Harold A. Singer, PhD
Areas of Study
- University of Virginia School of Medicine1982PhD
- SUNY Binghamton1975BS
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.
- vascular biology
- regulation of vascular smooth muscle (VSM) function
- Ca2+/calmodulin-dependent protein kinase II (CaMKII)
- vascular remodeling in response to injury/disease
Saddouk F, Sun L-Y, Liu Y-F, Jiang M, Singer DV, Backs J, Van Riper D, Ginnan R, Schwarz JJ, Singer HA. Ca2+/Calmodulin-dependent Protein Kinase II-γ (CaMKIIγ) negatively regulates vascular smooth muscle cell proliferation and vascular remodeling. FASEB J, 30(3):1051-64, 2016. PMID:26567004
Spinelli AM, Liu Y-F, Sun L-Y Gonzalez-Cabos JC, Backs J, Trebak M, Singer HA. Smooth Muscle CaMKIIδ Promotes Allergen Induced Airway Hyperresponsiveness and Inflammation. Pflügers Archiv - European Journal of Physiology, 467(12):2541-3554,2015. PMID:26089028
Liu Y, Sun L-Y, Singer DV, Ginnan R, Singer HA. CaMKIIδ-dependent inhibition of cAMP- response element-binding protein activity in vascular smooth muscle. J Biol. Chem, 288(47):33519-29, 2013. PMID: 24106266. PMC3837101
Ginnan R, Zou X, Pfleiderer PJ, Mercure MZ, Barroso M, and Singer HA. Vascular smooth muscle cell motility is mediated by a physical and functional interaction of Ca2+/calmodulin-dependent protein kinase IIδ2 and Fyn. J.Biol. Chem . 288(41):29703-12, 2013.PMID: 24003228. PMC3795267
View Harold A. Singer's articles on the National Institute of Health's PubMed website.