David Jourd'heuil, PhD
Areas of Study
Redox Signaling, Vascular Smooth Muscle, Cardiovascular Disease and Inflammation, Nitric Oxide, Free Radical Chemical Biology
- University of Calgary, Canada1996PhysiologyPhD
- University of Bordeaux, France1991PharmacologyDEA
- University of Bordeaux, France1989BiochemistryBS
My laboratory pursues the theme of vascular injury, adaptation, and remodeling in the context of mechanisms that contribute to several disorders such as atherosclerosis, post-angioplasty restenosis, vein graft stenosis, and arteriovenous fistula non-maturation or failure. We use approaches based on transgenic animal models, ex vivo culture of diseased human vessels, primary cell cultures derived from vessels, and in vitro biochemical systems. Some of these studies are part of collaborative efforts between the Department of Molecular and Cellular Physiology and the nephrology team at the Albany Med Health System.
Our laboratory collaborates with other initiatives at Albany Medical College and in the greater Capital Region that explore redox biology and nitric oxide (NO) physiology and pathophysiology in the context of stroke, cancer, asthma, and pulmonary diseases. We provide expertise in Redox Biology and NO metabolomics to assist our collaborators and other investigators.
Specific attention is given to the following areas:
Integration of Redox Signaling to Vascular Smooth Muscle Cell Biology
Vascular smooth muscle cells are the main cells that make up the walls of blood vessels, which are essential for distributing blood throughout the body. Smooth muscle cells are also important in some of the most prevalent diseases affecting the Western world. This includes hypertension (high blood pressure) and atherosclerosis (hardening of the arteries) leading to heart attack, peripheral artery disease, and stroke. In response to increased blood pressure, traumatic injury, and diseases, vascular smooth muscle cells can be induced to grow and migrate from their normal locations to contribute to the thickening of blood vessels that lead to plaque formation and cause clots and blood vessel blockage.
Many studies have shown that cardiovascular diseases in general are associated with an increase production of harmful oxidants, a condition generically called “oxidative stress”. However, most redox signaling networks that might regulate vascular homeostasis and disease have yet to be elucidated in sufficient detail to provide actionable therapeutic strategies. Our goal is to discover new redox-based mechanisms that contribute to the regulation of smooth muscle function in diseased vessels.
Biochemical and functional characterization of hemoglobins in the vascular wall
In addition to the oxygen transport hemoglobins such as red blood cell hemoglobin and heart myoglobin, mammals express several other globins with poorly characterized functions. We have focused our attention on cytoglobin (CYGB), which we have characterized in vessels and vascular smooth muscle cells as part of an adaptative pathway that may confer protection against injury in the vasculature. Mechanisms through which the cytoprotective effect of CYGB may arise (for example vasodilatory, anti-apoptotic, and anti-inflammatory actions) are explored and the involvement of nitric oxide and oxidant scavenging capacity in contributing to such cytoprotection is examined.
Chemistry of NO in the cardiovascular system
The major determinant of NO functions in biological systems is its chemistry. An important aspect of our research is improving our understanding of the chemical, biochemical, and cellular mechanisms dictating NO chemical reactivity. It is our aim to translate this knowledge to improve and modulate NO functions in the vasculature.
View David Jourd'heuil's articles on the National Institute of Health's PubMed website.
Clinton Mathai, Frances Jourd’heuil, Le Gia Cat Pham, Kurrim Gilliard, Dennis Howard, Joseph Balnis, Ariel Jaitovich, Sridar V. Chittur, Mark Rilley, Ruben Peredo-Wende, Ibrahim Ammoura, Sandra J. Shin, Margarida Barroso, Jonathan Barra, Evgenia Shishkova, Joshua J. Coon, Reynold I. Lopez-Soler, and David Jourd'heuil. Regulation of DNA damage and transcriptional output in the vasculature through a cytoglobin-HMGB2 axis. Redox Biol. 2023 Sep; 65:102838. doi: 10.1016/j.redox.2023.102838. Epub 2023 Aug 9.
Clinton Mathai, Frances Jourd'heuil, Le Gia Cat Pham, Kurrim Gilliard, Joseph Balnis, Annie Jen, Katherine A Overmyer, Joshua J Coon, Ariel Jaitovich, Benoit Boivin, and David Jourd'heuil. A role for cytoglobin in regulating intracellular hydrogen peroxide and redox signals in the vasculature. bioRxiv
Jonathan Barra, Isaiah Crosbourne, Ling Wang, Ramon Bossardi-Ramos, Frances Jourd'heuil, Iram Nelson, Alejandro Adam, David T. Corr, David Jourd'heuil, and Margarida Barroso. DMT1 bridges endosomes and mitochondria to modulate mitochondrial iron translocation. bioRxiv doi: 10.1101/2022.04.14.488402.
Sudeshna Sadhu, Christa Decker, Brian E. Sansbury, Michael Marinello, Allison Seyfried, Masayuki Mori, Zeinab Hosseini, Thilaka Arunachalam, Aloke V. Finn, John M. Lamar, David Jourd’heuil, Liang Guo, Katherine C. MacNamara, Matthew Spite, Gabrielle Fredman. Radiation-induced senescence impairs resolution programs and drives cardiovascular inflammation. J. Immunol. Oct 1;207(7):1812-1823. doi: 10.4049/jimmunol.2100284. Epub 2021 Aug 30. PMID: 34462312.
Joseph Balnis, Lisa A. Drake, Catherine E. Vincent, Tanner C. Korponay, Diane V. Singer, David Lacomis, Chun Geun Lee, Jack A. Elias, David Jourd'heuil, Harold A. Singer, and Ariel Jaitovich. Succinate Dehydrogenase (SDH)-subunit C regulates muscle oxygen consumption and fatigability in an animal model of pulmonary emphysema. Am J Respir Cell. Mol. Biol. 2021 Apr 28. doi: 10.1165/rcmb.2020-0551OC. PMID: 33909984.
Yongfeng Liu, Li-Yan Sun, Diane V. Singer, Roman Ginnan, Amy Spinelli, Wen Zhao, Frances Jourd’heuil, David Jourd’heuil, and Harold A. Singer. Thymine DNA Glycosylase (TDG) is a Key Regulator of CaMKIIγ Expression and Vascular Smooth Muscle Phenotype. Am. J. Physiol (Heart). 2019 Nov 1:317(5):H969-H980. PMID: 31518169.
Wen Wu, Jinjing Zhao, Wei Zhang, Mihyun Choi, Min Xue, David Jourd'heuil, Harold A. Singer, Xiaochun Long. Vascular Smooth Muscle MAPK14 Is Required for Injury-Induced Neointima Formation by Suppressing VSMC Differentiation and Inducing Proliferation and Inflammation. Redox Biol. Apr; 22:101137. Doi: 10.1016/j.redox.2019.101137. PMID: 30771750.
Zhen Wang, Alex Divanyan, Frances L. Jourd’heuil, R.D. Goldman, Karen M. Ridge, David Jourd’heuil, and Reynold Lopez-Soler. Vimentin expression affects the development of EMT-related renal fibrosis following unilateral ureteral obstruction in mice. Am. J. Physiol. 2018 Oct 1;315(4): F769-F780. doi: 10.1152/ajprenal.00340.2017. PMID: 29631355.
Frances L. Jourd’heuil, Haiyan Xu, Timothy Reilly, Keneta McKellar, Chaymae El Alaoui, Julia Steppich, Yong Feng Liu, Roman Ginnan, David Conti, Reynold Lopez-Soler, Arif Asif, Xiaochun Long, Harold A. Singer, and David Jourd’heuil. The Expression of the Hemoglobin Homolog Cytoglobin in Smooth Muscle Inhibits Apoptosis and Regulates Vascular Remodeling. Arterioscler. Thromb. Vasc. Biol. 2017 Oct;37(10):1944-1955. doi: 10.1161/ATVBAHA.117.309410. PMID: 28798140.
Shuning Zhang, Xiuchun Li, Frances L Jourd’heuil, Shunlin Qu, Neil Devijian, Edward Bennett, David Jourd’heuil*, and Chuanxi Cai*. Cytoglobin promotes cardiac stem cell survival against oxidative stress via the upregulation of the NFkB/iNOS signal pathway and nitric oxide production. Scientific Reports, 2017 Sep 7;7(1):10754. doi: 10.1038/s41598-017-11342-6. PMID: 28883470 *corresponding authors.
Jinjing Zhao, Frances L Jourd'heuil, Min Xue, David Conti, Reynold I. Lopez-Soler, Roman Ginnan, Arif Asif, Harold A. Singer, David Jourd'heuil*, and Xiaochun Long*. A Dual Function for Mature Vascular Smooth Muscle Cells during Arteriovenous Fistula Remodeling. JAHA, 2017 Mar 30;6(4). pii: e004891. doi: 10.1161/JAHA.116.004891.*corresponding authors.
Jinjing Zhao, Wen Wu, Wei Zhang, Emiley Tou, Jiemei Ye, Ping Gao, David Jourd'heuil, Harold A. Singer, Mingfu Wu and Xiaochun Long. TSPAN2 is a novel cell membrane gene closely associated with vascular smooth muscle contractile phenotype and is regulated by the TGFβ1/SMAD and MYOCD/SRF pathways. FASEB J., 2017 Mar 3. pii: fj.201601021R. doi: 10.1096/fj.201601021R.
Halligan KE, Jourd’heuil FL, and Jourd’heuil D. Cytoglobin is expressed in the vasculature and regulates cell respiration and proliferation via nitric oxide dioxygenation. J. Biol. Chem. 284(13):8539-8547, 2009.
Jourd’heuil D**, Jourd’heuil FL, Kutchukian P, Musah RA, Wink DA, and Grisham MB. Reaction of superoxide and nitric oxide with peroxynitrite. Implications for peroxynitrite-mediated oxidation reactions in vivo. J Biol Chem 276:28799-28805, 2001. ** Corresponding author.