Andrew B. Crouse
A5090790767- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- COVID-19 Clinical Research Studies
- Neurogenetic and Muscular Disorders Research
- Congenital heart defects research
- Lysosomal Storage Disorders Research
- Global Cancer Incidence and Screening
- Diabetes and associated disorders
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Economic and Financial Impacts of Cancer
- Endoplasmic Reticulum Stress and Disease
- Genomic variations and chromosomal abnormalities
- Retinal Development and Disorders
- RNA modifications and cancer
- Neurological disorders and treatments
- Protein Tyrosine Phosphatases
- Genetics, Aging, and Longevity in Model Organisms
- Metabolism and Genetic Disorders
- Sepsis Diagnosis and Treatment
- Ion channel regulation and function
University of Alabama at Birmingham
2003-2025
University of California System
2022
The Coordinating Center
2021
University of Alabama
2021
Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches lower mortality lacking.
Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic luminal residues the TLR chaperone protein UNC93B1, which identified both negative positive regulatory regions affecting TLR3, TLR7, TLR9 responses. We subsequently two families harboring...
There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, number of disease diagnoses will continue increase, resulting need for novel treatment options. Identifying treatments these disorders is challenging due a limited understanding mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive develop new treatments. A promising avenue drug...
Abstract Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating a large cohort inpatients with COVID-19 and correlated the subpopulation frequencies clinical outcomes. Using blood, show increased systemic circulation COVID-19, identify validate S100A8/A9 as defining marker megakaryocyte dysfunction. We further reveal S100A8/A9+ contain acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein...
ABSTRACT BACKGROUND Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches lower mortality lacking. METHODS We conducted retrospective electronic health record data analysis 25,326 subjects tested for COVID-19 between 2/25/20 6/22/20 at University Alabama Birmingham Hospital, tertiary...
With one in ten suffering from of 10,000 rare diseases, precision medicine opens a path toward identifying therapies for patients. Conversely, it is patients—through their collective experience and the knowledge captured genetics—who open common For much human history, patients diseases have found themselves beyond hope. an estimated roughly known diseases,1Haendel M. Vasilevsky N. Unni D. Bologa C. Harris Rehm H. Hamosh A. Baynam G. Groza T. McMurry J. et al.How many are there?.Nat. Rev....
The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult discern. Understanding these mechanisms is critical for developing treatments address underlying causes of diseases rather than merely presenting symptoms. Moreover, same dysfunctional series interrelated implicated in recessive may also lead milder potentially preventable carriers general population. Seizures a common phenotype can result from diverse...
ABSTRACT MAPK8IP3- related neurodevelopmental disorders are a spectrum of rare conditions caused by de novo mutations in the MAPK8IP3 gene that encodes JIP3 protein. These associated with symptoms manifest children and cause brain abnormalities, profound intellectual disabilities, movement disorders, developmental delays. is required for axonal transport proteins organelles between soma synaptic terminal neurons, process critical normal development function. Homozygous loss-of-function lead...
This report explores a therapeutic hypothesis for addressing the potential effects of loss-of-function variant in MAPK8IP3 gene. We describe pediatric male with developmental delay associated an early truncation . genetic alteration is suspected to reduce levels functional JIP3 protein (encoded by gene), potentially contributing manifestations, including hypotonia, gait imbalance, frequent falls, and motor incoordination. hypothesize that increasing expression may mitigate patient’s symptoms...
Genomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although computational tools incorporated into diagnostic workflows this task are continually evolving improving, we nevertheless sought investigate commonalities across processing reveal consensus standard practice highlight exploratory analyses where technical theoretical method improvements would most impactful.
The Rab family of guanosine triphosphatases (GTPases) includes key regulators intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that highly expressed brain. Through exome sequencing international matchmaking platforms, we identified five de novo...
PurposeGrowth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with dominant human disease in family variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum variants document nature variants.MethodsWe present cohort six probands de novo nonsense/frameshift (4/6 patients) missense (2/6) GDF11. We generated gdf11 mutant zebrafish...
Abstract Autophagy regulates the degradation of damaged organelles and protein aggregates, is critical for neuronal development, homeostasis, maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families a disorder characterized by speech motor impairment, similar facial characteristics. Rare, conserved, bi-allelic were identified ATG4D , one four ATG4...
Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence DPH5 as novel cause of embryonic lethality profound neurodevelopmental delays (NDDs).Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) created p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays DPH5-knockout human yeast...
We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability autism spectrum disorder who carry heterozygous missense variants PRKAR1B gene, which encodes R1β subunit cyclic AMP-dependent protein kinase A (PKA).
DROSHA encodes a ribonuclease that is subunit of the Microprocessor complex and involved in first step microRNA (miRNA) biogenesis. To date, has not yet been associated with Mendelian disease. Here, we describe two individuals profound intellectual disability, epilepsy, white matter atrophy, microcephaly dysmorphic features, who carry damaging de novo heterozygous variants DROSHA. constrained for missense moderately intolerant to loss-of-function (o/e = 0.24). The loss fruit fly ortholog...
Abstract The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families heterozygous, de novo truncating in the last exon of DAGLA neuro-ocular phenotype characterized by developmental delay, ataxia complex oculomotor abnormality. All displayed paroxysms nystagmus or eye deviation accompanied...
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to sheer number and complexity sources. In addition, semantic incompatibilities hinder efforts harmonize integrate across these diverse As part The Biomedical Translator Consortium, we developed graph-based question-answering system designed augment human reasoning accelerate translational scientific discovery: system. We applied answer biomedical questions in...
The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic severe disease COVID-19 in humans. While efforts quickly identify effective antiviral therapies have focused largely on repurposing existing drugs 1-4 , current standard care, remdesivir, remains only authorized intervention and provides modest clinical benefits 5 . Here we show that water-soluble derivatives α-tocopherol potent activity synergize with remdesivir as inhibitors SARS-CoV-2 RNA-dependent RNA...
The "diagnostic odyssey" describes the process those with undiagnosed conditions undergo to identify a diagnosis. Throughout this process, families of children have multiple opportunities decide whether continue or stop their search for diagnosis and accept lack diagnostic label. Previous studies identified factors motivating family begin searching, but there is limited information about decision-making in prolonged how affected child impacts family's decision. This study aimed understand...
This year marks the 63rd anniversary of International Society Nephrology, which signaled nephrology's emergence as a modern medical discipline. In this article, we briefly trace course history to show clear arc in its evolution—of increasing resolution nephrological data—an that is converging with computational capabilities enable precision nephrology. general, medicine refers tailoring treatment individual characteristics patients. For an operational definition, takes form optimization,...