Who does this work?

People

Principal Investigator

Brett Kroncke, Ph.D.
Assistant Professor of Medicine
Vanderbilt Center for Arrhythmia Research and Therapeutics (VanCART)
Vanderbilt University Medical Center
Department of Pharmacology, Vanderbilt University
Center for Structural Biology
Vanderbilt Genomics Institute
Data Science Institute
1225E MRBIV
2215B Garland Ave.
Nashville, TN 37232
Email: brett.kroncke@gmail.com
Research: My long-term research interests are to explain the interplay between membrane protein flexibility and structure that lead to robust function and dysfunction involved in human disease, with a special emphasis on the ion channels involved in the heart contraction cycle. My goal is to develop ion channel-specific predictive algorithms—leveraging sequence, structural, and phenotype data—capable of accurately predicting the phenotype of any point mutation within these molecules. Given the high estimated frequency of cardiac ion channel mutation carriers, estimated at ~4% of the general population, the driving force of this project is not only to provide a reliable estimate of if a variant is pathogenic, but also if a variant is not pathogenic. For my graduate work at the University of Virginia, I focused on experimental methods development for determining membrane protein flexibility and membrane protein structure. As a Postdoctoral Fellow at Vanderbilt, I further pursued translational opportunities of experimental and computational structural biology. The last two years of my training focused on learning from experts in the fields of cardiac arrhythmia genetics, and computational phenotype-predictive modeling to construct predictive models of ion channel phenotypes and validate the resulting predictions.

Postdoctoral Fellows

Rizwan Ullah, Ph.D. Kroncke Lab from 2019 - to present
1215 MRBIV
2215B Garland Ave.
Nashville, TN 37232
Email: rizwan.ullah@vumc.org
Research: Dr. Ullah did his Ph.D. in Zoology from Aligarh Muslim University, completed in 2019. In his doctoral work, he successfully characterized cathepsin L protein, a cysteine protease from the liver fluke Fasciola gigantica, and additionally identified therapeutic molecules for the control of these parasites. Rizwan also used cathepsin L protein as a diagnostic antigen to detect field infections.


Research Assistants

Loren Vanags
1215 MRBIV
2215B Garland Ave.
Nashville, TN 37232
Email: loren.r.vanags@vumc.org
Research: Since joining our team in 2018, Loren has been an indispensable asset to the lab, playing a crucial role in the establishment of our wet-lab facilities and the advancement of our research on genetic determinants of heart arrhythmias. Her expertise in CRISPR-Cas9 editing of induced pluripotent stem cells (iPSCs) has been pivotal in characterizing genetic variants associated with heart arrhythmias. Loren has also spearheaded the development and validation of functional assays for the RYR2 gene in both HEK293 cells and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Loren is responsible for running all fluorescence-activated cell sorting (FACS) experiments, enhancing our lab's capabilities in cellular analysis. Her efforts were instrumental in generating the most comprehensive map of variant effects for the cardiac potassium channel gene KCNH2, marking a significant milestone in cardiovascular genetics research. Loren's dedication and multifaceted contributions have not only been integral to our lab's success but have also positioned us at the forefront of innovative research in cardiac arrhythmias.

Devyn Mitchell
1215 MRBIV
2215B Garland Ave.
Nashville, TN 37232
Email: devyn.w.mitchell@vumc.org
Research: Since joining the lab in June 2019, Devyn has become a key contributor to our cutting-edge research on the genetic underpinnings of heart arrhythmias, focusing on the high-throughput experimental characterization of KCNH2 variants. His work involves heterologous expression in HEK cells and endogenous expression studies in SH-SY5Y cells, providing critical insights into variant functionality. Devyn's initiative enabled our lab to pivot to using induced pluripotent stem cells (iPSCs) as a research model, demonstrating exceptional skill in reprogramming PBMCs to hiPSCs, a technique that has broadened our experimental scope and potential for discovery. He routinely leads the characterization of these cells, particularly differentiated cardiomyocytes, employing the Nanion CardioExcyte96 for detailed functional analysis. Devyn's contributions are instrumental in advancing our understanding of cardiac arrhythmias and enhancing our lab's capabilities in cellular modeling and genetic analysis.

Former Lab Members

Krystian Kozek, Ph.D. Kroncke Lab from 2018-2019
1215 MRBIV
2215B Garland Ave.
Nashville, TN 37232
Email: krystian.a.kozek.1@vumc.org
Research: Krystian completed his Ph.D. in the lab of David Weaver in the Department of Pharmacology, Vanderbilt University in 2018. His focus was on modulation of GIRK channels by small molecules. In the Kroncke lab he worked on refining methods for high-throughput characterization of missense mutations in the cardiac potassium channel Kv11.1 (gene KCNH2/hERG).