The second messenger cAMP plays a pivotal role in the regulation of many biological processes in the heart, including calcium dynamics, contraction, and gene transcription. With an increasing number of hormones that stimulate cAMP production as well as the identification of a multitude of targets for cAMP-mediated pathways, an intriguing yet complicated question is how specificity of signaling is ensured? In other words, how does a particular hormone regulate a specific phosphorylation event when it acts via a common second messenger? The identification of scaffolding proteins that link upstream activators with their downstream targets has provided a molecular framework that allows for compartmentation of cAMP signaling pathways as well as the orchestration of spatial-temporal control over phosphorylation events.

A-Kinase Anchoring Proteins (AKAPs) are prototypical examples of scaffolding proteins that direct cAMP-responsive events while coordinating the activity of multiple signaling enzymes. AKAPs bind the regulatory subunit of the cAMP-dependent protein kinase and localize the enzyme to discrete locations within the cell. Additionally, AKAPs coordinate multiple signaling pathways through the anchoring of additional signaling enzymes such as phosphatases, phosphodiesterases, and other kinases.

My research focus is the understanding of how the specific subcellular localization of signaling enzymes regulates cardiac physiology. In particular, we have characterized a scaffolding protein termed mAKAP and demonstrated its association with several signaling enzymes including the protein phosphatase PP2A, the phosphodiesterase PDE4D3, the cAMP-dependent protein kinase PKA, the Big Map Kinase ERK5, and the transcription factor MEF2D. Furthermore, we have demonstrated how association with the complex regulates the activities of ERK5, PDE4D3 and PP2A. We are now investigating the contribution of these mAKAP-bound enzymes for the induction of cardiac hypertrophy.

Accepting Lab Rotation Students: Spring 2 Block 2025

Lab Rotation Projects
The research focus of the Dodge-Kafka laboratory is the understanding of how the specific subcellular localization of signaling enzymes regulates cardiac physiology and induction of cardiac disease. We use a variety of techniques including luciferase assays, kinase/phosphodiesterase/phosphatase assays, transfections, DNA manipulation, construction of adenoviral vectors, co-immunoprecipitations, signal cell siRNA, site-directed mutagenesis, and primary cell culture. Rotations in the lab include:

--Examining the molecular mechanisms that activate the transcription factors involved in the induction of cardiac disease
--Molecular characterization of AKAP signaling complexes
--Determining the molecular architecture of cAMP signaling domains in the heart

Other projects available and can be discussed depending on student’s interests.

Journal Articles

Letters

Reviews