Summary of Current Research

We are interested in the fundamental mechanisms of cellular signaling. A deep, quantitative description of the behavior and interactions of the components of signaling systems is crucial to an understanding of cellular physiology, and the roles of cells in higher order systems. The time is ripe for a rigorous investigation of signaling. Armed with an increasing knowledge of the molecules involved in signaling processes, we are now developing highly-specific probes, sensors and other tools to study the behavior of these molecules in their native settings and the interactions that give rise to the richness of cellular function.

Much of our work centers on signaling by the intracellular second messengers cAMP and cGMP. These small molecule messengers regulate a huge variety of processes, including cellular excitability, learning, memory, vision, olfaction, development, fertilization, heart rate, blood pressure, and metabolism. In cell physiology experiments, we are developing sensors to decipher the signals carried by these two messengers. An exciting finding with this approach in several cell types is that cAMP is generated at high concentrations in diffusionally-restricted microdomains near the surface membrane. These microdomains allow for efficient and selective activation of protein kinases and other downstream effector proteins. In chemical biology and biophysical experiments, we are developing potent and specific activators and inhibitors of ion channels, as well as other proteins, in order to understand how they participate in cell signaling. The strategies we are using require only limited structural information and should lead to promising drug candidates.

Recent Publications

See PubMed link above. 

Education

• Ph.D. 1985, Cornell University
• M.S. 1982, Cornell University
• B.A. 1979, University of Pennsylvania

Previous Positions

University of Colorado Health Sciences Center 1990-2002

Postdoctoral Fellow, Stanford University School of Medicine 1985-1990 

Preceptor Rotations

Faculty Mentorship

Dr. Karpen might be available as a mentor for 2010-2011.

Dr. Karpen might be available as a mentor for 2009-2010.