Thomas V. McDonald, M.D.
Areas of Investigation
The focus of Dr. Thomas McDonald’s laboratory is the role of ion channel function in normal and disease states.
Ion channels are involved in cellular excitability and signal transduction in every cell type of every organism. Using a multidisciplinary approach that includes molecular and cellular biology, biochemistry, electrophysiology and human genetics, the McDonald laboratory studies a variety of aspects of ion channel structure, function, and regulation.
Mutations in several genes (HERG, KCNQ1, KCNE1, KCNE2) affecting cardiac potassium channels can cause sudden death in the inherited long QT syndrome. Moreover, altered expression and regulation of channels may underlie “electrical remodeling” in common acquired heart diseases. The McDonald group is investigating how these channels are regulated by phosphorylation and through interactions with other proteins (Kagan et al. EMBO J, 2002. 21: 1889-1898; Melman et al. Neuron, 2004. 42: 927-937; Um et al. PLoS-ONE, 2007. 2: e933).
- Second messenger regulation of channel function
- Post-translational modifications that alter synthesis, assembly and trafficking of channels
- Effects of commonly used cardiovascular drugs on channels
- How disease-causing mutations alter channel function by perturbing protein structures.
In association with the above efforts, Dr. McDonald helped create a clinic dedicated to the genetic analysis and treatment of survivors of sudden cardiac death and their families. The resulting studies are likely to reveal new arrhythmia-associated mutations, which will be characterized at molecular, cellular, and electrophysiological levels.
- Role of potassium channels in the infectivity and virulence of T. cruzi, the most common cause of dilated cardiomyopathy in Brazil