Harold A. Singer, PhD

The principal objective of my laboratory is to understand mechanisms by which intracellular Ca²⁺ signals regulate vascular smooth muscle (VSM) function, physiologically and in vascular disease.  Ongoing work has focused on the structure and function of one ubiquitous Ca²⁺ signal mediator, namely multifunctional Ca²⁺/calmodulin-dependent protein kinase II (CaMKII).  One major aspect of our current effort is to use molecular/genetic approaches to manipulate CaMKII isozyme expression in order to test the concept that Ca²⁺ signaling, via specific CaMKII isoforms, regulates VSM gene transcription and VSM phenotype-specific functions.  Through collaborations, we are evaluating pro-inflammatory signaling pathways and molecules in VSM that contribute to vascular remodeling in response to injury and aortic aneurysmal disease.  More recently, we have broadened our investigations of CaMKII-dependent functions to bring new insights into control of vascular wall remodeling by evaluating function of CaMKII isozymes in vascular endothelium; specifically in the contexts of re-endothelialization following intraluminal arterial injury, arteriovenous fistula maturation and failure, and angiogenesis.

We have established ourselves as one of the laboratories leading this field and have available a unique combination of expertise and reagents in smooth muscle biology, Ca²⁺ signaling and CaMKII structure-function that we bring to studies of vascular biology and pathophysiology and which we have made widely available to colleagues in the field.

Summary:

- vascular biology
- regulation of vascular smooth muscle (VSM) function
- Ca²⁺-signaling
- Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)
- vascular remodeling in response to injury/disease