Karsten Peppel, Ph.D.

Contact Dr. Peppel

Center for Translational Medicine
1025 Walnut Street, Suite 311
Philadelphia, PA 19107

(215) 503-9428
(215) 503-5731 fax

Medical School

Residency

Fellowship

Degree
Ph.D. SUNY Albany, NY; Molecular Biology 1990

University Appointment
Associate Professor (2006)

Research and Clinical Interests
The current research in my lab seeks to further our understanding of the role of inflammation in vascular pathology. Specifically, we focus on:
The contributions of the two Tumor Necrosis Factor (TNF) receptors, TNFR1 and TNFR2, to vascular remodeling following injury.
The role of signal transduction cascades downstream of the TNF receptors that regulate growth, survival or apoptosis of cells that participate in the vascular repair response.
The potential efficacy of TNF-inhibitory molecules in attenuating pathophysiological vascular remodeling.
Cross-talk between cytokine and growth factor receptors.

My lab employs different in vivo models of vascular injury as well as in vitro culture of primary cells derived from mice with specific gene deletions to achieve these objectives.

In vivo we study the arterialization of murine inferior vena cava segments surgically grafted into the carotid circulation of recipient mice - a process that mimics venous remodeling following coronary artery bypass grafting in patients.

In vitro we focus on proliferation, migration and activation of regulatory factors and protein kinase cascades downstream of receptor activation.

Publications

Most Recent Peer-reviewed Publications

1. Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration.
2. Tumor necrosis factor receptor-2 signaling attenuates vein graft neointima formation by promoting endothelial recovery
3. Substrate specificities of G protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function
4. Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis
5. Regulation of the platelet-derived growth factor receptor-β by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2
6. The platelet-derived growth factor receptor-β phosphorylates and activates G protein-coupled receptor kinase-2: A mechanism for feedback inhibition
7. Activation of vascular smooth muscle cells by TNF and PDGF: Overlapping and complementary signal transduction mechanisms
8. Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor receptor-1 signaling in graft-intrinsic cells
9. Phosphorylation of the platelet-derived growth factor receptor-β by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na+/H+ exchanger regulatory factor
10. Graft-Extrinsic Cells Predominate in Vein Graft Arterialization
11. The Adaptor Protein β-Arrestin2 Enhances Endocytosis of the Low Density Lipoprotein Receptor
12. Targeting Gβγ signaling to inhibit prostate tumor formation and growth
13. Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes.
14. Phosphorylation of the platelet-derived growth factor receptor-β and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization
15. Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells reduces neointimal hyperplasia
16. Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model
17. Expression of aquaporin-1 in human trabecular meshwork cells: Role in resting cell volume
18. Overexpression of G protein - Coupled receptor kinase-2 in smooth muscle cells attenuates mitogenic signaling via G protein - Coupled and platelet-derived growth factor receptors
19. Enhanced morphine analgesia in mice lacking β-arrestin 2
20. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3

View All Publications