Robert J. Shmookler Reis
Professor
University of Arkansas for Medical Sciences
faculty
Geriatrics, College of Medicine
Research Areas
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Biography and Research Information
OverviewAI-generated summary
Robert J. Shmookler Reis, Professor in the Department of Geriatrics at the University of Arkansas for Medical Sciences, investigates the molecular mechanisms underlying aging and age-related diseases. His research group focuses on two primary areas: the role of PI 3-kinase in insulin-like signaling and its impact on extreme longevity, and the role of protein aggregation in age-progressive diseases. The group has demonstrated a significant increase in lifespan in *C. elegans* nematodes with a PI 3-kinase null mutation.
In the realm of protein aggregation, Reis's lab studies proteins that either promote aggregation or hinder their clearance through proteasomal and autophagosomal pathways. They employ proteomics to identify proteins within aggregates associated with Alzheimer's disease and other human neurodegenerative conditions. Structural analyses and molecular-dynamic simulations are used to predict protein-protein and protein-drug interactions, with subsequent in silico predictions being validated in vivo using models of neurodegenerative diseases in *C. elegans*, human cell cultures, and mouse models. Molecular genetics and bioinformatics are utilized as complementary tools to elucidate functional interactions.
Reis has a distinguished publication record with 173 total publications and a citation count of 5,659, yielding an h-index of 43. He has served as PI on a $374,971 NIH/National Institute on Aging grant focused on inferring common pathways underlying neurodegeneration and other age-progressive diseases. His collaborative network includes several researchers from the University of Arkansas for Medical Sciences, such as Srinivas Ayyadevara, Meenakshisundaram Balasubramaniam, Akshatha Ganne, and Nirjal Mainali.
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: 43
- Publications: 173
- Citations: 5,659
Selected Publications
- Accelerating Discovery of Leukemia Inhibitors Using AI-Driven Quantitative Structure-Activity Relationship: Algorithm Development and Validation (2025) DOI
- Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer’s-like neuropathology (2025) DOI
- Strong reduction of cryoprotectant toxicity by stress response induction (2024) DOI
- Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction (2024) DOI
- Model biological systems demonstrate the inducibility of pathways that strongly reduce cryoprotectant toxicity (2024) DOI
- Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules (2024) DOI
- Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets (2023) DOI
- Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain (2023) DOI
- Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan (2023) DOI
- Protein homeostasis in the aged and diseased heart (2023) DOI
- In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration (2023) DOI
- Physiological Consequences of Targeting 14-3-3 and Its Interacting Partners in Neurodegenerative Diseases (2022) DOI
- Machine-learning analysis of intrinsically disordered proteins identifies key factors that contribute to neurodegeneration-related aggregation (2022) DOI
- Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer’s Disease (2022) DOI
- In Silico Analysis of TUBA4A Mutations in Amyotrophic Lateral Sclerosis to Define Mechanisms of Microtubule Disintegration (2022) DOI
Federal Grants 1 $374,971 total
Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases
Grants & Funding
- No FP attached Quantum Pharmaceuticals Ltd Principal Investigator
- Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases NIH/Nat. Inst. on Aging Principal Investigator
- 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
- Repurposing FDA-approved drugs to disrupt tau- and amyloid-associated protein-protein interactions in Alzheimer's disease aggregates VA (I01 Dept. of Veterans Affairs) Principal Investigator
- Roles of protein aggregation in Alzheimer’s and other neurodegenerative diseases NIH/NIA Principal Investigator
- Analysis and Therapy of Age-Dependent Proteostasis Failure in Neurodegeneration Veterans Administration Principal Investigator
- Inference of Common Pathways Underlying Neurodegeneration & Other Age-Progressive Diseases - Continuation - Continuation NIH/Nat. Inst. on Aging Principal Investigator
Collaborators
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