Arif Yurdagul, Jr., PhD
Assistant Professor of Molecular and Cellular Physiology
BS - Louisiana Tech University
PhD - LSU Health Shreveport
Post-doctoral Training (Molecular Medicine) - Columbia University
Research
Despite advances in surgical intervention and cholesterol-lowering drugs over the last few decades, atherosclerotic cardiovascular disease remains the leading cause of death worldwide. Atherosclerosis forms when modified low-density lipoproteins (LDL) accumulate in the subendothelial matrix of medium-sized arteries in areas of branch points, curvatures, and bifurcations, which generate a sustained inflammatory response in endothelial cells and drive leukocyte recruitment. Many of these infiltrating leukocytes become apoptotic, and while these dead cells are efficiently cleared by macrophages (termed “efferocytosis”) early in lesion formation, efferocytosis begins to fail as atherosclerosis progresses, resulting in an overabundance of post-apoptotic dead cells in an area of the atheroma called the necrotic core. In humans, plaques with large necrotic cores and thin fibrous caps are vulnerable to rupture, leading to myocardial infarction and stroke. Therefore, revealing the mechanisms by which efferocytosis fails as atherosclerosis progresses and how efferocytosis is restored during atherosclerosis regression are important objectives in the Yurdagul lab. With these goals in mind, we hope to identify new therapeutic approaches to curb atherosclerotic cardiovascular disease.
Nutrient Sensing of Apoptotic Cell-Derived Cargo by Macrophages
After an internalized apoptotic cell has been broken down to its basic cellular components within the phagolysosome, macrophages must either efflux these apoptotic cell-derived molecules to rid themselves from an overabundance of noxious materials or metabolize them into downstream products that are less toxic. Interestingly, some of these metabolites are instead beneficial to the macrophage and instruct a coordinated response to drive phagocytosis of more dead cells, termed “continual efferocytosis”. However, many questions remain surrounding the links between the metabolism of degraded apoptotic cells and continual efferocytosis, such as: (1) how does a macrophage sense the nutrients contained within the phagolysosome, (2) what metabolic pathways must be cued to properly handle apoptotic cell-derived cargo safely, and (3) how does nutrient-sensing of apoptotic cells and continual efferocytosis drive the resolution of inflammation and atherosclerosis regression. Our current research seeks to elucidate the cellular and molecular mechanisms underlying these functions and leverage these pathways to enhance inflammation resolution when it fails.
ODC-Dependent Putrescine Synthesis Regulates Smooth Muscle Cell Phenotype
Phenotypic modulation of vascular smooth muscle cells (SMCs), including changes in proliferation and migration, directly contribute to the progression of atherosclerosis, hypertension, and restenosis. Upon activation, vascular SMCs shift from a quiescent phenotype, characterized by a low rate of proliferation and exclusive expression of SMC-specific genes, towards a synthetic state, characterized by high rates of proliferation, a loss in expression of SMC-specific genes, and a heightened state of inflammation. Although this fibroproliferative remodeling expands plaque size, SMC-rich fibrous caps overlying large necrotic cores provide mechanical stability and lower the risk of rupture and sudden cardiac death. While the mechanisms that regulate smooth muscle cell phenotype during atherosclerosis progression are being defined, the role of SMC phenotypic modulation during regression remains largely unexplored. Our data indicate an essential role for polyamine metabolism in regulating fibrous cap formation, as we have shown that putrescine levels rise substantially during atherosclerosis regression and ODC-dependent putrescine synthesis governs SMC phenotype. Our current research aims to define the cellular and molecular mechanisms by which ODC-dependent putrescine synthesis regulates the stability of atherosclerotic plaques and identify theranostic platforms to deliver putrescine specifically to lesions in a manner that stabilizes rupture-prone plaques.
Publications
Selected Publications
- Stroope C, Nettersheim FS, Coon B, Finney AC, Schwartz MA, Ley K, Rom O, Yurdagul A Jr*. Dysregulated Cellular Metabolism in Atherosclerosis: Mediators and Therapeutic Opportunities (2024). Nature Metabolism. PMID: 38532071.
- Seeley EH, Liu Z, Yuan S, Stroope C, Cockerham E, Rashdan NA, Delgadillo LF, Finney AC, Kumar D, Das S, Razani B, Liu W, Traylor J, Orr AW, Rom O*, Pattillo CB*, Yurdagul A Jr*. Spatially Resolved Metabolites in Stable and Unstable Human Atherosclerotic Plaques Identified by Mass Spectrometry Imaging (2023). Arterioscler. Thromb. Vasc. Biol. PMID: 37381983. *Selected for Commentary by ATVB.
- Kumar D, Pandit R, Yurdagul A Jr. Mechanisms of Continual Efferocytosis by Macrophages and its Role in Mitigating Atherosclerosis (2023). Immunometabolism. PMID: 36710920.
- Yurdagul A Jr. Crosstalk Between Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Plaque Stability (2022). Arterioscler. Thromb. Vasc. Biol. PMID: 35172605.
- Yurdagul A Jr*, Kong N, Gerlach BD, Wang X, Ampomah P, Kuriakose G, Tao W, Shi J, Tabas I (2021). ODC-Dependent Putrescine Synthesis Maintains MerTK Expression to Drive Resolution. Arterioscler. Thromb. Vasc. Biol. PMID: 33406854. *Co-Corresponding Author. **Selected as the cover of the journal issue.
- Tao Wei*, Yurdagul A Jr*, Kong N, Li W, Wang X, Doran AC, Feng C, Wang J, Islam MA, Farokhzad OC, Tabas I, Shi J. siRNA Nanoparticles Targeting CaMKIIγ in Lesional Macrophages Improve Atherosclerotic Plaque Stability in Mice (2020). Science Translational Medicine. PMID: 32718990. *Co-first Author. ** Selected as the cover of the journal issue. Commentary: Research Highlight-Nanoparticles to Target Lesional Macrophages in Atherosclerotic Mice. Nature Reviews Cardiology (2020). Preview-Macrophage Targeted Gene Therapy to Improve Atherosclerotic Plaque Stability. Matter.
- Yurdagul A Jr*, Subramanian M, Wang X, Crown SB, Ilkayeva O, Darville L, Kolluru G, Rymond CC, Gerlach BD, Zheng Z, Kuriakose G, Kevil CG, Koomen JM, Cleveland JL, Muoio DM, Tabas I. Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury (2020). Cell Metabolism. PMID: 32004476. *Co-Corresponding Author. *Selected by Faculty Opinions. Commentaries: Editors’ Choice. Boosting Arginine Metabolism to Regress Atherosclerosis? Science Translational Medicine. Preview. Appetite for Arginine: Metabolic Control of Macrophage Hunger. Cell Metabolism.
- Doran AC, Yurdagul A Jr, Tabas I. Efferocytosis in Health and Disease (2019). Nature Reviews Immunology. PMID: 31822793.
- Back M, Yurdagul A Jr, Tabas I, Oorni K, Kovanen PT. Inflammation and its Resolution in Atherosclerosis: Mediators and Therapeutic Opportunities (2019). Nature Reviews Cardiology. PMID: 30846875. *Selected by Faculty of 1000.
- Wang Y.*, Subramanian M.*, Yurdagul A Jr*, Barbosa-Lorenzi VC, Cai B, de Juan-Sanz J, Ryan TA, Nomura M, Maxfield FR., Tabas IA. Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages (2017). Cell. *Co-first author. *Selected by Faculty of 1000
Complete List of my Published Work in MyBibliography: LEARN MORE
Team
Dhananjay Kumar, PhD
Postdoctoral Fellow
I aim to understand the mechanisms leading to putrescine accumulation in metabolic associated steatohepatitis (MASH), how putrescine drives hepatic fibrosis during MASH, and leverage our findings to create new therapeutic approaches for treating this disease.
Alex Hudson
Graduate Student
Macrophages ingest large amounts of nutrients when clearing dead cells. My work focuses on how macrophages sense and metabolize apoptotic cell-derived nutrients and elucidating the mechanisms by which these processes control inflammation resolution and atherosclerosis.
Rajan Pandit
Graduate Student
I study the role of extracellular matrix remodeling in macrophage function during inflammation and its resolution.
Louise Frausto
Graduate Student
My work focuses on understanding the links between impaired putrescine biosynthesis in vSMCs to ECM degradation and vascular calcification during plaque instability.
Theresea-Anne Governale
Lab Associate
I maintain lab equipment and supplies, collect and analyze data, ensure compliance with safety protocols and procedures, and maintain various transgenic and conditional knockout mouse lines.
Peyton Wilhite
Medical Student - Research Distinction
I'm interested in the mechanisms controlling fibronectin-mediated TIM3 expression in macrophages during atherosclerosis regression.
News
December 2024 - Congratulations to Dhananjay Kumar for obtaining an American Heart Association Postdoctoral Fellowship Award!
December 2024 - Dr. Yurdagul has been invited to co-organize the 2026 Vascular Biology meeting hosted by NAVBO and organize the 2027 meeting.
October 2024 - Dr. Yurdagul was announced as the Co-Director for the Metabolic and Liver Disease Research Program (https://research.lsuhs.edu/programs/metabolic-and-liver-disease-research-program)
September 2024 - Dr. Yurdagul was recognized in Stanford/Elsevier's List of the World's Top 2% of Scientists.
March 2024 - Our Review "Dysregulated Cellular Metabolism in Atherosclerosis: Mediators and Therapeutic Opportunities" was published in Nature Metabolism.
November 2023 - Congratulations to Rajan Pandit for obtaining the CCDS Malcolm Feist Predoctoral Fellowship Award!
September 2023 - Drs. Rom and Yurdagul received the Chancellor's Pathways Research Award to pursue the role of dysregulated putrescine metabolism in metabolic dysfunction-associated steatohepatitis (MASH).
June 2023 - Congratulations to Dr. Dhananjay Kumar for obtaining the CCDS Malcolm Feist Postdoctoral Fellowship Award!
June 2023 - Our manuscript "Spatially Resolved Metabolites in Stable and Unstable Human Atherosclerotic Plaques Identified by Mass Spectrometry Imaging" was published in ATVB and was selected for a Commentary.
March 2023 - The Yurdagul Laboratory was awarded an NIH R01 Award to study dysregulations in polyamine metabolism during atherosclerosis.
February 2023 - Dr. Yurdagul was selected as a finalist for the 2023 Irvine H. Page Junior Faculty Research Award by the ATVB Council of the American Heart Association.
June 2022 - The Yurdagul Laboratory and Ari Cohen at Ochsner Health System, in collaboration with the Rom laboratory at LSU Health Shreveport, have received the Collaborative Intramural Research Program (CIRP) Award to investigate the role of dysregulated polyamine homeostasis in NASH progression.
April 2022 - Dr. Yurdagul received the Institution's Research Rising Star Award at the Annual Research Celebration.
Photos
Vascular Discovery 2024
Vascular Discovery 2024 from May 15–18, 2024 in Chicago, Illinois
Yurdagul lab, Rom lab, Orr lab, and friends dining at Flat Top Grill in Chicago.
Bishuang won the Page Award - congratulations Bishuang, well deserved!
(Bishuang, Ze, Lale, Art, and Oren; left to right)
Art, Ed, Amanda, Mani, Ze, Gabby and Lale taking a group photo!
Bishuang won the Page Award - congratulations Bishuang, well deserved!
(Ze, Art, Bishuang, Gabby, Lale, and Amanda; left to right)
LSU Health Shreveport representing at Vascular Discovery 2024!
(Naznin, Wayne, Peyton, Art, Nirav, Oren, Rajan, and Dhananjay; left to right)
Yurdagul Lab Kingpin Cup 2024
Positions
Post-doctoral Fellows
Graduating PhD candidates interested in conducting research in the Yurdagul lab should review the current laboratory research directions and contact Dr. Yurdagul at arif.yurdagul@lsuhs.edu.
Graduate Students
Graduate students interested in conducting research in the Yurdagul lab should review the current laboratory research directions and contact Dr. Yurdagul at arif.yurdagul@lsuhs.edu.
Undergraduate Research Assistants
The Yurdagul laboratory has a number of research projects available for undergraduate students who are interested in gaining research experience and learning new techniques. Most positions are available in the summer. Those who are interested should contact Dr. Yurdagul directly at arif.yurdagul@lsuhs.edu.
Medical Students, Residents, and Fellows
The Yurdagul laboratory has a number of research projects available for any Medical Students, Residents, and Fellows. Those who are interested should contact Dr. Yurdagul directly at arif.yurdagul@lsuhs.edu.
Contact Us
Contact Us
LSU Health Shreveport
Department of Molecular & Cellular Physiology
1501 Kings Hwy, BRI F4-22
Shreveport, LA 71103
Email:
arif.yurdagul@lsuhs.edu
Office:
(318) 675-4229
Lab:
(318) 675-4231
(318) 675-4210