using closely related mouse strains.
Academic Article	Molecular pathology of aging and its implications for senescent coronary atherosclerosis.
Concept	Coronary Artery Disease
Concept	Huntington Disease
Concept	Alzheimer Disease
Concept	Bone Diseases, Metabolic
Concept	Cardiovascular Diseases
Concept	Disease Progression
Concept	Neurodegenerative Diseases
Concept	Genetic Predisposition to Disease
Concept	Disease Models, Animal
Academic Article	A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells to melphalan treatment.
Academic Article	Dysfunctional homologous recombination mediates genomic instability and progression in myeloma.
Academic Article	Proteins in aggregates functionally impact multiple neurodegenerative disease models by forming proteasome-blocking complexes.
Academic Article	Animal models for discovery and assessment of genetic determinants of osteoporosis.
Academic Article	Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles.
Academic Article	Histoplasma capsulatum and Caenorhabditis elegans: a simple nematode model for an innate immune response to fungal infection.
Academic Article	Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls.
Academic Article	Cellular and molecular biomarkers indicate precocious in vitro senescence in fibroblasts from SAMP6 mice. Evidence supporting a murine model of premature senescence and osteopenia.
Academic Article	Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.
Academic Article	Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs.
Academic Article	Structural insights into pro-aggregation effects of C. elegans CRAM-1 and its human ortholog SERF2.
Academic Article	Functional assessments through novel proteomics approaches: Application to insulin/IGF signaling in neurodegenerative disease'.
Grant	Role of glutathione transferases in life span extension of C. elegans
Grant	Early Events in Alzheimer Pathogenesis
Grant	Arkansas Claude Pepper Older Americans Independence Center at UAMS
Grant	Roles of protein aggregation in Alzheimer’s and other neurodegenerative diseases
Grant	Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases
Academic Article	Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases.
Academic Article	A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer's Disease.
Academic Article	"Protein aggregates" contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation.
Academic Article	Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer's disease.
Academic Article	Intrinsically disordered proteins identified in the aggregate proteome serve as biomarkers of neurodegeneration.
Academic Article	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington's disease.
Academic Article	Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer's Disease.
Academic Article	Physiological Consequences of Targeting 14-3-3 and Its Interacting Partners in Neurodegenerative Diseases.
Academic Article	Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer's disease by targeted small molecules.

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