Title: Faculty & research interests

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Robert S Kass
Robert S Kass, PhD
Alumni and Hosack Professor and Chair of Pharmacology
Vice Dean for Research

Full Member

Department: Pharmacology

P&S 2-401
212-305-3720
rsk20@columbia.edu


Personal Website

Disease Models: Cardiovascular Diseases, Congenital Disorders

Stem Cell Categories: iPS

Model Organisms: Human

Themes: , Bioengineering

Our laboratory has a long-standing interest in the relationship between the structure and function of ion channel proteins. One focus of the laboratory is the understanding of the mechanistic basis and therapeutic management of congenital channelopathies. This a group of pathologies due to inherited mutations in genes coding for ion channels and/or ion channel-associated proteins. Channelopathies are widespread ranging from inhetied epileptic syndromes to diabetes to cardiac arrhythmias. Our laboratory has focused on heritable cardiac rhythm disturbances in general and the Long QT syndrome in particular. The Long QT syndrome (LQTS), a rare (1:2500 to 1:10,000) inherited disorder associated with an increased propensity to arrhythmogenic syncope, polymorphous ventricular tachycardia, and sudden cardiac death, has provided a wealth of information about fundamental mechanisms underlying human cardiac electrophysiology that has come about because of true collaborative interactions between clinical and basic scientists. Our understanding of the mechanisms that determine the critical plateau and repolarization phases of the human ventricular action potential have been raised to new levels through these studies with impact on the manner in which potassium channels; sodium channels; and channel-associated proteins regulate this critical period of electrical activity. It is clear that there are distinct risk factors associated with the different LQTS genotypes, and building on collaboration between clinical and basic science teams our laboratory has developed mutation-specific therapeutic approaches to manage this disorder in a gene- dependent manner. Most studies to date have relied upon determining the functional consequence of inherited mutations on channel function and pharmacology using heterologous expression systems such as HEK 293 cells. Most recently the laboratory has begun investigations of mutant channel activity in cardiac myocytes derived from inducible pluripotent stems cells, cells that have unique and powerful potential to provide a personalized approach to management of this and other heritable rhythm disorders. These approaches will provide, for the first time, direct testing of potential therapeutic agents in the specific genetic background of the patient presenting with the disease phenotype.



Publications:

Osteen, J.D., Gonzalez, C., Sampson, K.J., Iyer, V., Rebolledo, S., Larsson, H.P., andKass, R.S.(2010)
KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate. Proc Natl Acad Sci U S A 107(52):22710-5. (2010)

Osteen, J.D., Sampson, K.J., & Kass, R.S. (2010)
The cardiac IKs channel, complex indeed. Proc Natl Acad Sci U S A 107(44):18751-52. (2010)

Terrenoire, C., Houslay, M.D., Baillie, G.S., & Kass, R.S. (2009)
The cardiac IKS potassium channel macromolecular complex includes the phosphodiesterase PDE4D3. J Biol Chem 284(14):9140-6. (2009)

Chung, D.Y., Chan, P.J., Bankston, J.R., Yang, L., Liu, G., Marx, S.O, Karlin, A.,and Kass, R.S.(2009)
Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines. Proc Natl Acad Sci U S A 106(3):743-48. (2009)

Bankston J.R., Yue, M., Chung, W., Spyres, M., Pass, R.H, Silver, E., Sampson, K.J., and Kass, R.S. (2007)
A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response. PLoS One 2(12):e1258. (2007)

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