M. A. Nalls
A5041676520- Parkinson's Disease Mechanisms and Treatments
- Genetic Associations and Epidemiology
- Lysosomal Storage Disorders Research
- Neurological diseases and metabolism
- Cellular transport and secretion
- Cancer-related molecular mechanisms research
- Carbohydrate Chemistry and Synthesis
- Amyotrophic Lateral Sclerosis Research
- Nutrition, Genetics, and Disease
- Genetic and phenotypic traits in livestock
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Health, Environment, Cognitive Aging
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Machine Learning in Healthcare
- Lipid metabolism and disorders
- Advanced Proteomics Techniques and Applications
- Studies on Chitinases and Chitosanases
- Health and Well-being Studies
- Menopause: Health Impacts and Treatments
- Chemokine receptors and signaling
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
National Institute on Aging
2009-2025
National Institutes of Health
2011-2025
Data Tecnica International (United States)
2018-2025
Institute on Aging
2025
National Institute of Neurological Disorders and Stroke
2024-2025
University Memory and Aging Center
2018
University of California, San Francisco
2018
University College London
2018
University of Reading
2018
Texas Tech University
2018
Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain GBA ethnically diverse group disease.Sixteen centers participated our international, collaborative study: five from Americas, six Europe, two Israel, and three Asia. Each center genotyped standard DNA panel permit comparison genotyping results across centers. Genotypes phenotypic...
Abstract Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large (total n = 82,337 cases and controls), we utilized a previously validated approach to identify overlap reveal pathways between progressive supranuclear palsy (PSP),...
Abstract Elucidating the genetic contributions to Parkinson’s disease (PD) etiology across diverse ancestries is a critical priority for development of targeted therapies in global context. We conducted largest sequencing characterization potentially disease-causing, protein-altering and splicing mutations 710 cases 11,827 controls from genetically predicted African or admixed ancestries. explored copy number variants (CNVs) runs homozygosity (ROHs) prioritized early onset familial cases....
Abstract Backgrounds Biomedical research requires sophisticated understanding and reasoning across multiple specializations. While large language models (LLMs) show promise in scientific applications, their capability to safely accurately support complex biomedical remains uncertain. Methods We present CARDBiomedBench , a novel question-and-answer benchmark for evaluating LLMs research. For our pilot implementation, we focus on neurodegenerative diseases (NDDs), domain requiring integration...
Endemic viral infections with low pathogenicity are often overlooked due to their mild symptoms, yet they can exert long-term effects on cellular function and contribute disease pathogenesis. While have been implicated in neurodegenerative disorders, impact the neuronal proteome remains poorly understood. Here, we differentiated human induced pluripotent stem cells (KOLF2.1J) into mature neurons investigate virus-induced proteomic changes following infection five neurotropic endemic viruses:...
Abstract LRRK2 -PD represents the most common form of autosomal dominant Parkinson’s disease. We identified p.L1795F variant in three families and six additional unrelated cases using genetic data from over 50,000 individuals. Carriers with available genotyping shared a haplotype. The clinical presentation resembles other forms. Combined published functional evidence showing strongly enhanced kinase activity, we provide that is pathogenic.
Microglia are immune cells of the brain and act as major antigen presenting cells. Antigen presentation involves human leukocyte (HLA) complex, which is implicated in genetic risk multiple neurodegenerative diseases. How HLA affects function microglia context disease remains unclear. Here, we investigated epitopes their protein interactome induced pluripotent stem cell (iPSC)-derived microglia-like (iMGLs) using systematic mass spectrometry (MS)-based immunopeptidomics, whole-cell...
There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci PD progression. The biology of progression is likely to be central importance in defining mechanisms that can used develop new treatments. We studied 6766 patients, over 15,340 visits with a mean follow-up between 4.2 and 15.7 years carried out survival studies time motor endpoint, defined by reaching Hoehn Yahr stage 3 or greater, death (mortality). was...
Parkinson's disease (PD) is an incurable, progressive and common movement disorder that increasing in incidence globally because of population aging. We hypothesized the landscape rare, protein-altering variants could provide further insights into pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases 5,512 controls Asian ancestry. showed GBA1 SMPD1 were significantly associated with risk, replication a 5,585 5,642 controls. refined variant...
Lens transparency, or the magnitude of cataract severity, is a potential in vivo marker aging distinguishable from diagnosed cataract. To explore lens transparency as aging, we determined its association with leukocyte telomere length (LTL) measured quantitative polymerase chain reaction. Cataract severity was directly 259 participants, and prevalent incident surgery were ascertained 2,750 participants Health, Aging, Body Composition Study. LTL unassociated clinical outcomes. Six had...
Background and purpose Although the genetic contribution to stroke risk is well known, it remains unclear if young‐onset has a stronger than old‐onset stroke. This study aims compare heritability of ischaemic between young old, using common variants from whole‐genome array data in population‐based samples. Methods analysis included 4050 cases 5765 controls six populations European ancestry; 47% were (age < 55 years). To quantify for these unrelated individuals, pairwise relatedness was...
<h3>Background</h3> Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, has a higher prevalence in African Americans than Caucasians. Ankle–arm index (AAI) the ratio of systolic blood pressure leg to that arm, and, when low, marker PAD. <h3>Methods</h3> The authors used an admixture mapping approach search for genetic loci low AAI. Using data from 1040 American participants observational, population based Health, Aging, Body Composition Study who were...
The neuroanatomical profile of behavioral variant frontotemporal dementia (bvFTD) suggests a common biological etiology disease despite disparate pathologic causes; we investigated the genetic underpinnings this selective regional vulnerability to identify new risk factors for bvFTD.We used recently developed analytical techniques designed address limitations genome-wide association studies generate protein interaction network 63 bvFTD genes. We characterized using gene expression data from...
Abstract Recently, a novel African ancestry specific Parkinson’s disease (PD) risk signal was identified at the gene encoding glucocerebrosidase ( GBA1 ). This variant (rs3115534-G) is carried by ∼50% of West PD cases and imparts dose-dependent increase in for disease. The has varied frequencies across groups, but almost absent European Asian populations. high clinical therapeutic interest. Damaging bi-allelic protein-coding variants cause Gaucher mono-allelic confer Dementia with Lewy...
Abstract In this paper, we leveraged Large Language Models(LLMs) to accelerate data wrangling and automate labor-intensive aspects of discovery harmonization. This work promotes interoperability standards enhances discovery, facilitating AI-readiness in biomedical science with the generation Common Data Elements (CDEs) as key harmonizing multiple datasets. Thirty-one studies, various ontologies, medical coding systems served source material create CDEs from which available metadata context...