Richard J. Bodnar, PhD
Research Assistant Professor of Pathology
Dr. Bodnar is a member of the Section of Laboratory Medicine and the Division of Pathology at the VA Pittsburgh Healthcare System (VAPHS).
Veterans Affairs Medical Center
University Dr. C
9E107 Building 1 (132L-U)
Pittsburgh, PA 15240
Office Telephone: 412-360-3468
Lab Telephone: 412-360-3426
Email Address: firstname.lastname@example.org
The research in Dr. Bodnar's laboratory investigates the regulation of angiogenesis, specifically aiming to identify the resident molecules that can be used to improve the wound healing process and treat diseases resulting from pathological neovascularization. The dysregulation of angiogenesis can lead to a variety of pathological conditions such as diabetic retinopathy, rheumatoid arthritis, endometriosis, pulmonary fibrosis, psoriasis, and also promotes tumor growth. Therefore, the identification of an endogenous inhibitor of angiogenesis that is able to override angiogenic signals will provide novel therapies for the treatment of diseases caused by pathological vascularization.
We are focusing on the ELR-negative chemokines, interferon- inducible protein of 10 kD (IP-10, CXCL10), platelet factor 4 (PF4, CXCL4) Interferon-inducible T-cell alpha chemoattractant (ITAC, IP-9, CXCL11), and monokine induced by interferon- (Mig, CXCL9) that have been observed as having angiostatic properties. However, both their mechanism of action is not understood and what roles they play during tissue repair remain ill-defined. The lab is also investigating the role endothelial cells and angiogenesis play in dermal/epidermal communication during the wound healing process. Lastly, we are interested in understanding the signaling mechanisms involved in vascular maturation and remodeling. For this, our focus is on how communication between pericytes and endothelial cells regulates vessel stabilization and maturation.
The receptor for the ELR-negative chemokines is the CXC receptor 3 (CXCR3). Recently, we were the first to show that activation of CXCR3 inhibits endothelial motility through a PKA mediated pathway. We identified that activation of PKA inhibited m-calpain activity, which is required for VEGF stimulated endothelial migration. Furthermore, we have identified that CXCR3 also plays a significant role in regulating vessel stability. We have found that CXCR3 activation induces vessel destabilization through -calpain cleavage of 3 integrin. The loss of integrin function leads to the dissociation of the endothelial cells from the matrix causing anoikis. Currently, we are investigating the role pericytes play in regulating vascular stability. We have found that pericyte interaction with newly formed vessels causes a destabilization of endothelial cells actively involved in angiogenesis. This destabilization causes newly formed vessels to regression. We have found that pericyte mediated dissociation of newly formed vessels is regulated through activation of CXCR3 expressed on endothelial cells. As the vessels become mature endothelial expression of CXCR3 is lost and are not negatively affected by pericyte recruitment. Our current hypothesis is that pericyte play a role in the dissociation of newly formed vessels and stabilization of mature vessels.
Selected PublicationsView Dr. Bodnar's publications on PubMed
Bodnar RJ., EGF and EGFR: The Yin and Yang in the Treatment of Cutaneous Wounds and Cancer, (2013), Advances in Wound Care, Vol. 2 (1) p. 24-29
Yates CC, Rodgers MG, Jaynes J., Wells A, Bodnar RJ, Turner T.; An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis, (2012) PLoS One; 2012; Vol. 7(7) p. e40812.
Yates CC, Bodnar RJ, Wells A, Matrix control of scaring, (2011) Cell Mol. Life Sci. Vol. 68, p. 1871-1881
Yates CC, Krishna P, Whaley D, Bodnar RJ, Turner T, Wells A,; Lack of CXC Chemokine Receptor 3 (CXCR3) Signaling Leads to Hypertrophic and Hypercellular Scarring. (2010) American Journal of Pathology Vol. 176, p. 1743-1755
Bodnar RJ, Yates CC, Rodgers MG, Du X, Wells A,; IP-10 induces dissociation of newly-formed vessels., (2009) Journal of Cell Science, Vol. 122 p.2064-2077