Dr. Chris Kevil’s laboratory at LSU Health Shreveport (LSUHS) has discovered that a clinically approved cyclodextrin-based drug called Sugammadex can act as a hydrogen sulfide donor that restores vasoactive hydrogen. This innovation has already gone through initial in vivo testing with promising results. Read Article (October 26, 2022)

JanOne Inc. has licensed a discovery by Dr. Chris Kevil that may treat peripheral artery disease: PRNewswire, Street Insider, Yahoo Finance. (June 7, 2022)

Dr. Chris Kevil has been awarded a five-year $10.5 million Centers of Biomedical Research Excellence (COBRE) grant by the National Institutes of Health.  He is the principal investigator of the project that will advance understanding of redox regulation of cardiovascular disease.

Dr. Chris Kevil and John Glawe were awarded US Patent # 10,254,262 for a Hydrogen Sulfide Detecting Apparatus on April 9, 2019.  This device can be used to measure concentrations of hydrogen sulfide in a given sample.

Dr. Chris Kevil presented his talk entitled “Sulfane Sulfur in Cardiovascular Disease” at the thirteenth biennial Nitric Oxide Gordon Research Conference held in Ventura, CA from February 3-8, 2019.

Work from our laboratory has published new insights into how the gasotransmitter hydrogen sulfide (H2S) regulates ischemic vascular remodeling and how its metabolites are affected during clinical cardiovascular disease. While the field of H2S biomedical research has grown, many key gaps remain in understanding how sulfide metabolites are formed in the vasculature and their ultimate fate. In brief, our team revealed that H2S bioavailability quickly increases during chronic vascular/tissue ischemia contributing to a compensatory increase in nitric oxide levels. We further found that hydrogen sulfide dependent nitric oxide (NO) enhancement occurs in a dual fashion through its generation by nitric oxide synthases and by stimulation of nitrite reduction back to NO in a xanthine oxidase dependent manner.

Redox Regulation of Therapeutic Vascular Remodeling - Therapeutic revascularization of ischemic tissue represents a major goal of numerous disorders including peripheral artery disease, stroke, myocardial infarction, diabetes and wound healing. A major focus of our laboratory involves addressing novel concepts and mechanisms of redox regulation of ischemic vascular remodeling and growth responses that are regulated by the NO endocrine system involving nitrite anion metabolism. Our lab is currently working on mechanisms of hydrogen sulfide (H2S) regulation of ischemic angiogenesis and arteriogenesis through its interactions with NO and its metabolites. We use advanced analytical metabolic profiling methods coupled with tissue-specific gene mutant animal models to identify specific H2S chemical reactants. Through this work, intellectual property has moved towards the clinic to identify novel therapeutics to selectively stimulate ischemic tissue vascular growth and perfusion.

Role of CSE in Regulation of Autophagy - Autophagy is a conserved catabolic process, which literally means the cell “eats itself”. Autophagy gets activated when there is nutrient depletion or other stress conditions. During autophagy, the cytoplasmic constituents and organelles of a cell are sequestered within double membrane vacuoles, called ‘autophagosomes’, and subsequently delivered to the lysosome for degradation, thus maintaining nutrient homeostasis. During peripheral artery disease, autophagy primarily functions as a cell survival response during nutrient deprivation and oxidative stress conditions. Our laboratory focuses on how CSE regulates autophagy in ischemic endothelial cells using both in vitro and in vivo models. Currently our three main goals in this project are: 1) to determine if CSE regulates autophagy in endothelial cells during ischemic stress conditions; 2) to delineate how CSE controls autophagy during PAD in vivo and ischemic endothelial cells in vitro; 3) dissect the mechanism by which CSE controls autophagy (Atg proteins) to ultimately exploit this process for therapeutic benefit for vascular adaptive response.

Leukocyte Recruitment in Type 1 Diabetes - Type 1 Diabetes (T1D) is an autoimmune disease affecting several million people worldwide with an incidence rate that is increasing at an alarming rate.  One of the hallmark features of T1D is infiltration of autoreactive T cells into the pancreatic islets.

Our lab has considerable experience investigating the mechanisms of T cell infiltration and has discovered that the chemokine SDF-1 causes reduced adhesion of T cells taken from Non-obese Diabetic mice, but increased adhesion of T cells from nondiabetic mice.  We have determined that this differential regulation is a result of Robo1-Slit2 interactions, whereby Slit2 converts an attractive signal via SDF into a repellant signal.  We are currently investigating the potential of Slit2 as a therapeutic agent and of Robo1 levels as an additional risk marker for development of T1D.

Selected Publications

1. Rajpal S, Katikaneni P, Deshotels M, Pardue S, Glawe J, Shen X, Akkus N, Modi K, Bhandari R, Dominic P, Reddy P, Kolluru GK, Kevil CG. Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease. Redox Biol. 2018 May;15:480-489. doi: 10.1016/j.redox.2018.01.007. Epub 2018 Feb 3. PubMed PMID: 29413960.
2. Whitener RL, Gallo Knight L, Li J, Knapp S, Zhang S, Annamalai M, Pliner VM, Fu D, Radichev I, Amatya C, Savinov A, Yurdagul A Jr, Yuan S, Glawe J, Kevil CG, Chen J, Stimpson SE, Mathews CE. The Type 1 Diabetes-Resistance Locus Idd22 Controls Trafficking of Autoreactive CTLs into the Pancreatic Islets of NOD Mice. J Immunol. 2017 Dec 15;199(12):3991-4000. doi: 10.4049/jimmunol.1602037. Epub 2017 Nov 6. PubMed PMID: 29109122; PubMed Central PMCID: PMC5716886.
3. Leskova A, Pardue S, Glawe JD, Kevil CG, Shen X. Role of thiosulfate in hydrogen sulfide-dependent redox signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2017 Aug 1;313(2):H256-H264. doi: 10.1152/ajpheart.00723.2016. Epub 2017 May 26. PubMed PMID: 28550177; PubMed Central PMCID: PMC5582921.
4. Yuan S, Shen X, Kevil CG. Beyond a Gasotransmitter: Hydrogen Sulfide and Polysulfide in Cardiovascular Health and Immune Response. Antioxid Redox Signal. 2017 Oct 1;27(10):634-653. doi: 10.1089/ars.2017.7096. Epub 2017 Jun 1. Review. PubMed PMID: 28398086; PubMed Central PMCID: PMC5576200.
5. Kolluru GK, Shen X, Yuan S, Kevil CG. Gasotransmitter Heterocellular Signaling. Antioxid Redox Signal. 2017 Jun 1;26(16):936-960. doi: 10.1089/ars.2016.6909. Epub 2017 Apr 6. PubMed PMID: 28068782; PubMed Central PMCID: PMC5455259.
6. Yuan S, Pardue S, Shen X, Alexander JS, Orr AW, Kevil CG. Hydrogen sulfide metabolism regulates endothelial solute barrier function. Redox Biol. 2016 Oct;9:157-166. doi: 10.1016/j.redox.2016.08.004. Epub 2016 Aug 11. PubMed PMID: 27552214; PubMed Central PMCID: PMC4993857.
7. Yuan S, Kevil CG. Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Remodeling. Microcirculation. 2016 Feb;23(2):134-45. doi: 10.1111/micc.12248. Review. PubMed PMID: 26381654.
8. Kolluru GK, Bir SC, Yuan S, Shen X, Pardue S, Wang R, Kevil CG. Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment. Cardiovasc Res. 2015 Sep 1;107(4):590-600. doi: 10.1093/cvr/cvv198. Epub 2015 Jul 20. PubMed PMID: 26194202; PubMed Central PMCID: PMC4540149.
9. Kolluru GK, Yuan S, Shen X, Kevil CG. H2S regulation of nitric oxide metabolism. Methods Enzymol. 2015;554:271-97. doi: 10.1016/bs.mie.2014.11.040. Epub 2015 Jan 17. PubMed PMID: 25725527; PubMed Central PMCID: PMC4413936.
10. Shen X, Kolluru GK, Yuan S, Kevil CG. Measurement of H2S in vivo and in vitro by the monobromobimane method. Methods Enzymol. 2015;554:31-45. doi:10.1016/bs.mie.2014.11.039. Epub 2015 Jan 10. PubMed PMID: 25725514; PubMed Central PMCID: PMC4413952.
11. Peter EA, Shen X, Shah SH, Pardue S, Glawe JD, Zhang WW, Reddy P, Akkus NI, Varma J, Kevil CG. Plasma free H2S levels are elevated in patients with cardiovascular disease. J Am Heart Assoc. 2013 Oct 23;2(5):e000387. doi: 10.1161/JAHA.113.000387. PubMed PMID: 24152982; PubMed Central PMCID: PMC3835249.
12. Bir SC, Pattillo CB, Pardue S, Kolluru GK, Shen X, Giordano T, Kevil CG. Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner. Diabetes. 2014 Jan;63(1):270-81. doi: 10.2337/db13-0890. Epub 2013 Sep 5. PubMed PMID: 24009258; PubMed Central PMCID: PMC4179307.
13. Kolluru GK, Shen X, Bir SC, Kevil CG. Hydrogen sulfide chemical biology: pathophysiological roles and detection. Nitric Oxide. 2013 Nov 30;35:5-20. doi: 10.1016/j.niox.2013.07.002. Epub 2013 Jul 9. Review. PubMed PMID: 23850632; PubMed Central PMCID: PMC4077051.
14. Glawe JD, Mijalis EM, Davis WC, Barlow SC, Gungor N, McVie R, Kevil CG. SDF-1-CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1-SLIT2 interactions in mice. Diabetologia. 2013 Oct;56(10):2222-30. doi: 10.1007/s00125-013-2978-x. Epub 2013 Jun 28. PubMed PMID: 23811810.

Complete List of my Published Work in My Bibliography:
https://www.ncbi.nlm.nih.gov/pubmed/?term=Kevil+CG%5BAuthor%5D

Postdoctoral Fellows

We are not actively recruiting Postdoctoral Fellows but exceptional applicants will always be considered.
 

Graduate Students

Graduate students interested in research in the Kevil Lab should review the list of available projects and contact Dr. Kevil at ckevil@lsuhsc.edu.

Contact Us

LSU Health Shreveport
Department of Pathology
BRI Room F7-21
1501 Kings Hwy
Shreveport, LA 71103

Chris Kevil, PhD
Phone:
(318) 675-4101 (office)
(318) 675-4208 (lab)
Fax: (318) 675-8144
Email: chris.kevil@lsuhs.edu