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Miller Lab Research


Lab Goals

 
The Miller scoliosis lab is at a critical meeting point between clinical research and basic science. We utilize clinical specimens (maybe from you!) to achieve our goal of broadening the scientific community’s knowledge of the complex molecular underpinnings, including the genetics, of idiopathic scoliosis. Our research includes analysis of the DNA and RNA of hundreds of clinical specimens collected over decades, and we believe understanding this condition fully at the molecular level may one day lead to new detection, prevention, and treatment options for the estimated ~2% of the worldwide population with IS.
 
Please see the “Projects” tab for more information on our specific projects.
 

Current Projects

 
Exome Sequencing in Families with Idiopathic Scoliosis
National Institutes of Health
R01AR068292
7/1/2015-6/30/2020
 
Our NIH R01 focuses on performing exome sequencing (the ~1-2% of the genome that codes for proteins) on up to 100 samples from our cohort of scoliosis families in an effort to discover variants suspected of causing the disease. We will carefully select affected and unaffected individuals from our pedigrees for the most statistical, genetic, and clinical relevance. After analysis, we will perform functional studies of the identified variants and genes suspected of causing IS in a zebrafish model using CRISPR technologies, in collaboration with Dr. Bruce Appel’s lab.
 
Please see our official grant details on the NIH Reporter website


Search for Biomarkers in Idiopathic Scoliosis
K2M
 
Using a combination of bone, bone marrow, and osteoblasts derived from blood samples of IS patients undergoing spinal surgeries, we will perform RNA-sequencing on each tissue and compare to the osteoblast transcriptomes of matched patient controls. This study aims to discover novel mRNA biomarkers for IS, which could serve as prognostic indicators of the type, severity, and risk of curvature progression for patients.
 
Biobank
 
Biobanks are collections of biological materials used for research purposes, which may be shared with a certain scientific community to further their own research. The Miller scoliosis lab has recently embarked on the creation of a biobank out of hundreds (###?) of patient DNA samples, which can be shared among collaborators who are also investigating IS (in accordance with COMIRB rules and each participant’s informed consent).
 
Cotrel
 
This project focuses on performing RNA-sequencing on sorted osteoblast progenitor cells from the blood of 8 adolescents with IS and 8 age and clinically-matched controls without IS. With this data we hope to identify novel transcripts, isoforms, splice sites, and/or sequence frequency differences between the two populations in an effort to profile the IS transcriptome.
 

Past Projects

 
Funding

NIH/NIAMS
K2M
Fondation Cotrel – Institut de France
Children’s Hospital Colorado 
University of Colorado School of Medicine
 

Collaborators

 
Ken Jones (Department of Pediatrics, University of Colorado Anschutz Medical Campus)
Lee Niswander (Department of Pediatrics, University of Colorado Anschutz Medical Campus)
Bruce Appel (Department of Pediatrics, University of Colorado Anschutz Medical Campus)
Christina Gurnett and Matt Dobbs (Washington University)
Alec Wilson and Cristina Justice (NHGRI)