Robert J. Shmookler Reis
Professor
Also affiliated: University of Rome Tor Vergata (2016); University of Southern California (2012); United States Department of Veterans Affairs (1985–2017); California Department of Transportation (2003); Wayne State University (2006); University of Colorado Boulder (1997); British Geriatrics Society (2001–2005); University of Arkansas Medical Center (1983–2023); Central Arkansas Veterans Healthcare System (1985–2026); Geriatric Research Education and Clinical Center (1982–2024); Institute on Aging (2016–2025); Department of Veterans Affairs (2005); John L. McClellan Memorial Veterans Hospital (1989–2023); Reynolds American (United States) (2017); Arkansas Department of Agriculture (2013); Memorial Hospital (1996); Institute of Pharmacology (2005); Virginia Department of Transportation (2003); Medical Research Council (1978); McMaster University (1978–1982); University of Edinburgh (1978)
Faculty Researcher
Geriatrics, College of Medicine
Research Areas
Biomedical Subjects
Biography and Research Information
OverviewAI-generated summary
Robert J. Shmookler Reis's research group investigates the role of PI 3-kinase in insulin-like signaling and its connection to extreme longevity, with studies demonstrating a tenfold increase in lifespan for C. elegans nematodes with a specific mutation. The group also focuses on protein aggregation as a common feature across age-progressive diseases. Their work explores specific proteins that either promote aggregate formation or hinder their clearance by proteasomes and autophagosomes.
Utilizing proteomics, the researchers identify proteins within aggregates associated with Alzheimer's disease and other human neurodegenerative conditions. Structural analysis of these proteins allows for molecular-dynamic simulations of protein-protein and protein-drug interactions. These in silico predictions are then validated in vivo using models of neurodegenerative diseases in C. elegans, cultured human cells, and mouse models. Molecular genetics and bioinformatics tools complement these efforts to understand functional interactions.
With an h-index of 44 and 173 total publications, Shmookler Reis has received funding for his research, including a $374,971 NIH/National Institute on Aging grant focused on inferring common pathways underlying neurodegeneration and other age-progressive diseases. He collaborates with several researchers at the University of Arkansas for Medical Sciences, including Srinivas Ayyadevara and Meenakshisundaram Balasubramaniam.
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: 44
- Publications: 173
- Citations: 5,782
Selected Publications
-
The aggregate proteome of Caenorhabditis elegans mitochondria implicates shared mechanisms of aging and Alzheimer’s disease (2026)
-
Machine Learning–Enhanced Quantitative Structure-Activity Relationship Modeling for DNA Polymerase Inhibitor Discovery: Algorithm Development and Validation (2025)
-
Accelerating Discovery of Leukemia Inhibitors Using AI-Driven Quantitative Structure-Activity Relationship: Algorithm Development and Validation (2025)
-
Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer’s-like neuropathology (2025)
-
Mitochondria in aging and age-associated diseases (2025)
-
Strong reduction of cryoprotectant toxicity by stress response induction (2024)
-
Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction (2024)
-
Model biological systems demonstrate the inducibility of pathways that strongly reduce cryoprotectant toxicity (2024)
-
Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules (2024)
-
Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets (2023)
-
Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain (2023)
-
Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan (2023)
-
Protein homeostasis in the aged and diseased heart (2023)
-
In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration (2023)
-
Physiological Consequences of Targeting 14-3-3 and Its Interacting Partners in Neurodegenerative Diseases (2022)
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
- 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
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
Showing 5 of 17 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
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
Showing 5 of 15 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
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration
Showing 5 of 12 shared publications
- 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
- Physiological Consequences of Targeting 14-3-3 and Its Interacting Partners in Neurodegenerative Diseases
- Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction
Showing 5 of 10 shared publications
- “Protein aggregates” contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
- Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction
- Mitochondria in aging and age-associated diseases
- Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction
- Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets
- Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer’s-like neuropathology
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration
- In Silico Analysis of TUBA4A Mutations in Amyotrophic Lateral Sclerosis to Define Mechanisms of Microtubule Disintegration
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer’s disease
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration
- In Silico Analysis of TUBA4A Mutations in Amyotrophic Lateral Sclerosis to Define Mechanisms of Microtubule Disintegration
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration
- In Silico Analysis of TUBA4A Mutations in Amyotrophic Lateral Sclerosis to Define Mechanisms of Microtubule Disintegration
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration
- In Silico Analysis of TUBA4A Mutations in Amyotrophic Lateral Sclerosis to Define Mechanisms of Microtubule Disintegration
- Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain
- Protein homeostasis in the aged and diseased heart
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
- Accelerating Discovery of Leukemia Inhibitors Using AI-Driven Quantitative Structure-Activity Relationship: Algorithm Development and Validation
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
Similar Researchers
Based on overlapping research topics