Brett Kroncke, PhD, is an Assistant Professor of Medicine in the Division of Clinical Pharmacology within the Department of Medicine at Vanderbilt University Medical Center.
Dr. Kroncke's research focus has been to explain the interplay between membrane protein flexibility and structure that leads to robust function and dysfunction involved in human disease, with a special emphasis on ion channels involved in the heart contraction cycle. The increasing use of next generation sequencing in the clinical arena is uncovering a large number of variants across all genes, but methods to predict their pathogenicity are not well established. This results in an increasing number of “variants of uncertain significance” (VUSs), a major emerging problem in genomic medicine. Rare variants (mutations) in the cardiac ion channels are implicated in diverse heart diseases, including long QT syndrome (LQTS), short QT syndrome (SQTS), and Brugada syndrome (BrS), but are also common in healthy populations. While multiple algorithms predict whether ion channel variants are deleterious (SIFT, PolyPhen-2, PredSNP, CADD, etc.), too many neutral variants are classified as disease-causing.
The long-term research interest of Dr. Kroncke is to improve the understanding of the clinical burden of ion channel non-synonymous single nucleotide polymorphisms (nsSNPs) on carriers. He believes predicting protein-specific functional phenotypes accurately of nsSNPs within these genes is the best path to reaching this goal, initially focused on ion channels associated with Long QT Syndrome.