The Roden Lab has a strong tradition of translating research
from the bedside to the bench and back again.
The overarching theme of research in the Roden laboratory is how genomic variation affects variability in disease susceptibility and response to drug treatment.
Principal Initiatives of the Roden Lab
Dr. Dan Roden has been Principal Investigator for Vanderbilt’s large BioVU resource that links DNA samples from almost 300,000 patients to their deidentified EHRs since the program was launched in 2007.
The lab has a strong tradition in translating discovery from the bedside to the bench and back.
The eMERGE network’s long-term goal is to understand how best to implement genomic discovery to enable “Genomic Medicine”, the idea that genomic information will be used to guide individual treatments.
The All of Us initiative aims to recruit at least 1,000,000 Americans, including those not usually represented in biomedical research.
The protocol for an ongoing project could implement the following methodology.
Celular Initiatives
The availability of genetic sequencing is changing clinical management for patients with genetic arrhythmia syndromes and their families. However, a major barrier to the widespread application of sequencing to practice is that the function of the vast majority of variants that we discover have never been seen or studied before, so we don’t actually know their function. Dr. Roden is co-Principal Investigator in the large CardioVar consortium that aims to use novel high-throughput functional approaches to determine pathogenicity of nearly all missense variants in key arrhythmia genes, as well as other genes important for cardiac function.
A common experiment in the lab has been to study function of genetic variants in key ion channels controlling cardiac electrical behavior, often discovered in the Genetic Arrhythmia Clinic where Dr. Roden sees patients. The conventional approach has been to compare mutant and wild-type function using heterologous expression, but the lab has in the last decade turned increasingly to human cardiac cells derived from induced pluripotent stem cells. This model has the advantage that it allows the study of how individual genetic changes affect overall cellular function, and can be especially powerful when combined with DNA editing. Experiments are conducted using conventional patch-clamping as well as newer automated approaches that allow simultaneous study of up to 384 cells.
One-third of human adults will develop atrial fibrillation (AF) in their lifetimes. Atrial Fibrillation causes burdensome symptoms, stroke, and increased mortality, but for the past 20 years we have not had truly important changes in treatment or prognosis. We need new approaches. Many factors, such as aging, diabetes, high blood pressure, or having an affected family member, increase AF risk. But not everyone with AF has all these risk factors and some have none.
The Roden lab has discovered specific molecules generated by inflammation that cause atrial tissue damage and increase AF risk. Our Center will build on these findings to test how inflammation contributes to AF risk across all patients, and test a new therapy designed to prevent the tissue damage leading to AF.
Population Project (Roden lab): Identifying AF subtypes driven by inflammation: While atrial fibrillation is a very common problem, it comes in many 'flavors': some patients have incapacitating symptoms and others have none. Some patients have many recognized risk factors, others have none. Some patients respond well to certain drugs, others don't.
Our goal in the Population Project is to use advanced computer-based techniques to identify subgroups of patients with AF in whom specific risk factors are causing AF, or in whom specific treatments 'like the anti-inflammatory approaches being developed in other Projects at this Center may be especially effective. In this work, we will build a large collection of patients with and without AF so other groups can work with us to answer other questions related to AF, its treatment, and its outcomes.
