Paul D Chantler, PhD

Research Interests

Research in my laboratory is focused on vascular biology and how certain disease states (obesity, and aging) or conditions (chronic stress, E-cig, or exercise) mediates vascular biology. My lab operates with both human and animal models; this dual approach allows us to further explore the mechanisms underlying the vascular consequences of disease progression. We have shown that the fat around the aorta plays a significant role on vascular health and disease progression. Recently, we have focused on the microvessels in the brain, and how vascular damage here contributes to cognitive impairment and VCID. Indeed, we have shown that chronic stress is involved in accelerating VCID due to a pro-oxidative microenvironment impacting the cerebrovascular network, resulting in impaired vascular function, structure, and a loss of vessels. This project is currently funded by NIH for the next 4 years (2021-2025).

Another area of focus is the role of E-cig exposure on vascular function. In collaboration with Dr. Olfert, we started off and examined the chronic (8-months) effects of e-cig exposure on aortic function and stiffness in adult mice. We report that E-cig exposure for the equivalent of ~25 yr of exposure in humans increased arterial stiffness and impaired aortic reactivity, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease. We have also shown that rats exposed to e-cig while pregnant causes severely impaired cerebrovascular dysfunction and aortic stiffness. This project is currently funded by NIH and AHA.

As a member of the Center for Inhalation Toxicology and the Center for Basic and Translational Stroke Research, and my strong collaborations outside of my lab (Phys Pharm, neuroscience, immunology, etc.) ensures that the lab is positioned in a fertile and collaborative environment conducive to ensure successful attainment of the research goals.

Specific areas of interest include:

• Chronic stress & vascular contributions to cognitive impairment & dementia (VCID)
• Electronic cigarettes and vascular dysfunction
• Obesity & exercise and their role in vascular biology

Grants and Research

Current Grants and Contracts

• NIH, NINDS BINP R01 NS117754, Psychosocial Stress-Induced Vascular Contributions to Cognitive Impairment and Alzheimer’s Disease: The Role of Xanthine Oxidase ($2,032,732)
  • PI Chantler
  • 9/1/21 - 7/31/25
  • Score: 3%
• NIH, NIEHS, R21ES033026-01, Effects of Electronic Cigarette Wattage Setting on Vascular Harm ($418,000)
  • Co-PIs Olfert and Chantler
  • 9/1/20 - 8/31/22
• AHA Collaborative Sciences Award #20CSA35320107, Vascular Dysfunction in Offspring Exposed to Maternal Vaping ($750,000)
  • Co-PIs Olfert, Chantler, Boyd, Dakhallah
  • 1/30/20 - 12/31/23

Completed Grants and Contracts

PI unless otherwise stated

• NIH, BINP R56 NS117754-01, Psychosocial Stress-Induced Vascular Contributions to Cognitive Impairment and Alzheimer’s Disease: The Role of Xanthine Oxidase, 9/15/20 - 8/31/21
• WV CTSI Pilot Grant Program ($50,000), 2017 - 2018
• NIH, West Virginia Stroke CoBRE (P20 GM109098), 2014 - 2017
  • PI Simpkins, Project PI Chantler ($1,000,000)
• ​WVU CTSI Pilot Grant Program ($50,000), 2014 - 2016
• CereDx “Stroke Biomaker” Project ($11,234.99), 2016 - 2017
• Claude Benedum Foundation “Building HOPE in West Virginia," 2014 - 2015
  • Project PI Chantler ($40,000)
• National Swimming Pool Foundation Grant ($50,000), 2012 - 2014
• AHA Clinical Program Research Grant ($121,000), 2011 - 2013
• WVU Program to Stimulate Competitive Research ($27,1000), 2012 - 2013
• NIH/NHLBI, West Virginia Community Genetics Project (CO-I-5%), 2012 - 2014
• WVU Research Foundation Development Grant ($22,100), 2011 - 2012

Publications

Recent Publications in Refereed Journals

1. Mills A, Frazier J, Plants R, Burrage E, Coblentz T, Nassabeh S, Robinson M, Chantler PD, Olfert IM. Effects of electronic cigarette E-liquid and device wattage on vascular function. Toxicol Appl Pharmacol. 2023 Sep 1;474:116631. PMID: 37468077
2. Aboaziza E, Feaster KM, Hare L, Chantler PD, Olfert IM. Maternal electronic cigarette use during pregnancy affects long-term arterial function in offspring. J Appl Physiol. 2022 Nov 23; Online ahead of print. PMID: 36417201
3. Kunovac A, Hathaway QA, Burrage EN, Coblentz T, Kelley EE, Sengupta PP, Hollander JM, Chantler PD. Left ventricular segmental strain identifies unique myocardial deformation patterns after intrinsic and extrinsic stressors in mice. Ultrasound Med Biol. 2022 Aug 3;S0301-5629(22)00437-9. Online ahead of print. PMID: 35933241
4. Halvorson BD, Menon NJ, Goldman D, Frisbee SJ, Goodwill AG, Butcher JT, Stapleton PA, Brooks SD, d'audiffret AC, Wiseman RW, Lombard JH, Brock RW, Olfert IM, Chantler PD, Frisbee JC. The development of peripheral microvasculopathy with chronic metabolic disease in obese Zucker rats: a retrograde emergence? Am J Physiol Heart Circ Physiol. 2022 Jul 29; Online ahead of print. PMID: 35904886
5. Mills A, Dakhlallah D, Robinson M, Kirk A, Llavina S, Boyd JW, Chantler PD, Olfert IM. Short-term effects of electronic cigarettes on cerebrovascular function: A time course study. Exp Physiol. 2022 Jun; Online ahead of print. PMID: 35661445
6. Lewis SE, Rosencrance CB, De Vallance E, Giromini A, Williams XM, Oh JY, Schmidt H, Straub AC, Chantler PD, Patel RP, Kelley EE. Human and rodent red blood cells do not demonstrate xanthine oxidase activity or XO-catalyzed nitrite reduction to NO. Free Radic Biol Med. 2021 Oct;174:84-88. PMID: 34273539
7. Burrage EN, Aboaziza E, Hare L, Reppert S, Moore J, Goldsmith WT, Kelley EE, Mills A, Dakhlallah D, Chantler PD, Olfert IM. Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy. Am J Physiol Heart Circ Physiol. 2021 Aug 1;321(2):H339-H352. PMID: 34170194
8. Boateng SY, Olfert IM, Chantler PD. Role of perivascular adipose tissue and exercise on arterial function with obesity. Exerc Sport Sci Rev. 2021 Jul 1;49(3):188-196. PMID: 33831902
9. DeVallance ER, Branyan KW, Olfert IM, Pistilli EE, Bryner RW, Kelley EE, Frisbee JC, Chantler PD. Chronic stress induced perivascular adipose tissue impairment of aortic function and the therapeutic effect of exercise. Exp Physiol. 2021 Jun;106(6):1343-1358. PMID: 33913209
10. AlGhatrif M, Morrell CH, Becker LC, Chantler PD, Najjar SS, Ferrucci L, Gerstenblith G, Lakatta EG. Longitudinal uncoupling of the heart and arteries with aging in a community-dwelling population. Geroscience. 2021 Apr;43(2):551-561. PMID: 33598853

Recent Conference Abstracts

1. Prahbu S, Oudomvilay C, Burrage E, Lewis S, Hanshew A, Childers R, Maxwell B, Wood A, Choueiri M, Sissoko M, Walsh C, Kelley E, Chantler P. Cerebrovascular function is protected in hepatic xanthine oxidase knockout mice under chronic stress. American Physiology Summit 2023. Long Beach, CA. 2023 Apr. DOI: https://doi.org/10.1152/physiol.2023.38.S1.5731121
2. Prahbu S, Burrage E, Luthman J, Oudomvilay C, Luna N, Childers R, Hanshew A, Englund P, Tierno V, Hoover J, Simpkins J, Kelley E, Chantler P. Xanthine oxidase mediates stress-induced Alzheimer's Disease progression in triple transgenic mice. American Physiology Summit 2023. Long Beach, CA. 2023 Apr. DOI: https://doi.org/10.1152/physiol.2023.38.S1.5730102
3. Mills A, Nassabeh S, Frazier J, Robinson M, Legg P, Shamma A, Hurley A, Chantler P, Dakhallah D, Boyd, J, Olfert IM. Maternal vaping during pregnancy e-cigs leads to obesity in offspring. American Physiology Summit 2023. Long Beach, CA. 2023 Apr. DOI: https://doi.org/10.1152/physiol.2023.38.S1.5729326
4. Frazier JI, Mills A, Nassabeh S, Plants R, Robinson M, Kincaid S, Kottapalli D, Prabhu S, Chantler PD, Olfert IM. Low vs. high wattage vaping during pregnancy influences vascular function in rat offspring. Annual Experimental Biology Conference. Philadelphia, PA. 2022 Apr. DOI: https://doi.org/10.1096/fasebj.2022.36.S1.R5928
5. Ings S, Dallas M, Chantler PD, Boateng S. Differential remodelling of visceral and pericardial adipose tissue in response to stress and exercise. Annual Experimental Biology Conference. Philadelphia, PA. 2022 Apr. DOI: https://doi.org/10.1096/fasebj.2022.36.S1.R4464
6. Burrage EN , Prabhu S, Frazier J, Simpkins J, Kelley EE, Chantler PD. Chronic stress accelerates the progression of cerebrovascular dysfunction with Alzheimer’s Disease. Annual Experimental Biology Conference. Philadelphia, PA. 2022 Apr. DOI: https://doi.org/10.1096/fasebj.2022.36.S1.R2297
7. Burrage EN, Prabhu S, Frazier J, Englund P, Mills J, Casto M, Bryner RW, Kelley EE, Chantler PD. Global toll-like receptor 4 knockout prevents cerebrovascular dysfunction associated with chronic stress. Annual Experimental Biology Conference. Philadelphia, PA. 2022 Apr. DOI: https://doi.org/10.1096/fasebj.2022.36.S1.R2298
8. Prabhu S, Burrage EN, Simpkins J, Kelley EE, Chantler PD. Chronic stress exacerbates Tau production in the 3xTg Alzheimer’s Disease mice. Annual Experimental Biology Conference. Philadelphia, PA. 2022 Apr. DOI: https://doi.org/10.1096/fasebj.2022.36.S1.R4482
9. Mills A, Plants R, Nassabeh S, Bruce A, Robinson M, Chantler PD, Olfert IM. Maternal vaping effects on cerebrovascular function in offspring. Annual AHA Scientific Sessions. Boston, MA. 2021 Nov.
10. Mills A, Robinson M, Kirk A, Chantler PD, Olfert IM. Single exposure to electronic cigarettes induces cerebrovascular impairments up to 72 hours. NIH Tobacco Regulatory Science Meeting. Virtual. 2021 Oct.