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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.


 

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
Funded by K2M, Inc.

This project seeks to identify biological pathways that are important for the development idiopathic scoliosis. We are performing RNA sequencing (RNA-Seq) on vertebral bone, bone marrow aspirate, and cells isolated from blood of idiopathic scoliosis patients, and cells isolated from blood of matched controls. The mRNA transcriptome profiles will be compared between patients with idiopathic scoliosis and matched controls, with the goal of discovering novel RNA biomarkers for idiopathic scoliosis. These biomarkers could serve as prognostic indicators of the type, severity, and risk of curvature progression for patients. Overall, understanding the transcriptome profiles of tissues relevant to idiopathic scoliosis will provide insight into the disease pathogenesis.

 
Transcriptome Profiling of Progressive Idiopathic Scoliosis via mRNA Sequencing Funded by Fondation Cotrel – Institut de France

The primary goal of this project is to utilize RNA sequencing (RNA-Seq) technology to identify differences in the transcriptomes of cells isolated from blood of pre-adolescent individuals affected with idiopathic scoliosis and matched controls. 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 idiopathic scoliosis transcriptome.

Musculoskeletal 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. Dr. Miller and Dr. Baschal have recently embarked on the creation of a biobank of tissue samples from patients with musculoskeletal diseases or injuries. This biobank will allow us to further understand orthopedic diseases and injuries, with the eventual goal of improving patient care. This is a collaborative project across the Department of Orthopedics.

 

Funding

National Institutes of Health (NIH)/
National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS)

K2M

Fondation Cotrel – Institut de France

Children’s Hospital Colorado

University of Colorado School of Medicine

 

Collaborations

 

Ken Jones, PhD (Department of Pediatrics, University of Colorado Anschutz Medical Campus)

Lee Niswander, PhD (Department of Pediatrics, University of Colorado Boulder)

Bruce Appel, PhD (Department of Pediatrics, University of Colorado Anschutz Medical Campus)

Chad Pearson, PhD (Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus)

Matthew Taylor, PhD (Department of Cardiology, University of Colorado Anschutz Medical Campus)

Christina Gurnett, MD, PhD and Matt Dobbs, MD (Washington University in St. Louis)

Alec Wilson, PhD and Cristina Justice, PhD (National Human Genome Research Institute)