Melina Ellis
A5077077632- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Gastrointestinal motility and disorders
- Parkinson's Disease Mechanisms and Treatments
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- Infant Health and Development
- CRISPR and Genetic Engineering
- Neuropeptides and Animal Physiology
- Autism Spectrum Disorder Research
- Congenital gastrointestinal and neural anomalies
- Cellular transport and secretion
- RNA regulation and disease
- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Biochemical Analysis and Sensing Techniques
- Trace Elements in Health
- Neurological disorders and treatments
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Gastroesophageal reflux and treatments
- Diet and metabolism studies
Sydney Local Health District
2024-2025
Lipscomb University
2025
Concord Repatriation General Hospital
2018-2025
Anzac Research Institute
2015-2024
The University of Sydney
2021-2024
Polish Academy of Sciences
2020
Ludwig-Maximilians-Universität München
2020
Dr. John T. Macdonald Foundation
2020
Mossakowski Medical Research Institute, Polish Academy of Sciences
2020
The University of Melbourne
2008-2019
Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies performed in just one population at a time. Here we large-scale multi-ancestry meta-analysis of with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals European, East Asian, Latin American African ancestry. In meta-analysis, 78 significant loci, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2,...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
In mature animals, neurons and interstitial cells of Cajal (ICC) are essential for organized intestinal motility. We investigated motility patterns, the roles myenteric ICC (ICC-MP), in duodenum colon developing mice vitro. Spatiotemporal mapping revealed regular contractions that propagated both directions from embryonic day (E)13.5 E14.5 colon. The propagating contractions, which we termed ripples, were unaffected by tetrodotoxin present intestine Ret null mutant mice, lack enteric...
Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations the neuroligin family of synaptic adhesion molecules are implicated autism, however whether they expressed and impact GI function via changes enteric nervous system is unknown. We report symptoms two brothers autism R451C mutation Nlgn3 encoding protein, neuroligin-3. confirm presence array genes murine tract investigate impaired protein expression mice carrying human...
The Monogenic Network of the Global Parkinson's Genetics Program (GP2) aims to create an efficient infrastructure accelerate identification novel genetic causes disease (PD) and improve our understanding already identified causes, such as reduced penetrance variable clinical expressivity known disease-causing variants. We aim perform short- long-read whole-genome sequencing for up 10,000 patients with parkinsonism. Important features this project are global involvement focusing on...
The Global Parkinson's Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic clinical data for use in large-scale analyses to dramatically expand our understanding of architecture PD. This report details workflow cohort integration into complex arm GP2, together with outline monogenic hub a companion paper, provides generalizable blueprint establishing large scale collaborative research consortia.
Peptide YY (PYY) and neuropeptide Y (NPY) activate receptors, targets under consideration as treatments for diarrhoea other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity transit using wild-type, single double peptide knockout mice, comparing responses with those from human colon.Mucosae were pretreated a Y₁ (BIBO3304) Y₂ (BIIE0246) receptor antagonist changes in short-circuit current...
The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central system. Changes ENS are a major cause GI symptoms disease may contribute to reported neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure analyze neural regulation CMMCs ex vivo preparations mouse...
Segmentation is an important process in nutrient mixing and absorption; however, the mechanisms underlying this motility pattern are poorly understood. can be induced by luminal perfusion of fatty acid guinea pig small intestine vitro mimicked serotonin (5-HT) reuptake inhibitor fluoxetine (300 nM) cholecystokinin (CCK). Serotonergic CCK-related nutrient-induced segmentation were investigated using selective 5-HT CCK receptor antagonists on isolated segments luminally perfused with 1 mM...
Many payers and pharmacy benefit managers (PBMs) use step therapy requirements formulary alternatives to reduce prescription spending. The clinical utility ultimate outcomes for patients participating in these programs is an area of needed research. To evaluate medication time access required a or alternative after being prescribed specialty psoriasis (PsO) atopic dermatitis (AD). A single-center, retrospective review data collected from electronic health records the patient management...
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.
We investigated the contribution of genomic data reanalysis to diagnostic yield dystonia patients who remained undiagnosed after prior genome sequencing.
Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale.
To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained in elderly, we performed genetic analysis of 230 patients with axonal and onset ≥35 years.We recruited patients, collected clinical data, conducted whole-exome sequencing (WES; n = 126) MME single-gene (n 104). We further queried WES repositories for variants measured blood levels MME-encoded protein neprilysin.In cohort, overall detection rate assumed...
The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central system. Changes ENS are a major cause GI symptoms disease may contribute to reported neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure analyze neural regulation CMMCs ex vivo preparations mouse...
Biallelic mutations in sorbitol dehydrogenase (SORD) have been recently identified as a common cause of recessive axonal Charcot-Marie-Tooth neuropathy (CMT2). We aimed to assess novel long-read sequencing approach overcome current limitations SORD diagnostics due the SORD2P pseudogene and phasing biallelic disease. conducted screen our Australian whole exome (WES) CMT cohort identify individuals with homozygous or compound heterozygous variants. Individuals detected then underwent...
Abstract Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration axons the peripheral nervous system. A missense mutation (p.R158H) in pyruvate dehydrogenase kinase 3 gene ( PDK3 ) has been identified as genetic cause for an X-linked form CMT (CMTX6) two unrelated families. one four PDK isoenzymes that regulate activity complex (PDC). The balance between kinases (PDKs) phosphatases (PDPs) determines...
Abstract Charcot-Marie-Tooth (CMT) disease is a neuromuscular disorder affecting the peripheral nervous system. The diagnostic yield in demyelinating CMT (CMT1) typically ∼80%–95%, of which at least 60% due to PMP22 gene duplication. remainder CMT1 more genetically heterogeneous. We used whole exome and genome sequencing data included GENESIS database investigate novel causal genes mutations cohort ∼2670 individuals with neuropathy. A recurrent heterozygous missense variant p.Thr1424Met...
Cholera toxin (CT) is well established to produce diarrhoea by producing hyperactivity of the enteric neural circuits that regulate water and electrolyte secretion. Its effects on intestinal motor patterns are less understood. We examined luminal CT activity guinea-pig jejunum in vitro. Segments were cannulated at either end mounted horizontally.Their contractile was video-imaged recordings used construct spatiotemporal maps with (1.25 μg/ml or 12.5 μg/ml) lumen. Both concentrations induced...
ABSTRACT Individuals affected by inherited neuromuscular diseases often present with a specific pattern of muscle weakness, which can guide clinicians in genetic investigations and variant interpretation. Nonetheless, more than 50% cases do not receive diagnosis. Oculopharyngodistal myopathy (OPDM) is an manifesting particular combination ptosis, dysphagia distal weakness. Pathologically it characterised rimmed vacuoles intranuclear inclusions on biopsy. In recent years GCC • CCG repeat...
Abstract Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration lower neurons. There currently 29 reported causative genes and four disease loci implicated in dHMN. Despite high genetic heterogeneity, mutations known account for less than 20% dHMN cases, with identified predominantly being point or indels. We have expanded spectrum identification 1.35 Mb complex structural variation (SV) causing form...