Thomas McDonald, MD

Professor, Internal Medicine (Cardiology) and Molecular Pharmacology & Physiology

Member

Professor, College of Medicine Molecular Pharmacology & Physiology

Professor, College of Medicine Internal Medicine

Contact Info

• 560 Channelside Drive
  Tampa FL 33602
• Academic Email: thomasmcdonald@usf.edu
• Academic Phone: (813) 974-5413
• View My C.V. | View My Website

Education

Biography

Dr. McDonald is a Physician-Scientist in the Departments of Medicine (Cardiology) and Molecular Pharmacology & Physiology at USF Morsani College of Medicine. His research and clinical activities focus on Mendelian genetic cardiac conditions of arrhythmia and cardiomyopathy. Aligned with the McDonald laboratory is the USF Cardiogenetics Clinic where families are evaluated for hereditary heart diseases. Blood samples from clinic patients are collected for re-programming into patient-specific-induced Pluripotent Stem Cells (iPSCs). The iPSCs are differentiated into a variety of tissue types, including cardiac myocytes and other cardiac-resident cell types. When cultured together, “Cardiac Organoids” are generated to study the interplay of different cell lineages that comprise the intact human heart. This functional tissue, with the identical genetic constitution of the donor can recapitulate the biological processes underlying their condition and have been termed “disease-in-a-dish”. Using patient-specific iPSCs, the McDonald laboratory investigates the precise mechanisms of how genetic variation causes disease particular to the patient. These disease mechanisms are further explored by employing specific therapeutic modalities with the aim towards translational approaches and Precision Medicine.

Academic Philosophy

Interdisciplinary and Emerging Signature Programs

• Cardiovascular
• Cardiovascular Sciences
• Cellular and Molecular Biology
• Neurodegenerative Disease

Memberships

• Member (Heart Rhythm Society, 2007 - Present)
• Member (American Society of Biochemistry and Molecular Biology, 2002 - Present)
• Member (Biophysical Society, 1997 - Present)
• Fellow (American Heart Association, 1992 - Present)

Recent Publications

• Muller RD McDonald T Pope K Cragun . Evaluation of Clinical Practices Related to Variants of Uncertain Significance Results in Inherited Cardiac Arrhythmia and Inherited Cardiomyopathy Genes Circulation: Genomic and Precision Medicine. : 13, 2020.
• Chen J Liu Z Creagh J Zheng R McDonald . Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits AM J Physiol Heart Circ Physiol. , 2019.
• Bertalovitz AC, Osterbur Badhey ML, McDonald TV. Synonymous nucleotide modification of the KCNH2 gene affects both mRNA characteristics and translation of the encoded hERG ion channel. The Journal of biological chemistry. , 2018.
• Musunuru K, Bernstein D, Cole FS, Khokha MK, Lee FS, Lin S, McDonald TV, Moskowitz IP, Quertermous T, Sankaran VG, Schwartz DA, Silverman EK, Zhou X, Hasan AAK, Luo XJ. Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research. Circulation. Genomic and precision medicine. 11(4) : e002178, 2018.
• Bertalovitz A Osterbur Badhey M McDonald . Synonymous Nucleotide modification of the KCNH2 gene affects both mRNA characteristics and translation of the encoded hERG ion channel Journal of Biological Chemistry. , 2018.
• Gando I, Morganstein J, Jana K, McDonald TV, Tang Y, Coetzee WA. Infant sudden death: Mutations responsible for impaired Nav1.5 channel trafficking and function. Pacing and clinical electrophysiology : PACE. 40(6) : 703-712, 2017.
• Josephs K, Patel K, Janson CM, Montagna C, McDonald TV. Compound heterozygous CASQ2 mutations and long-term course of catecholaminergic polymorphic ventricular tachycardia. Molecular genetics & genomic medicine. 5(6) : 788-794, 2017.
• Monyak RE, Emerson D, Schoenfeld BP, Zheng X, Chambers DB, Rosenfelt C, Langer S, Hinchey P, Choi CH, McDonald TV, Bolduc FV, Sehgal A, McBride SMJ, Jongens TA. Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model. Molecular psychiatry. 22(8) : 1140-1148, 2017.
• Osterbur Badhey ML, Bertalovitz AC, McDonald TV. Express with caution: Epitope tags and cDNA variants effects on hERG channel trafficking, half-life and function. Journal of cardiovascular electrophysiology. 28(9) : 1070-1082, 2017.
• Lin Y, Williams N, Wang D, Coetzee W, Zhou B, Eng LS, Um SY, Bao R, Devinsky O, McDonald TV, Sampson BA, Tang Y. Applying High-Resolution Variant Classification to Cardiac Arrhythmogenic Gene Testing in a Demographically Diverse Cohort of Sudden Unexplained Deaths. Circulation. Cardiovascular genetics. 10(6) , 2017.
• Choi CH, Schoenfeld BP, Bell AJ, Hinchey J, Rosenfelt C, Gertner MJ, Campbell SR, Emerson D, Hinchey P, Kollaros M, Ferrick NJ, Chambers DB, Langer S, Sust S, Malik A, Terlizzi AM, Liebelt DA, Ferreiro D, Sharma A, Koenigsberg E, Choi RJ, Louneva N, Arnold SE, Featherstone RE, Siegel SJ, Zukin RS, McDonald TV, Bolduc FV, Jongens TA, McBride SM. Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models. Frontiers in behavioral neuroscience. 10: 703-712, 2016.
• Osterbur ML, Zheng R, Marion R, Walsh C, McDonald TV. An Interdomain KCNH2 Mutation Produces an Intermediate Long QT Syndrome. Human mutation. 36(8) : 764-73, 2015.
• Choi CH, Schoenfeld BP, Weisz ED, Bell AJ, Chambers DB, Hinchey J, Choi RJ, Hinchey P, Kollaros M, Gertner MJ, Ferrick NJ, Terlizzi AM, Yohn N, Koenigsberg E, Liebelt DA, Zukin RS, Woo NH, Tranfaglia MR, Louneva N, Arnold SE, Siegel SJ, Bolduc FV, McDonald TV, Jongens TA, McBride SM. PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(1) : 396-408, 2015.
• Delio M, Patel K, Maslov A, Marion RW, McDonald TV, Cadoff EM, Golden A, Greally JM, Vijg J, Morrow B, Montagna C. Development of a Targeted Multi-Disorder High-Throughput Sequencing Assay for the Effective Identification of Disease-Causing Variants. PloS one. 10(7) : 1140-1148, 2015.
• Erskine KE, Hidayatallah NZ, Walsh CA, McDonald TV, Cohen L, Marion RW, Dolan SM. Motivation to pursue genetic testing in individuals with a personal or family history of cardiac events or sudden cardiac death. Journal of genetic counseling. 23(5) : 849-59, 2014.
• Wang D, Shah KR, Um SY, Eng LS, Zhou B, Lin Y, Mitchell AA, Nicaj L, Prinz M, McDonald TV, Sampson BA, Tang Y. Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths. Forensic science international. 237: 90-9, 2014.
• Sroubek J, Krishnan Y, McDonald TV. Sequence and structure-specific elements of HERG mRNA determine channel synthesis and trafficking efficiency. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27(8) : 3039-53, 2013.
• Schoenfeld BP, Choi RJ, Choi CH, Terlizzi AM, Hinchey P, Kollaros M, Ferrick NJ, Koenigsberg E, Ferreiro D, Leibelt DA, Siegel SJ, Bell AJ, McDonald TV, Jongens TA, McBride SM. The Drosophila DmGluRA is required for social interaction and memory. Frontiers in pharmacology. 4: 90-9, 2013.
• Linder J, Hidayatallah N, Stolerman M, McDonald TV, Marion R, Walsh C, Dolan S. Perceptions of an implantable cardioverter-defibrillator: A qualitative study of families with a history of sudden life-threatening cardiac events and recommendations to improve care. The Einstein journal of biology and medicine : EJBM. 29(1-2) : 3039-53, 2013.
• Krishnan Y, Zheng R, Walsh C, Tang Y, McDonald TV. Partially dominant mutant channel defect corresponding with intermediate LQT2 phenotype. Pacing and clinical electrophysiology : PACE. 35(1) : 3-16, 2012.
• Sroubek J, Krishnan Y, Chinai J, Buhl S, Scharff MD, McDonald TV. The use of Bcl-2 over-expression to stabilize hybridomas specific to the HERG potassium channel. Journal of immunological methods. 375(1-2) : 215-22, 2012.
• Krishnan Y, Li Y, Zheng R, Kanda V, McDonald TV. Mechanisms underlying the protein-kinase mediated regulation of the HERG potassium channel synthesis. Biochimica et biophysica acta. 1823(8) : 1273-84, 2012.
• Chen J, Angeletti R, McDonald TV, Xiao H. Binding interface of cardiac potassium channel proteins identified by hydrogen deuterium exchange of synthetic peptides. Analytical and bioanalytical chemistry. 403(5) : 1303-9, 2012.
• Sroubek J, McDonald TV. Protein kinase A activity at the endoplasmic reticulum surface is responsible for augmentation of human ether-a-go-go-related gene product (HERG). The Journal of biological chemistry. 286(24) : 21927-36, 2011.
• Chen J, Weber M, Um SY, Walsh CA, Tang Y, McDonald TV. A dual mechanism for I(Ks) current reduction by the pathogenic mutation KCNQ1-S277L. Pacing and clinical electrophysiology : PACE. 34(12) : 1652-64, 2011.
• Choi CH, Schoenfeld BP, Bell AJ, Hinchey P, Kollaros M, Gertner MJ, Woo NH, Tranfaglia MR, Bear MF, Zukin RS, McDonald TV, Jongens TA, McBride SM. Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain research. 1380: 106-19, 2011.
• Zheng R, Thompson K, Obeng-Gyimah E, Alessi D, Chen J, Cheng H, McDonald TV. Analysis of the interactions between the C-terminal cytoplasmic domains of KCNQ1 and KCNE1 channel subunits. The Biochemical journal. 428(1) : 75-84, 2010.
• Choi CH, McBride SM, Schoenfeld BP, Liebelt DA, Ferreiro D, Ferrick NJ, Hinchey P, Kollaros M, Rudominer RL, Terlizzi AM, Koenigsberg E, Wang Y, Sumida A, Nguyen HT, Bell AJ, McDonald TV, Jongens TA. Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue. Biogerontology. 11(3) : 347-62, 2010.
• Govorunova EG, Moussaif M, Kullyev A, Nguyen KC, McDonald TV, Hall DH, Sze JY. A homolog of FHM2 is involved in modulation of excitatory neurotransmission by serotonin in C. elegans. PloS one. 5(4) : e10368, 2010.
• Chen J, Chen K, Sroubek J, Wu ZY, Thomas D, Bian JS, McDonald TV. Post-transcriptional control of human ether-a-go-go-related gene potassium channel protein by alpha-adrenergic receptor stimulation. Molecular pharmacology. 78(2) : 186-97, 2010.
• Ren XQ, Liu GX, Organ-Darling LE, Zheng R, Roder K, Jindal HK, Centracchio J, McDonald TV, Koren G. Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines. American journal of physiology. Heart and circulatory physiology. 299(5) : H1525-34, 2010.
• McBride SM, Choi CH, Schoenfeld BP, Bell AJ, Liebelt DA, Ferreiro D, Choi RJ, Hinchey P, Kollaros M, Terlizzi AM, Ferrick NJ, Koenigsberg E, Rudominer RL, Sumida A, Chiorean S, Siwicki KK, Nguyen HT, Fortini ME, McDonald TV, Jongens TA. Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(28) : 9510-22, 2010.
• Chen J, Sroubek J, Krishnan Y, Li Y, Bian J, McDonald TV. PKA phosphorylation of HERG protein regulates the rate of channel synthesis. American journal of physiology. Heart and circulatory physiology. 296(5) : H1244-54, 2009.
• Chen J, Zheng R, Melman YF, McDonald TV. Functional interactions between KCNE1 C-terminus and the KCNQ1 channel. PloS one. 4(4) : 347-62, 2009.
• Waller KL, McBride SM, Kim K, McDonald TV. Characterization of two putative potassium channels in Plasmodium falciparum. Malaria journal. 7: 19, 2008.
• Li Y, Sroubek J, Krishnan Y, McDonald TV. A-kinase anchoring protein targeting of protein kinase A and regulation of HERG channels. The Journal of membrane biology. 223(2) : 107-16, 2008.
• Wu ZY, Chen K, Haendler B, McDonald TV, Bian JS. Stimulation of N-terminal truncated isoform of androgen receptor stabilizes human ether-á-go-go-related gene-encoded potassium channel protein via activation of extracellular signal regulated kinase 1/2. Endocrinology. 149(10) : 5061-9, 2008.
• Waller KL, Kim K, McDonald TV. Plasmodium falciparum: growth response to potassium channel blocking compounds. Experimental parasitology. 120(3) : 280-5, 2008.
• Um SY, McDonald TV. Differential association between HERG and KCNE1 or KCNE2. PloS one. 2(9) : e933, 2007.
• deSouza N, Cui J, Dura M, McDonald TV, Marks AR. A function for tyrosine phosphorylation of type 1 inositol 1,4,5-trisphosphate receptor in lymphocyte activation. The Journal of cell biology. 179(5) : 923-34, 2007.
• Bian JS, McDonald TV. Phosphatidylinositol 4,5-bisphosphate interactions with the HERG K(+) channel. Pflugers Archiv : European journal of physiology. 455(1) : 105-13, 2007.
• Li Y, Um SY, McDonald TV. Voltage-gated potassium channels: regulation by accessory subunits. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. 12(3) : 199-210, 2006.
• Ghosh K, Cappiello CD, McBride SM, Occi JL, Cali A, Takvorian PM, McDonald TV, Weiss LM. Functional characterization of a putative aquaporin from Encephalitozoon cuniculi, a microsporidia pathogenic to humans. International journal for parasitology. 36(1) : 57-62, 2006.
• Burgos Angulo M, Bertalovitz A, Argenziano MA, Yang J, Patel A, Zesiewicz T, McDonald, TV Frataxin Deficiency Alters Gene Expression in Friedreich Ataxia Derived IPSC-Neurons and Cardiomyocytes. Mol Genet Genomic Med. PMID: 36369844(0) , 2022.
• Yang J, Burgos Angulo M, Argenziano MA, Bertalovitz A, Beidokhti MN, McDonald TV Phenotypic Variability in iPSC-induced Cardiomyocytes and Cardiac Fibroblasts Carrying Diverse LMNA Mutations. Frontiers in Physiology, section Cardiac Electrophysiology. 143:106137, 2021.
• Yang J, Samal E, Burgos Angulo M, Bertalovitz A, McDonald TV Generation of an arrhythmogenic right ventricular cardiomyopathy derived iPSC cell line (USFi004-A) carrying a heterozygous mutation in PKP2 (c.1799delA). Stem Cell Res,. PMID: 34034221, 2021.
• Angulo Burgos M, Yang J, Argenziano MA, Bertalovitz A, Beidokhti MN, McDonald T Generation of a Friedreich’s Ataxia patient-derived iPSC line USFi001-A Stem Cell Research. PMID: 34034220, 2021.
• Argenziano MA, Burgos Angulo M, Beidokhti MN, Yang J, Bertalovitz AC, McDonald TV . Generation of a heterozygous FLNC mutation-carrying human iPSC line, USFi002-A, for modeling dilated cardiomyopathy Stem Cell Research. PMID: 34088019, 2021.
• Najari Beidokhti M, Bertalovitz A, Ji W, McCormack J, Jefferies L, Sempou E, Khokha MK, McDonald TV*, Lakhani SA*. Functional testing for variant prioritization in a family with Long QT syndrome Mol Genet Genomics. PMID: 33876311, 2021.
• Siskind T, Williams N, Sebastin M, Marion R, McDonald TV, Walsh C, Sampson B, Tang Y, Clark BC. Genetic screening of relatives of decedents experiencing sudden unexpected death: medical examiner's office referrals to a multi-disciplinary cardiogenetics program. Journal of Community Genetics. PMID: 36203036, 2022.
• Chidipi B, Angulo MB, Shah SI, Rieser M, Ullah G, McDonald TV, Noujaim SF The dynamin-related protein 1 is decreased and the mitochondrial network is altered in Friedreich's ataxia cardiomyopathy. International Journal of Cell Biology. PMID: 34923139, 2022.