Christopher Kevil, Ph.D.
Ph.D., 1998, Louisiana State University Health Sciences Center
Department of Pathology
LSU Health Sciences Center
1501 Kings Hwy
Shreveport, LA 71130
Major Research Interests: Redox Regulation of Therapeutic Vascular Remodeling. Therapeutic revascularization of ischemic tissues represents a major goal of numerous disorders such as peripheral artery disease, stroke, myocardial infarction, and wound healing. A major focus of our laboratory addresses novel concepts and mechanisms of redox regulation of ischemic vascular remodeling and growth responses that are regulated by the Nitric Oxide endocrine system involving nitrite anion metabolism. The lab is currently working on novel mechanisms of Hydrogen Sulfide regulation of ischemic angiogenesis and arteriogenesis through its interactions with nitric oxide metabolites using advanced analytical metabolic profiling methods identifying specific Hydrogen Sulfide chemical reactants coupled with tissue specific gene mutant animal models. Through this work, novel intellectual property has moved toward the clinic to identify novel therapeutics to selectively stimulate ischemic tissue vascular growth and perfusion.
Chronic Inflammation and Pathological Angiogenesis: Chronic inflammatory diseases (such as inflammatory bowel disease, atherosclerosis, and arthritis) have been shown to involve aberrant vascular growth and function. Work in our laboratory has revealed that endothelial cell regulatory molecules VEGF and caveolin-1 play key pathophysiological roles in mediated pathological angiogenesis during chronic inflammation of experimental colitis. Using whole genome profile analysis, our laboratory has identified several new previously unknown redox molecular targets and pathways that participate during colitis pathological angiogenesis. Results from this work represent unique therapeutic approaches for inhibiting pathological angiogenesis and chronic inflammation, while providing greater understanding of pathological versus physiological vascular remodeling responses.
Regulation of Leukocyte Recruitment during Autoimmunity and Chronic Inflammation: Initiation and maintenance of autoimmune and chronic inflammatory pathologies rely on the ability of various leukocytes to home to target tissues and exit the intravascular space. Studies in our laboratory have identified important leukocyte integrin adhesion molecule functions that regulate immune cell attachment and emigration across vascular endothelium, which are obligatory events for leukocyte homing. We have further identified a novel chemokine (CXCL12) mediated chemorepulsion response preventing diabetogenic T cell adhesion to pancreatic islet microvascular endothelial cells representing a novel approach to controlling autoimmune cell recruitment during Type 1 diabetes. Future directions of this work are aimed at better understanding this chemokine mediated chemorepulsion response and to determine whether such events might be useful at attenuating experimental autoimmune diabetes in animal models.
Ongoing cardiovascular-related projects:
1. Hydrogen sulfide regulation of ischemic vascular remodeling
Brief description: This project focuses on the role of hydrogen sulfide metabolism responses in regulating ischemia mediated angiogenesis vascular growth and reperfusion of tissues.
Names of collaborators / collaborating institutions: Dr. Wayne Orr, collaborator
Funding source: NIH
2. Hydrogen sulfide regulation of endothelial solute permeability
Brief description: This project focuses on determining the role of hydrogen sulfide metabolism responses on endothelial solute barrier function using in vivo and in vitro approaches.
Names of collaborators / collaborating institutions
Funding source: CCDS
3. Novel lab on a chip sensor development for H2S detection
Brief description: This project focuses on developing a novel H2S lab on a chip detection device that rapidly measures bioavailable H2S.
Names of collaborators / collaborating institutions: Dr. Leland Weiss, Louisiana Tech University
Funding source: CCDS Partners Across Campuses grant
Planned cardiovascular-related projects:
- Gasotransmitter regulation of cardiovascular aging – This project investigates H2S and NO bioavailability in the cardiovascular system during aging and how this may be altered therapeutically.
- Redox network regulation of vascular growth and remodeling – This project will investigate how redox metabolites influence on another to regulate ischemic angiogenesis and arteriogenesis responses
- Shear stress regulation of cardiovascular gasotransmitter bioavailability – This project investigates how shear stress regulates H2S and NO bioavailability in the cardiovascular system.
Methods and Available Resources:
- Single point probe laser doppler
- SPY imager system
- Shimadzu HPLC system (UV and fluorescent detection)
- NO chemiluminescent analyzer
- Hypoxia chamber glove box
- Unilateral femoral artery ligation/hind limb ischemia model
- Matrigel plug angiogenesis assay
- Miles permeability assay
- ICG permeability assay
- DSS colitis
- Adoptive T cell transfer colitis
- scratch-wound healing assay
- single cell migration assay
- tube formation assay
- transwell permeability assay
- transwell co-culture proliferation assay
- leukocyte-endothelial cell adhesion assay (static and hydrodynamic flow)
- hypoxia-reoxygenation assays
- Monobromobimane measurement of H2S by HPLC and LC/MS
- DHE measurement of superoxide by HPLC
- NO measurement by HPLC and chemiluminescent analysis
- GSH measurement by HPLC
- Thiol measurement by HPLC and immunoblotting