Kimberly LeBlanc
A5029402519- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Neurogenetic and Muscular Disorders Research
- MicroRNA in disease regulation
- Retinal Development and Disorders
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Osteoarthritis Treatment and Mechanisms
- Muscle Physiology and Disorders
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Lysosomal Storage Disorders Research
- Genetic and Kidney Cyst Diseases
- Genetic Neurodegenerative Diseases
- Cardiovascular Effects of Exercise
- Genetic factors in colorectal cancer
- Wnt/β-catenin signaling in development and cancer
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
Harvard University
2018-2024
Baylor College of Medicine
2023
University of Washington
2023
CooperSurgical (United States)
2023
University of California System
2022
The Coordinating Center
2021
Columbia University
2021
University of Massachusetts Chan Medical School
2005-2014
University of Utah
2012
Hebrew University of Jerusalem
2012
Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved two decades. Driving the lack therapeutic inroads, molecular etiology osteosarcoma elusive. MicroRNAs (miRNAs) demonstrated far-reaching effects on cellular biology development cancer. Their role osteosarcomagenesis largely unexplored. Here we identify for first time an miRNA signature reflecting pathogenesis from surgically procured samples human patients. The...
Multiple microRNAs (miRNAs) that target the osteogenic Runt-related transcription factor 2 (RUNX2) define an interrelated network of miRNAs control osteoblastogenesis. We addressed whether these have functional targets beyond RUNX2 coregulate skeletal development. Here, we find seven RUNX2-targeting (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-205, and miR-217) also regulate chondrogenic GATA tricho-rhino-phalangeal syndrome I (TRPS1). Although efficacy each miRNA to or TRPS1 differs...
Borrelia burgdorferi, the agent of Lyme disease, causes a multisystemic illness that can affect skin, heart, joints, and nervous system is capable attachment to diverse cell types. Among host components recognized by this spirochete are fibronectin glycosaminoglycans (GAGs). Three surface-localized GAG-binding bacterial ligands, Bgp, DbpA, DbpB, have been previously identified, but recent studies suggested at least one additional ligand expressed on spirochetal surface when adapted mammalian...
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...
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 "diagnostic odyssey" is well known and described in genetic counseling literature. Studies addressing the psychological, emotional, financial costs of not having a diagnosis have shown how it permeates lives patients families. Undiagnosed Diseases Network aims to end this odyssey by providing diagnoses individuals with undiagnosed conditions through multidisciplinary evaluations, whole exome genome sequencing, basic science research. It also provides an opportunity learn from families...
Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 functions, by examining expression cartilage during mouse human osteoarthritis (OA) progression response to mechanical loading. Spared diseased compartments knees of OA patients mice with surgical destabilization medial meniscus were examined for changes mRNA (Q‐PCR) protein (immunoblot, immunohistochemistry). levels quantified static compression bovine...
Abstract Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition affects fewer than 200,000 individuals. However, there an estimated 7000 diseases, and 25–30 million Americans in total (7.6–9.2% of population 2018) affected such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for with disease. Mass spectrometry-based metabolomics lipidomics...
Nascent proteins destined for the cell membrane and secretory pathway are targeted to endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing protein TMEM208, is one of three pathways that facilitates translocation nascent into ER. in vivo function this ill characterized multicellular organisms. Here, we generated a CRISPR-induced null allele fruit fly ortholog CG8320/Tmem208 by replacing gene with Kozak-GAL4 sequence. We show...
Abstract The burden of living with an undiagnosed condition is high and includes physical emotional suffering, frustrations, uncertainty. For patients families experiencing these stressors, higher levels empowerment may be associated better outcomes. Thus, it important to understand the experiences conditions their affected by in order identify strategies for fostering empowerment. In this study, we used Genetic Counseling Outcome Scale (GCOS‐24) assess support group participation 35 adult...
Abstract Introduction The Undiagnosed Diseases Network (UDN), a clinical research study funded by the National Institutes of Health, aims to provide answers for patients with undiagnosed conditions and generate knowledge about underlying disease mechanisms. UDN evaluations involve collaboration between clinicians researchers go beyond what is possible in settings. While medical outcomes have been explored, this first formal assessment patient caregiver experience. Methods We invited...
Genetic results have implications not only for the individual, but also their family members. Research on communication of genetic has primarily focused families affected by adult-onset, dominant conditions as well more common such familial hypercholesterolemia, cardiomyopathies, and hearing loss. This study therefore aimed to characterize result in with rare undiagnosed identify factors that influence communication. One hundred forty-two individuals who received a diagnosis from Undiagnosed...
Abstract Objective When studying any specific rare disease, heterogeneity and scarcity of affected individuals has historically hindered investigators from discerning on what to focus understand diagnose a disease. New nongenomic methodologies must be developed that identify similarities in seemingly dissimilar conditions. Materials Methods This observational study analyzes 1042 patients the Undiagnosed Diseases Network (2015-2019), multicenter, nationwide research using phenotypic data...
Although clinician, researcher, and patient resources for matchmaking exist, finding similar patients remains an obstacle rare disease diagnosis. The goals of this study were to develop test the effectiveness Internet case-finding strategy identify factors associated with increased matching within a population.
The Runx family of transcription factors supports cell fate determination, cycle regulation, global protein synthesis control, and genetic as well epigenetic regulation target genes. Runx1, which is essential for hematopoiesis; Runx2, required osteoblast differentiation; Runx3, involved in neurologic gut development; are expressed the growth plate during chondrocyte maturation, chondrocytes permanent cartilage structures. While Runx2 known to control genes that contribute hypertrophy,...