A5053465701- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Gut microbiota and health
- Genetics, Aging, and Longevity in Model Organisms
- Cellular transport and secretion
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- Metabolomics and Mass Spectrometry Studies
- Genetic Syndromes and Imprinting
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Machine Learning in Bioinformatics
- Bipolar Disorder and Treatment
- Clostridium difficile and Clostridium perfringens research
- Glycosylation and Glycoproteins Research
- Telemedicine and Telehealth Implementation
- Pharmacy and Medical Practices
- Congenital heart defects research
- Sharing Economy and Platforms
- RNA regulation and disease
- PI3K/AKT/mTOR signaling in cancer
- Amyotrophic Lateral Sclerosis Research
- Patient Satisfaction in Healthcare
Baylor College of Medicine
2020-2025
Neurological Research Institute
2022-2025
Texas Children's Hospital
2022-2025
Western University
2024
Michael E. DeBakey VA Medical Center
2024
University of Tennessee Health Science Center
2023
United States Department of Defense
2023
59th Medical Wing
2023
University of California, Los Angeles
2015-2018
UCLA Health
2016
The role of the human microbiome in health and disease is increasingly appreciated. We studied composition microbial communities present blood across 192 individuals, including healthy controls patients with three disorders affecting brain: schizophrenia, amyotrophic lateral sclerosis, bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate reads, we performed profiling transcripts detected whole blood. were able to detect a wide range bacterial archaeal phyla...
Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits myelination and white matter integrity; however, direct etiological genetic cellular evidence has thus far been lacking. Here, we implement a family-based approach for discovery combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation two rare...
Tau neurofibrillary tangle pathology characterizes Alzheimer's disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome proteome or differentiated Tau- versus age-dependent changes.Paired, longitudinal RNA-sequencing mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal human wildtype (TauWT) mutant form causing frontotemporal dementia...
Heterozygous variants in the glucocerebrosidase ( GBA ) gene are common and potent risk factors for Parkinson’s disease (PD). also causes autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, emerging evidence from human genetics implicates many other LSD genes PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 requirements aging adult Drosophila brain potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms...
We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be toddler or at best preschooler, even unto occasion death age 20 years. Her life-long physician felt that disorder unique world and future treatments for age-related diseases might emerge from its study. The objectives our research were determine if other such cases exist, so, whether aging is...
Sequence diversity within a family of functional enzymes provides platform for elucidating structure-function relationships and protein engineering to improve properties important applications. Access nature's vast sequence is often limited by the fact that only few have been characterized in given family. Here, we recombined catalytic domains three glycoside hydrolase 48 bacterial cellulases (Cel48; EC 3.2.1.176) - Clostridium cellulolyticum CelF, stercorarium CelY, thermocellum CelS create...
We introduce a method for identifying elements of protein structure that can be shuffled to make chimeric proteins from two or more homologous parents. Formulating recombination as graph-partitioning problem allows us identify noncontiguous segments the sequence should inherited together in progeny proteins. demonstrate this approach by constructing chimera β-glucosidases different kingdoms life. Although protein's alpha-beta barrel fold has no obvious subdomains recombination, SCHEMA...
Bipolar disorder (BD) is a highly heritable mood with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes difficulty in adequately accounting for confounders like medication use.We performed differential expression analysis well-characterized case-control (Nsubjects = 480) by RNA sequencing of whole blood. We further co-expression network analysis, functional enrichment, cell...
Parkinson's disease (PD) starts decades before symptoms appear, usually in the later of life, when age-related changes are occurring. To identify molecular early course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) neurons performed longitudinal bulk transcriptomics proteomics on brains at six time points across lifespan compared data to healthy control flies as well human post-mortem brain datasets. We found that translational energy...
Aging is a major risk factor for Alzheimer's disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in Drosophila with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- aging-induced gene strongly overlap (93%), they differ the affected cell types. In contrast to broad impact aging, tau-triggered changes are polarized excitatory neurons glia....
Noncontiguous recombination (NCR) is a method to identify pieces of structure that can be swapped among homologous proteins create new, chimeric proteins. These "blocks" are encoded by elements sequence not necessarily contiguous along the polypeptide chain. We used NCR design library in which blocks from Hypocrea jecorina cellobiohydrolase I (Cel7A) and its two thermostable homologues Talaromyces emersonii Chaetomium thermophilum shuffled 531,438 possible enzymes. constructed maximally...
Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of plasticity, mechanisms driving are unknown. Adult-born neurons within olfactory bulb have proven to be a powerful model for studying providing broad accessible avenue into neuron development, migration, integration. We others shown that efficient adult-born integration hinges presynaptic activity in form diverse signaling...
The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. brain dependent on B6 its neurotransmitter balance. To obtain insight into the genetic determinants homeostasis, we conducted a genome-wide association study (GWAS) vitamers (PL), PLP and degradation product pyridoxic acid (PA). We collected unique sample set cerebrospinal fluid (CSF) plasma from same healthy subjects Dutch ancestry (n = 493) included concentrations ratios in between these body...
Much Internet scholarship tends to analyze the at an inappropriate level of abstraction; focusing on as one medium, when -- by design nearly all significant facts for certain questions are be found application and its associated protocols. The article suggests that application-centered thinking makes a better tool hard questions, such First Amendment (such filtering) private ordering.
3105 Background: FOLFIRINOX has emerged as the optimal 1 st -line treatment option for pts with advanced PDAC and good performance status; whether it can serve backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is evaluate combination saridegib, a novel oral agent that inhibits Hh signaling pathway. In preclinical models PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma increasing...
New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation mTORC1 activity is not required for early (6 h) protection against DXR-induced damage; and 3) fasting increases expression intestinal stem cell repair genes, even when dysregulated, highlighting fasting’s crucial role regulating mTORC1-dependent independent mechanisms dynamic recovery process.
This review examines the complex role of Pin1 in development and treatment cancer. is only peptidyl–prolyl isomerase (PPIase) that can recognize isomerize phosphorylated Ser/Thr-Pro peptide bonds. catalyzes a structural change motifs modulate protein function thereby impact cell cycle regulation tumorigenesis. The molecular mechanisms by which contributes to oncogenesis are reviewed, including overexpression its correlation with poor cancer prognosis, contribution aggressive tumor phenotypes...
Abstract The role of the human microbiome in health and disease is increasingly appreciated. We studied composition microbial communities present blood across 192 individuals, including healthy controls patients with three disorders affecting brain: schizophrenia, amyotrophic lateral sclerosis bipolar disorder. By using high quality unmapped RNA sequencing reads as candidate reads, we performed profiling transcripts detected whole blood. were able to detect a wide range bacterial archaeal...
ABSTRACT Heterozygous variants in the glucocerebrosidase ( GBA ) gene are common and potent risk factors for Parkinson’s disease (PD). also causes autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, emerging evidence from human genetics implicates many other LSD genes PD susceptibility. We have systemically tested 88 conserved fly homologs of 38 requirements aging adult Drosophila brain potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn),...
Bipolar disorder (BD) is a highly heritable mood with complex genetic architecture and poorly understood etiology. We performed whole blood transcriptome analysis in BD case-control sample (Nsubjects = 480) by RNA sequencing. While we observed widespread differential gene expression patterns between affected unaffected individuals, these effects were largely linked to lithium treatment at the time of draw (FDR < 0.05, Ngenes 976) rather than diagnosis itself 6). These lithium-associated...