Stephen C. Cannon, MD, PhD is a Professor in the Department of Physiology in the David Geffen School of Medicine at UCLA. He received both a B.S and an M.S. in Mechanical Engineering at Washington University in St. Louis in 1980. His master’s thesis explored how increased muscle stiffness and intensity of the stretch reflex with mechanical loading produces an instability that may cause tremor. Upon graduation, he entered the Medical Scientists Training Program at Johns Hopkins where he worked with Prof. David Robinson to identify the locus of the brainstem neural integrator for the oculomotor system and demonstrated how lateral inhibition is a critical neural network feature of this premotor circuit. He completed a medical internship and neurology residency at Massachusetts Hospital, where he was chief resident in 1990. Dr. Cannon then completed a research postdoctoral fellowship in David Corey’s lab, where he made a fundamental discovery of the sodium channel defect that causes susceptibility to periodic paralysis. Based on this new work on channelopathies of muscle, he started a lab in the neurobiology department at Harvard Medical School where he was on the faculty until 2002 when he moved to UT Southwestern Medical Center in Dallas as Chair of Neurology. In 2010, he became Associate Dean for Undergraduate Medical Education and developed a combined BA/MD training program with UT Dallas. In 2015, Dr. Cannon was recruited to UCLA as the Chair of Physiology in the David Geffen School of Medicine.
Research Interests: Ion channelopathies of skeletal muscle
The primary research interests of our laboratory are how ion channels regulate the electrical excitability of cells and how defects in these channels lead to human disease. In the past two decades, mutations of ion channel genes have been found to be the primary cause for over 100 human diseases. The focus of our laboratory has been to understand the mechanistic basis for a group of inherited disorders of skeletal muscle caused by mutations of voltage-gated ion channels. The derangements in electrical excitability of affected muscle may cause involuntary after-contractions (excess excitability called myotonia) or transient episodes of severe weakness (temporary loss of excitability called periodic paralysis). Our lab studies the consequences of mutations on channel function, uses computational models of muscle excitability to explore the impact of altered channel behavior, and developed genetically-engineered mouse models to gain insights on the pathomechanisms of these disorders and to test pre-clinical strategies for therapeutics and disease modification.
This work has led to the discovery of gain-of-function defects in the NaV1.4 sodium channel that cause a predisposition to myotonia, to periodic paralysis, or to both and thereby provides a mechanistic basis for the genotype-phenotype associations in the allelic disorders hyperkalemic periodic paralysis, paramyotonia congenita, and sodium channel myotonia. More recent work shows that loss-of-function changes for NaV1.4 may cause pseudo-myasthenia or congenital myopathy. We also established the gating pore “leak” resulting from mutations in the voltage-sensor domain of NaV1.4 or CaV1.1 as a major determinant in causing susceptibility to hypokalemic periodic paralysis due to paradoxical depolarization in low K+. Our knock-in mutant mouse models prove these missense mutations are sufficient to cause myotonia or periodic paralysis, have yielded new insights on the mechanisms for triggering attacks, and provided proof-of-principle that inhibitors of the Na-K-2Cl transporter can reverse or prevent acute attacks of weakness in hypokalemic periodic paralysis. Our latest projects are exploring the mechanism by which vigorous exercise is a trigger for eliciting attacks of weakness in periodic paralysis.
Honors and Awards
- 2022 Biophysical Society Award in the Biophysics of Health and Disease
- 2019 Paul Horowicz Endowed Lecture - Univ Rochester
- 2014 Regents Outstanding Teaching Award, University of Texas
- 2012 Patricia A. Smith Distinguished Chair in Neuromuscular Disease, UT Southwestern
- 2009 MERIT Award, NIH
- 2002 Linda and Mitch Hart Distinguished Chair in Neurology
- 2000 Derek Denny-Brown Neurological Scholar Award, American Academy of Neurology
- 1995 Esther and Joseph Klingenstein Fellowship
- 1992 Alfred P. Sloan Fellowship
- 1991 HHMI Postdoctoral Fellowship for Physicians
- 1990 Charles A Dana Fellowship
- 1990 Chief Resident in Neurology, Massachusetts General Hospital
- 1984 Michael A Shanoff Award, Johns Hopkins School of Medicine
- 1980 summa cum laude, B.S. Mechanical Engineering Washington University
- 1976 Alexander S. Langsdorf Fellowship, Washington University (St. Louis)