Robert J. Shmookler Reis
Professor
Also affiliated: University of Rome Tor Vergata (2016); University of Southern California (2012); United States Department of Veterans Affairs (1996–2017); Wayne State University (2006); University of Colorado Boulder (1997); Washington University in St. Louis (1997); University of Arkansas Medical Center (2004–2025); Central Arkansas Veterans Healthcare System (1985–2026); Geriatric Research Education and Clinical Center (1985–2024); John L. McClellan Memorial Veterans Hospital (1982–2023); Bioingénierie, Tissus et Neuroplasticité (2023); Medical Research Council (1978); McMaster University (1978–1982); University of Edinburgh (1978)
Geriatrics, College of Medicine
Research Areas
Biomedical Subjects
Biography and Research Information
OverviewAI-generated summary
Robert J. Shmookler Reis's research group investigates two primary areas: the role of PI 3-kinase in insulin-like signaling and its impact on extreme longevity, demonstrated by a ten-fold increase in lifespan in C. elegans nematodes with a null mutation, and the role of protein aggregation as a common feature of age-progressive diseases. His work explores specific proteins that either promote aggregation or hinder their clearance through proteasome and autophagosome interference.
Utilizing proteomics, his lab identifies proteins within aggregates associated with Alzheimer's and other human neurodegenerative diseases. The structural information of these proteins facilitates molecular-dynamic simulations of protein-protein and protein-drug interactions. Predictions derived from these in silico studies are then validated in vivo using models of Alzheimer's and other neurodegenerative diseases in C. elegans, cultured human cells, and mouse models of neuropathy. Molecular genetics and bioinformatics serve as complementary tools for discovering and understanding functional interactions within these disease processes.
Dr. Shmookler Reis has secured federal funding for his research, including an NIH/National Institute on Aging grant for "Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases" totaling $374,971. He has also served as PI on NIH grants focused on repurposing FDA-approved drugs for Alzheimer's disease aggregates and analyzing and treating age-dependent proteostasis failure in neurodegeneration. His work has been recognized with a BLR&D Research Career Scientist Award from NIH. He maintains a high h-index of 44, with over 5,800 citations across 173 publications, and actively collaborates with researchers at the University of Arkansas for Medical Sciences.
Research Overview
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.
Metrics
- h-index: 45
- Publications: 175
- Citations: 5,965
Positions
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Professor publications 1981–2026University of Arkansas for Medical Sciences Geriatrics, College of Medicine Institutional directory
Selected Publications
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The aggregate proteome of Caenorhabditis elegans mitochondria implicates shared mechanisms of aging and Alzheimer’s disease (2026)
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Machine Learning–Enhanced Quantitative Structure-Activity Relationship Modeling for DNA Polymerase Inhibitor Discovery: Algorithm Development and Validation (2025)
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Accelerating Discovery of Leukemia Inhibitors Using AI-Driven Quantitative Structure-Activity Relationship: Algorithm Development and Validation (2025)
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DNA Polymerase Inhibitor Discovery Using Machine Learning-Enhanced QSAR Modeling (2025)
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Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer’s-like neuropathology (2025)
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Mitochondria in aging and age-associated diseases (2025)
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Strong reduction of cryoprotectant toxicity by stress response induction (2024)
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Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction (2024)
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Model biological systems demonstrate the inducibility of pathways that strongly reduce cryoprotectant toxicity (2024)
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Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules (2024)
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Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets (2023)
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Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain (2023)
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Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan (2023)
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Protein homeostasis in the aged and diseased heart (2023)
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In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration (2023)
Federal Grants 4 $374,971 total
Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases
Analysis and therapy of age-dependent proteostasis failure in neurodegeneration
Grants & Funding
As listed on this researcher's institutional profile. Federal awards with verified records are shown above.
- Center for Studies of Host Response to Cancer Therapy NIH Co-Investigator
- Role of glutathione transferases in life span extension of C. elegans NIH Co-Investigator
- Roles of protein aggregation in Alzheimer’s and other neurodegenerative diseases NIH/NIA Principal Investigator
- Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases - Continuation - Continuation NIH/Nat. Inst. on Aging Principal Investigator
- Metabolic Mechanisms Limiting and Protecting Longevity NIH/Nat. Inst. on Aging Principal Investigator
- IDBR: TYPE A. Far-field optical thermal wave nanoscopy- Resubmission - Continuation - Continuation National Science Foundation Co-Investigator
- Senior Research Career Scientist Award Veterans Administration Principal Investigator
- Arkansas Claude Pepper Older Americans Independence Center at UAMS NIH Co-Investigator
- Polymorphic Genes Modulating Lifespan in C Elegans NIH/Nat. Inst. on Aging Principal Investigator
- Senior Research Career Scientist Award VA (Dept. of Veterans Affairs) Principal Investigator
- Early Events in Alzheimer Pathogenesis NIH Co-Principal Investigator
Collaboration Network
Top Collaborators
- Remarkable longevity and stress resistance of nematode PI3K‐null mutants
- Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants
- Discrimination of Primer 3′-Nucleotide Mismatch by Taq DNA Polymerase during Polymerase Chain Reaction
- Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs
- Aspirin Inhibits Oxidant Stress, Reduces Age-Associated Functional Declines, and Extends Lifespan of Caenorhabditis elegans
Showing 5 of 57 shared publications
- Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs
- Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls
- Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation
- Proteins in aggregates functionally impact multiple neurodegenerative disease models by forming proteasome‐blocking complexes
- Proteins that accumulate with age in human skeletal-muscle aggregates contribute to declines in muscle mass and function in Caenorhabditis elegans
Showing 5 of 33 shared publications
- Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.
- Variability of DNA methylation patterns during serial passage of human diploid fibroblasts
- Extrachromosomal circular copies of an ‘inter-Alu’ unstable sequence in human DNA are amplified during in vitro and in vivo ageing
- Interclonal variation in methylation patterns for expressed and non-expressed genes
- Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts
Showing 5 of 18 shared publications
- Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer’s Disease
- Intrinsically disordered proteins identified in the aggregate proteome serve as biomarkers of neurodegeneration
- “Protein aggregates” contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation
- Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases
- A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease
Showing 5 of 18 shared publications
- Dysfunctional homologous recombination mediates genomic instability and progression in myeloma
- Telomerase inhibition by peptide nucleic acids reverses `immortality' of transformed human cells
- Elevated Recombination in Immortal Human Cells Is Mediated by HsRAD51 Recombinase
- Telomerase Inhibition and Cell Growth Arrest After Telomestatin Treatment in Multiple Myeloma
- Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome
Showing 5 of 16 shared publications
- Structural modeling of GSK3β implicates the inactive (DFG-out) conformation as the target bound by TDZD analogs
- Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation
- Mitochondria in aging and age-associated diseases
- Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
Showing 5 of 12 shared publications
- Remarkable longevity and stress resistance of nematode PI3K‐null mutants
- Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants
- Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls
- A universal transcriptomic signature of age reveals the temporal scaling of Caenorhabditis elegans aging trajectories
- Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation
Showing 5 of 11 shared publications
- Remarkable longevity and stress resistance of nematode PI3K‐null mutants
- Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants
- Discrimination of Primer 3′-Nucleotide Mismatch by Taq DNA Polymerase during Polymerase Chain Reaction
- Chromosomal Mapping of Osteopenia-Associated Quantitative Trait Loci Using Closely Related Mouse Strains
- Genetic Mapping of Quantitative Trait Loci Governing Longevity of Caenorhabditis elegans in Recombinant-Inbred Progeny of a Bergerac-BO × RC301 Interstrain Cross
Showing 5 of 10 shared publications
- Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation
- Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation
- Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases
- A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
Showing 5 of 9 shared publications
- Extrachromosomal circular copies of an ‘inter-Alu’ unstable sequence in human DNA are amplified during in vitro and in vivo ageing
- Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts
- Amplification of inter-Alu extrachromosomal DNA during cellular ageing: retraction and explanation
- Genome Alteration during In Vitro and In Vivo Aging: Amplification of Extrachromosomal Circular DNA Molecules Containing a Chromosomal Sequence of Variable Repeat Frequency
- Extrachromosomal Circular DNA and Aging Cells
Showing 5 of 7 shared publications
- Dysfunctional homologous recombination mediates genomic instability and progression in myeloma
- Telomerase Inhibition and Cell Growth Arrest After Telomestatin Treatment in Multiple Myeloma
- Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome
- Interaction of Adeno-Associated Virus Rep78 with SV40 T Antigen: Implications in Rep Protein Expression Leading to the Inhibition of SV40-Mediated Cell Proliferation
- Expression of AAV Rep Proteins in SV40-Transformed and Untransformed Cells: Reciprocal Interaction with Host DNA Synthesis
Showing 5 of 7 shared publications
- Structural modeling of GSK3β implicates the inactive (DFG-out) conformation as the target bound by TDZD analogs
- Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation
- Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases
- A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
Showing 5 of 7 shared publications
- Structural modeling of GSK3β implicates the inactive (DFG-out) conformation as the target bound by TDZD analogs
- Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation
- Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases
- A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
Showing 5 of 7 shared publications
- Lifespan and stress resistance of Caenorhabditis elegans are increased by expression of glutathione transferases capable of metabolizing the lipid peroxidation product 4‐hydroxynonenal
- Chromosomal Mapping of Osteopenia-Associated Quantitative Trait Loci Using Closely Related Mouse Strains
- Lifespan extension in hypomorphic daf‐2 mutants of Caenorhabditis elegans is partially mediated by glutathione transferase CeGSTP2‐2
- Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts
- A novel locus on the X chromosome regulates post-maturity bone density changes in mice
Showing 5 of 6 shared publications
- A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition
- Genomic Instability in Multiple Myeloma
- Advances in understanding the molecular basis of clonal hematopoiesis
- Dinaciclib, a CDK Inhibitor, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition
- A Peptide Nucleic Acid Targeting Nuclear Rad51 Sensitizes Myeloma Cells to Melphalan Chemotoxicity Both in Vitro and in Vivo
Showing 5 of 6 shared publications
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