Melissa R. Miller
A5054974974- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Genetic Associations and Epidemiology
- Liver Disease Diagnosis and Treatment
- Genomics and Rare Diseases
- Ion channel regulation and function
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Ion Channels and Receptors
- Cystic Fibrosis Research Advances
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Bioinformatics and Genomic Networks
- Neurobiology and Insect Physiology Research
- RNA Interference and Gene Delivery
- BRCA gene mutations in cancer
- Pharmaceutical Economics and Policy
- Neonatal Respiratory Health Research
- Pancreatic function and diabetes
- Cancer Genomics and Diagnostics
- Health Systems, Economic Evaluations, Quality of Life
- Computational Drug Discovery Methods
- Diet, Metabolism, and Disease
- Reproductive biology and impacts on aquatic species
- Epigenetics and DNA Methylation
- Cannabis and Cannabinoid Research
Pfizer (United States)
2017-2025
Northeastern University
2024
Columbia University
2023
University of California, Berkeley
2014-2021
University of Helsinki
2020
Institute for Molecular Medicine Finland
2020
Target (United States)
2018
Johns Hopkins University
2009-2017
High Throughput Biology (United States)
2011-2017
Hospital for Sick Children
2013-2015
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide detailed summary this initiative, including technical and biological validations, insights into disease signatures, prediction modelling for various demographic health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping 2,923 proteins that identifies 14,287 primary genetic associations,...
Steroids regulate cell proliferation, tissue development, and signaling via two pathways: a nuclear receptor mechanism genome-independent signaling. Sperm activation, egg maturation, steroid-induced anesthesia are executed the latter pathway, key components of which remain unknown. Here, we present characterization human sperm progesterone that is conveyed by orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show ABHD2 highly expressed in spermatozoa, binds progesterone,...
This study aimed to investigate the value of imaging-based multivariable body composition profiling by describing its association with coronary heart disease (CHD), type 2 diabetes (T2D), and metabolic health on individual population levels.The first 6,021 participants scanned UK Biobank were included. Body profiles (BCPs) calculated, including abdominal subcutaneous adipose tissue, visceral tissue (VAT), thigh muscle volume, liver fat, fat infiltration (MFI), determined using magnetic...
Abstract The UK Biobank Pharma Proteomics Project (UKB-PPP) is a collaboration between the (UKB) and thirteen biopharmaceutical companies characterising plasma proteomic profiles of 54,306 UKB participants. Here, we describe results from first phase UKB-PPP, including protein quantitative trait loci (pQTL) mapping 1,463 proteins that identifies 10,248 primary genetic associations, which 85% are newly discovered. We also identify independent secondary associations in 92% cis 29% trans loci,...
Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories these data seek to be disease-agnostic therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is public resource datasets genomic annotations dedicated type diabetes (T2D) related traits. Here, we make the T2DKP more accessible prospective users useful existing users. First, evaluate T2DKP's comprehensiveness by comparing its with...
Significance The calcium channel of sperm—CatSper—is vital for male fertility. CatSper is activated by the hormone progesterone, but its pharmacological profile not well studied. By exploring steroid selectivity activation, we found one additional agonist—pregnenolone sulfate—and two plant-derived inhibitors pristimerin and lupeol. averting sperm hyperactivation, both can prevent fertilization, thus acting as contraceptive agents. Additionally, regulation endogenous steroids, explain why...
A major hindrance to evaluating nematode populations for anthelmintic resistance, as well screening existing drugs, new compounds, or bioactive plant extracts properties, is the lack of an efficient, objective, and reproducible in vitro assay that adaptable multiple life stages parasite genera. To address this need we have developed "Worminator" system, which objectively quantitatively measures motility microscopic parasitic nematodes. The system built around computer application...
Background Cow's milk intake has been inconsistently associated with islet autoimmunity (IA) and type 1 diabetes (T1D) development. Genetic environmental factors may modify the effect of cow's on IA T1D risk. Methods The Diabetes Autoimmunity Study in Young (DAISY) follows children at increased risk (presence autoantibodies to insulin, GAD65, or IA-2 twice succession) We examined 1835 DAISY data intake: 143 developed IA, 40 subsequently T1D. protein lactose were calculated from prospectively...
STUDY QUESTIONAre significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility if so what is their functional significance for fertilization success?
Circulating immunoreactive trypsinogen (IRT), a biomarker of exocrine pancreatic disease in cystic fibrosis (CF), is elevated most CF newborns. In those with severe transmembrane conductance regulator (CFTR) genotypes, IRT declines rapidly the first years life, reflecting progressive damage. Consistent this progression, less newborn measure would reflect more disease, including compromised islet compartments, and potentially increased risk CF-related diabetes (CFRD). We show two independent...
Ion channels control sperm navigation within the female reproductive tract and, thus, are critical for their ability to find and fertilize an egg. The flagellar calcium channel CatSper controls hyperactivated motility is dependent on alkaline cytoplasmic pH. latter accomplished by either proton transporters or, in human sperm, via voltage-gated Hv1. To provide concerted regulation, ion regulatory proteins must be compartmentalized. Here, we describe nanodomains comprised of Hv1, CatSper, its...
Abstract The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a unique private/public partnership between the and eight biopharma companies that will sequence exomes of all ∼500,000 participants. Here we describe early results from exome data generated by this consortium for first ∼200,000 UKB subjects key features project enabled UKB-ESC to come together generate data. sequencing 200,643 enrollees are now accessible research community. Approximately 10M variants were observed within...
During transit through the female reproductive tract, mammalian spermatozoa are exposed to increasing concentrations of progesterone (P4) released by cumulus oophorus. P4 triggers massive calcium influx into human sperm activation sperm-specific channel CatSper. These properties thought be unique since CatSper is not sensitive in rodent sperm. Here, performing patch clamp recording from rhesus macaque for first time, we report that they express P4-sensitive identically and react inducing...
Does a man (patient 1) with previously described deficiency in principle cation channel of sperm (CatSper) function have mutation the CatSper-epsilon (CATSPERE) and/or CatSper-zeta (CATSPERZ) gene?Patient 1 has homozygous in-frame 6-bp deletion exon 18 (c.2393_2398delCTATGG, rs761237686) CATSPERE.CatSper is principal calcium mammalian spermatozoa. Spermatozoa from patient had specific loss CatSper and were unable to fertilize at IVF. Loss could not be attributed genetic abnormalities coding...
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists available for functional examination of these Using a cell-based high throughput screening approach, lead compound with the pyrazolopyrimidine skeleton was identified as TRPC6 agonist. Synthetic schemes its analogues were established, structural–activity relationship studies carried out....
Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed profile miRNAs comprehensively at all NAFLD stages.