The Roden Lab has a strong tradition of translating research
from the bedside to the bench and back again.
The overarching theme of our research is how genomic variation affects variability in disease susceptibility and response to drug treatment.
Our focus at the bench is on abnormalities of cardiac rhythm, and individual projects incorporate the expertise of the laboratory in mining electronic health records (EHRs) and in basic electrophysiologic methods, including the use of emerging medium and high-throughput approaches for functional genomics.
Principal Investigator Dr. Dan Roden is a leading researcher in pharmacogenomics and personalized medicine. In addition to the active projects listed below, he directed Vanderbilt’s site in the NIH’s Pharmacogenetics Research Network (PGRN) and the American Heart Association’s Strategically Focused Atrial Fibrillation Research Network (AF-SFRN).
Principal Clinical Initiatives
BioVU
Dr. Roden has been Principal Investigator for Vanderbilt’s large BioVU resource that links DNA samples from more than 300,000 patients to their deidentified EHRs since the program was launched in 2007.
eMerge
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.
Dr. Roden has served as Vanderbilt site PI for eMERGE since the network started in 2007.
All of Us
The All of Us initiative aims to recruit at least 1,000,000 Americans, including those not usually represented in biomedical research.
Dr. Roden serves as co-PI of the All of Us Data and Research Center.
Principal Basic and Translational 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.
The basic idea approach is shown here:
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 AF SFRN center is investigating the role of specific molecules generated by inflammation that cause atrial tissue damage and increase AF risk. The Center tests how inflammation contributes to AF risk in patients (in the Population Project) and in mouse models (in the Basic Project), and in the Clinical Project tests a new therapy designed to prevent the tissue damage leading to AF.
Population Project: 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.