Faculty Appointments
Assistant Professor of Medicine
Education
Ph.D., University of Virginia, Charlottesville, VirginiaB.S., Chemistry, University of Wisconsin, Madison, Wisconsin
Research Description
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 the laboratory is to improve our understanding of the clinical burden of ion channel non-synonymous single nucleotide polymorphisms (nsSNPs) on carriers. I believe predicting protein-specific functional phenotypes accurately of nsSNPs within these genes is the best path to reaching this goal. Our initial focus is on ion channels associated with Long QT Syndrome.
Research Keywords
Genetics, Statistics, Biophysics, and Ion Channels
Publications
Kroncke BM, Yang T, Roden DM. Multiple mechanisms underlie increased cardiac late sodium current. Heart Rhythm [print-electronic]. 2019 Jan 1/21/2019; PMID: 30677491, PII: S1547-5271(19)30031-1, DOI: 10.1016/j.hrthm.2019.01.018, ISSN: 1556-3871.
Kroncke BM, Mendenhall J, Smith DK, Sanders CR, Capra JA, George AL, Blume JD, Meiler J, Roden DM. Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1. Comput Struct Biotechnol J. 2019; 17: 206-14. PMID: 30828412, PMCID: PMC6383132, PII: S2001-0370(18)30270-8, DOI: 10.1016/j.csbj.2019.01.008, ISSN: 2001-0370.
Kroncke BM, Yang T, Kannankeril P, Shoemaker MB, Roden DM. Exploiting ion channel structure to assess rare variant pathogenicity. Heart Rhythm [print-electronic]. 2018 Jun; 15(6): 890-4. PMID: 29330128, PMCID: PMC5984725, PII: S1547-5271(18)30021-3, DOI: 10.1016/j.hrthm.2018.01.021, ISSN: 1556-3871.
Kroncke BM, Glazer AM, Smith DK, Blume JD, Roden DM. SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance. Circ Genom Precis Med. 2018 May; 11(5): e002095. PMID: 29728395, PMCID: PMC5941942, PII: CIRCGEN.118.002095, DOI: 10.1161/CIRCGEN.118.002095, ISSN: 2574-8300.
Johnson CN, Potet F, Thompson MK, Kroncke BM, Glazer AM, Voehler MW, Knollmann BC, George AL, Chazin WJ. A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel. Structure [print-electronic]. 2018 May 5/1/2018; 26(5): 683-694.e3. PMID: 29606593, PMCID: PMC5932218, PII: S0969-2126(18)30085-6, DOI: 10.1016/j.str.2018.03.005, ISSN: 1878-4186.
Li B, Mendenhall JL, Kroncke BM, Taylor KC, Huang H, Smith DK, Vanoye CG, Blume JD, George AL, Sanders CR, Meiler J. Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance. Circ Cardiovasc Genet. 2017 Oct; 10(5): PMID: 29021305, PMCID: PMC5679743, PII: CIRCGENETICS.117.001754, DOI: 10.1161/CIRCGENETICS.117.001754, ISSN: 1942-3268.
Deatherage CL, Lu Z, Kroncke BM, Ma S, Smith JA, Voehler MW, McFeeters RL, Sanders CR. Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains. Sci Adv. 2017 Apr; 3(4): e1602794. PMID: 28439555, PMCID: PMC5389784, PII: 1602794, DOI: 10.1126/sciadv.1602794, ISSN: 2375-2548.
Kroncke BM, Duran AM, Mendenhall JL, Meiler J, Blume JD, Sanders CR. Documentation of an Imperative To Improve Methods for Predicting Membrane Protein Stability. Biochemistry [print-electronic]. 2016 Sep 9/13/2016; 55(36): 5002-9. PMID: 27564391, PMCID: PMC5024705, DOI: 10.1021/acs.biochem.6b00537, ISSN: 1520-4995.
Kroncke BM, Van Horn WD, Smith J, Kang C, Welch RC, Song Y, Nannemann DP, Taylor KC, Sisco NJ, George AL, Meiler J, Vanoye CG, Sanders CR. Structural basis for KCNE3 modulation of potassium recycling in epithelia. Sci Adv. 2016 Sep; 2(9): e1501228. PMID: 27626070, PMCID: PMC5017827, PII: 1501228, DOI: 10.1126/sciadv.1501228, ISSN: 2375-2548.
Sahu ID, Craig AF, Dunagan MM, Troxel KR, Zhang R, Meiberg AG, Harmon CN, McCarrick RM, Kroncke BM, Sanders CR, Lorigan GA. Probing Structural Dynamics and Topology of the KCNE1 Membrane Protein in Lipid Bilayers via Site-Directed Spin Labeling and Electron Paramagnetic Resonance Spectroscopy. Biochemistry [print-electronic]. 2015 Oct 10/20/2015; 54(41): 6402-12. PMID: 26418890, PMCID: PMC4812432, DOI: 10.1021/acs.biochem.5b00505, ISSN: 1520-4995.
Kroncke BM, Vanoye CG, Meiler J, George AL, Sanders CR. Personalized biochemistry and biophysics. Biochemistry [print-electronic]. 2015 Apr 4/28/2015; 54(16): 2551-9. PMID: 25856502, PMCID: PMC4415889, DOI: 10.1021/acs.biochem.5b00189, ISSN: 1520-4995.
Mittendorf KF, Kroncke BM, Meiler J, Sanders CR. The homology model of PMP22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing. Biochemistry [print-electronic]. 2014 Oct 10/7/2014; 53(39): 6139-41. PMID: 25243937, PMCID: PMC4188248, DOI: 10.1021/bi500809t, ISSN: 1520-4995.
Peng D, Kim JH, Kroncke BM, Law CL, Xia Y, Droege KD, Van Horn WD, Vanoye CG, Sanders CR. Purification and structural study of the voltage-sensor domain of the human KCNQ1 potassium ion channel. Biochemistry [print-electronic]. 2014 Apr 4/1/2014; 53(12): 2032-42. PMID: 24606221, PMCID: PMC3977583, DOI: 10.1021/bi500102w, ISSN: 1520-4995.
Schlebach JP, Peng D, Kroncke BM, Mittendorf KF, Narayan M, Carter BD, Sanders CR. Reversible folding of human peripheral myelin protein 22, a tetraspan membrane protein. Biochemistry [print-electronic]. 2013 May 5/14/2013; 52(19): 3229-41. PMID: 23639031, PMCID: PMC3762913, DOI: 10.1021/bi301635f, ISSN: 1520-4995.
Kroncke BM, Mendenhall J, Smith DK, Sanders CR, Capra JA, George AL, Blume JD, Meiler J, Roden DM. Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1. Comput Struct Biotechnol J. 2019; 17: 206-14. PMID: 30828412, PMCID: PMC6383132, PII: S2001-0370(18)30270-8, DOI: 10.1016/j.csbj.2019.01.008, ISSN: 2001-0370.
Kroncke BM, Yang T, Kannankeril P, Shoemaker MB, Roden DM. Exploiting ion channel structure to assess rare variant pathogenicity. Heart Rhythm [print-electronic]. 2018 Jun; 15(6): 890-4. PMID: 29330128, PMCID: PMC5984725, PII: S1547-5271(18)30021-3, DOI: 10.1016/j.hrthm.2018.01.021, ISSN: 1556-3871.
Kroncke BM, Glazer AM, Smith DK, Blume JD, Roden DM. SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance. Circ Genom Precis Med. 2018 May; 11(5): e002095. PMID: 29728395, PMCID: PMC5941942, PII: CIRCGEN.118.002095, DOI: 10.1161/CIRCGEN.118.002095, ISSN: 2574-8300.
Johnson CN, Potet F, Thompson MK, Kroncke BM, Glazer AM, Voehler MW, Knollmann BC, George AL, Chazin WJ. A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel. Structure [print-electronic]. 2018 May 5/1/2018; 26(5): 683-694.e3. PMID: 29606593, PMCID: PMC5932218, PII: S0969-2126(18)30085-6, DOI: 10.1016/j.str.2018.03.005, ISSN: 1878-4186.
Li B, Mendenhall JL, Kroncke BM, Taylor KC, Huang H, Smith DK, Vanoye CG, Blume JD, George AL, Sanders CR, Meiler J. Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance. Circ Cardiovasc Genet. 2017 Oct; 10(5): PMID: 29021305, PMCID: PMC5679743, PII: CIRCGENETICS.117.001754, DOI: 10.1161/CIRCGENETICS.117.001754, ISSN: 1942-3268.
Deatherage CL, Lu Z, Kroncke BM, Ma S, Smith JA, Voehler MW, McFeeters RL, Sanders CR. Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains. Sci Adv. 2017 Apr; 3(4): e1602794. PMID: 28439555, PMCID: PMC5389784, PII: 1602794, DOI: 10.1126/sciadv.1602794, ISSN: 2375-2548.
Kroncke BM, Duran AM, Mendenhall JL, Meiler J, Blume JD, Sanders CR. Documentation of an Imperative To Improve Methods for Predicting Membrane Protein Stability. Biochemistry [print-electronic]. 2016 Sep 9/13/2016; 55(36): 5002-9. PMID: 27564391, PMCID: PMC5024705, DOI: 10.1021/acs.biochem.6b00537, ISSN: 1520-4995.
Kroncke BM, Van Horn WD, Smith J, Kang C, Welch RC, Song Y, Nannemann DP, Taylor KC, Sisco NJ, George AL, Meiler J, Vanoye CG, Sanders CR. Structural basis for KCNE3 modulation of potassium recycling in epithelia. Sci Adv. 2016 Sep; 2(9): e1501228. PMID: 27626070, PMCID: PMC5017827, PII: 1501228, DOI: 10.1126/sciadv.1501228, ISSN: 2375-2548.
Sahu ID, Craig AF, Dunagan MM, Troxel KR, Zhang R, Meiberg AG, Harmon CN, McCarrick RM, Kroncke BM, Sanders CR, Lorigan GA. Probing Structural Dynamics and Topology of the KCNE1 Membrane Protein in Lipid Bilayers via Site-Directed Spin Labeling and Electron Paramagnetic Resonance Spectroscopy. Biochemistry [print-electronic]. 2015 Oct 10/20/2015; 54(41): 6402-12. PMID: 26418890, PMCID: PMC4812432, DOI: 10.1021/acs.biochem.5b00505, ISSN: 1520-4995.
Kroncke BM, Vanoye CG, Meiler J, George AL, Sanders CR. Personalized biochemistry and biophysics. Biochemistry [print-electronic]. 2015 Apr 4/28/2015; 54(16): 2551-9. PMID: 25856502, PMCID: PMC4415889, DOI: 10.1021/acs.biochem.5b00189, ISSN: 1520-4995.
Mittendorf KF, Kroncke BM, Meiler J, Sanders CR. The homology model of PMP22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing. Biochemistry [print-electronic]. 2014 Oct 10/7/2014; 53(39): 6139-41. PMID: 25243937, PMCID: PMC4188248, DOI: 10.1021/bi500809t, ISSN: 1520-4995.
Peng D, Kim JH, Kroncke BM, Law CL, Xia Y, Droege KD, Van Horn WD, Vanoye CG, Sanders CR. Purification and structural study of the voltage-sensor domain of the human KCNQ1 potassium ion channel. Biochemistry [print-electronic]. 2014 Apr 4/1/2014; 53(12): 2032-42. PMID: 24606221, PMCID: PMC3977583, DOI: 10.1021/bi500102w, ISSN: 1520-4995.
Schlebach JP, Peng D, Kroncke BM, Mittendorf KF, Narayan M, Carter BD, Sanders CR. Reversible folding of human peripheral myelin protein 22, a tetraspan membrane protein. Biochemistry [print-electronic]. 2013 May 5/14/2013; 52(19): 3229-41. PMID: 23639031, PMCID: PMC3762913, DOI: 10.1021/bi301635f, ISSN: 1520-4995.