Joel B. Krier
A5074558971- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Congenital heart defects research
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Biomedical Text Mining and Ontologies
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cellular transport and secretion
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Prenatal Screening and Diagnostics
- Diet and metabolism studies
- ATP Synthase and ATPases Research
- Ion Channels and Receptors
- Cancer-related gene regulation
- Cardiomyopathy and Myosin Studies
- Blood disorders and treatments
- Genetic Syndromes and Imprinting
Harvard University
2015-2024
Brigham and Women's Hospital
2014-2023
IIT@Harvard
2020-2021
Boston Children's Hospital
2019-2021
Massachusetts General Hospital
2005-2021
MGH Institute of Health Professions
2020
Mass General Brigham
2017
VA Boston Healthcare System
2017
Oregon Health & Science University
2017
Geisinger Health System
2017
There are few better examples of the need for data sharing than in rare disease community, where patients, physicians, and researchers must search "the needle a haystack" to uncover rare, novel causes within genome. Impeding pace discovery has been existence many small siloed datasets individual research or clinical laboratory databases and/or disease-specific organizations, hoping serendipitous occasions when two distant investigators happen learn they have phenotype common can "match"...
Significance The mechanical integrity of the arterial wall is dependent on a properly structured ECM. Elastin and collagen are key structural components ECM, contributing to stability elasticity normal arteries. Lysyl oxidase (LOX) normally cross-links elastin molecules in process forming proper fibers elastic lamellae. Here, using whole-genome sequencing humans genome engineering mice, we show that missense mutation LOX causes aortic aneurysm dissection because insufficient cross-linking...
The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. "BabySeq Project" a randomized trial that explores medical, behavioral, and economic impacts integrating into care healthy sick newborns.Families newborns are enrolled from Boston Children's Hospital Brigham Women's nurseries, half to receive report includes monogenic disease variants, recessive carrier variants childhood onset or actionable disorders, pharmacogenomic variants. All families...
Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on and outcomes of adding WGS to standardized family history assessment primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566) Setting: Academic practices. Participants: 9 physicians (PCPs) 100 generally healthy patients recruited at ages 40 65 years. Intervention: Patients were randomly assigned...
Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, decision-making remains largely unstudied. It also unknown how best to communicate results physicians patients improve health. We describe the design of MedSeq Project: first randomized trials WGS care. This pair controlled compares standard care two contexts: (a) disease-specific genomic medicine a cardiomyopathy clinic (b) general...
Abstract Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at presentation, evolving through a caudocranial pattern into generalized dystonia, prominent oromandibular, laryngeal cervical involvement. Although KMT2B-related is emerging as one the most common causes early-onset genetic much remains to be understood about full spectrum disease. We describe cohort...
The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into medicine. To facilitate return results potential medical relevance physicians and patients participating in Project, we sought develop reporting approach for effective communication such findings.Genome was performed on Illumina HiSeq platform. Variants were filtered, interpreted, validated according methods developed by Laboratory Molecular Medicine consistent...
The development of massively parallel sequencing (or next-generation sequencing) has facilitated a rapid implementation genomic in clinical medicine. Genomic (GS) is now an essential tool for evaluating rare disorders, identifying therapeutic targets neoplasms, and screening prenatal aneuploidy. Emerging applications, such as GS preconception carrier predisposition healthy individuals, are being explored research settings utilized by members the public eager to incorporate information into...
Abstract Background Despite growing evidence of diagnostic yield and clinical utility whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost reimbursement barriers limiting access to such testing. The resulting actions WES for who previously faced insurance coverage have not yet been explored. Methods We performed a retrospective descriptive analysis outcomes facing prior subsequently enrolled the Undiagnosed Diseases Network (UDN). Clinical was...
Over 100 million research participants around the world have had array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these been offered return actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed results from 36,417 in Mass General Brigham Biobank to confirm pathogenic likely variants (PLPVs) 59 genes. Variant verification prior participant recontact revealed that GT falsely identified PLPVs 44.9% samples, failed identify 72.0% detected...
<h3>Importance</h3> Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families. <h3>Objective</h3> To assess of nGS families from BabySeq Project, a randomized clinical trial evaluating care newborns well-baby nurseries and intensive units. <h3>Design, Setting, Participants</h3> In this conducted May 14, 2015, to 21, 2019, at units 3 Boston, Massachusetts,...
Abstract Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they abundant myelin membranes. Serine palmitoyltransferase, enzyme that catalyses rate-limiting reaction sphingolipid synthesis, is composed multiple subunits including an activating subunit, SPTSSA. both essential cytotoxic their synthesis must therefore be tightly regulated. Key to homeostatic regulation ORMDL proteins bound serine...