We are interested in a chronic inflammatory disease called atherosclerosis, which is the leading cause of death in the developed countries. Atherosclerosis is characterized by atherosclerotic plaques in the medium and large arteries and the major components of the plaques are lipid-laden innate immune cells called macrophages. Using a variety of genetically modified mice as in vivo animal models together with in vitro cell culture model and many biochemical techniques, we study the molecular mechanisms underlying the pro-atherogenic functions of the macrophages.
 
We are also using novel state-of-the-art technologies including single cell RNA sequencing, high resolution confocal microscopy, Seahorse extracellular flux metabolic assays, GC-MS, and so on to explore cell expression network that are linked to immune activation and metabolic status. With these novel tools, we are able to study not only the macrophage functions but also the cross talk between macrophage and other cell types.

1. 04/01/2023 - 03/31/2027  R01HL164460 (Co-PI)
   “NKA/CD36 signaling in adipocytes promotes oxidative stress and drives chronic inflammation in atherosclerosis”
2. 04/01/2022 - 03/31/2025  American Heart Association Long-COVID Grant (Co-PI)
   “Role of TLR9 and mitochondrial DNA in regulating microvascular and immune cell dysfunction post-COVID-19”
3. 01/01/2023 - 12/31/2023 Advancing a Healthier Wisconsin Endowment, MCW-Led Seed Grant (PI)
   “Macrophage mitochondrial ROS disrupt cholesterol metabolism during atherosclerosis”

Jackie Chang, BS
Research Technologist

Vaya Chen, BE
Lab Manager and Technician

Lance Vick, BS
PhD Student

MyNCBI (Click Here)

Social Platforms

• Twitter: AlanChen16
• LinkedIn: http://www.linkedin.com/in/yiliang-c-24232b36

Selected Publications

1. *Yiliang Chen, Jue Zhang, Weiguo Cui, and Roy L. Silverstein. “CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate” Journal of Experimental Medicine. Jun.6, 2022; 219(6):e20211314 *Corresponding author.
2. Vaya Chen, Jue Zhang, Jackie Chang, Mirza Ahmar Beg, Lance Vick, Dandan Wang, Ankan Gupta, Yaxin Wang, Ziyu Zhang, Wen Dai, Mindy Kim, Shan Song, Duane Pereira, Ze Zheng, Joseph I. Shapiro, Roy L. Silverstein, Subramaniam Malarkannan, Yiliang Chen*. “CD36 Restricts Lipid-associated Macrophages Accumulation in White Adipose Tissues During Atherogenesis”. Frontiers in Cardiovascular Medicine. 2024. Aug 2:11:1436865. *Corresponding author.
3. Mirza Ahmar Beg, Minqi Huang, Lance Vick, KN Shashanka Rao, Jue Zhang, *Yiliang Chen. “Targeting Mitochondrial Dynamics and Redox Regulation in Cardiovascular Diseases” Trends in Pharmacological Sciences. 2024 Apr;45(4):290-303. *Corresponding author.
4. Sneha S. Pillai, Duane G Pereira, Jue Zhang, Wenxin Huang, Mirza Ahmar Beg, Darcy A. Knaack, Bruno de Souza Goncalves, Daisy Sahoo, Roy L. Silverstein, Joseph I. Shapiro, Komal Sodhi, Yiliang Chen*. “Contribution of adipocyte Na/K-ATPase α 1/CD36 signaling induced exosome secretion in response to oxidized LDL” Frontiers in Cardiovascular Medicine, 2023. Vol 10. *Corresponding author.
5. Jue Zhang, Jackie Chang, Mirza Ahmar Beg, Wenxin Huang, Yiqiong Zhao, Wen Dai, Xiaopeng Wu, Weiguo Cui, Sneha S. Pillai, Hari Vishal Lakhani, Komal Sodhi, Joseph I. Shapiro, Daisy Sahoo, Ze Zheng, Roy L. Silverstein, Yiliang Chen*. “Na/K-ATPase Suppresses LPS-Induced Pro-Inflammatory Signaling Through Lyn” iScience, 2022, 25 (9). *Corresponding author.
6. Hou Y, Wang Q, Han B, Chen Y, Qiao X, Wang L. "CD36 promotes NLRP3 inflammasome activation via the mtROS pathway in renal tubular epithelial cells of diabetic kidneys". Cell Death Dis. 2021 May 21;12(6):523.
7. Jue Zhang, Xin Li, Hui Yu, Isabel Larre, Sandrine V. Pierre, Zijian Xie, *Yiliang Chen. "Isoform-specific regulation of Na/K-ATPase by cholesterol is dependent on Na/K-ATPase/caveolin-1/src complex". American Journal of Physiology. 2020. Dec 1;319(6):C1107-C1119. *Corresponding author.
8. *Yiliang Chen, Moua Yang, Wenxin Huang, Wenjing Chen, Yiqiong Zhao, Marie L. Schulte, Peter Volberding, Zachary Gerbec, Michael T. Zimmermann, Atefeh Zeighami, Wendy Demos, Jue Zhang, Darcy Knaack, Brian C. Smith, Weiguo Cui, Subramaniam Malarkannan, Komal Sodhi, Joseph I. Shapiro, Zijian Xie, Daisy Sahoo, Roy L. Silverstein. "Mitochondrial metabolic reprogramming by CD36 signaling drives macrophage inflammatory responses". Circulation Research. 125(12):1087-1102. 2019. *Corresponding author.
   
   Featured Commentary in Circulation Research “Mitochondrial Indigestion After Lipid Scavenging”. 125(12): 1103-1105
9. *Yiliang Chen, Jue Zhang, Weiguo Cui, and Roy L. Silverstein. “CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate” Journal of Experimental Medicine. Jun.6, 2022; 219(6):e20211314 *Corresponding author.

1. NKA regulates cholesterol metabolism.  Since its discovery more than half a century ago, NKA was considered solely as a plasma membrane ion transporter until Dr. Zijian Xie and his colleagues demonstrated the signal transduction role of NKA in 2000. After I joined Dr. Xie’s group, I focused my work on the function of NKA signaling within caveolae, a lipid-enriched plasma membrane microdomain. I made a surprising finding that NKA not only regulated caveolin-1 protein, a cholesterol transporter, but also cholesterol membrane distribution. Moreover, we found that cholesterol has a feedback mechanism to modulate NKA membrane expression. It was the first time that NKA was linked to cellular cholesterol metabolism. Based on my work, we made an NKA-derived peptide that has a potential to alter cellular cholesterol distribution and metabolism and were granted a patent.
   1. Ting Cai, Haojie Wang, Yiliang Chen, Lijun Liu, William T Gunning, Luis Eduardo M. Quintas, Zi-Jian Xie. “Regulation of Caveolin-1 Membrane Trafficking by the Na/K-ATPase” J. Cell. Biol. Vol 182, No. 6, 1153-69, 2008. PMC2542476
   2. Yiliang Chen, Ting Cai, Haojie Wang, Zhichuan Li, Elizabeth Loreaux, Jerry B. Lingrel, Zijian Xie. “Regulation of Intracellular Cholesterol Distribution by Na/K-ATPase” J. Biol. Chem. Vol 284, No. 22, 14881-90, 2009. PMC2685670
   3. Yiliang Chen, Xin Li, Qiqi Ye, Jiang Tian,, Runming Jing, Zijian Xie. “Regulation of the α1 Na/K-ATPase Expression by Cholesterol” J. Biol. Chem. Vol 286, No. 17, 15517-24, 2011. PMC3083216
   4. “Materials and Methods Related to Sodium/Potassium Adenosine Triphosphate and Cholesterol” PCT patent application (US Patent: US20120289479 A1, date of patent: Jul. 3, 2014. PCT No. PCT/ US2011/ 021127)
2. CD36 and NKA function together to regulate macrophage responses to oxLDL.  Macrophages play a central role in atherosclerosis, as macrophage-derived foam cells are the major component of atherosclerotic plaques. My studies on macrophage biology have revealed that CD36/NKA complex is essential for foam cell formation and contributes to pro-inflammatory responses. I have also generated a novel mouse model and showed that CD36/NKA significantly contributes to the development of atherosclerotic plaque in vivo. These discoveries pave the way for further investigation of the pathophysiological role of CD36/NKA and their endogenous ligands in inflammatory diseases including atherosclerosis.
   1. David J. Kennedy, Yiliang Chen, Wenxin Huang, Jamie Viterna, Jiang Liu, Kristen Westfall, Jian Tian, David Bartlett, W. H. Wilson Tang, Zi-jian Xie, Joseph I. Shapiro and Roy L. Silverstein. “CD36 and Na/K ATPase-α1 Form a Pro-Inflammatory Signaling Loop in Kidney” Hypertension.Vol 61. 216-224, 2013.
   2. Yiliang Chen, David J. Kennedy, Devi Prasadh Ramakrishnan, Moua Yang, Wenxin Huang, Zhichuan Li, Zijian Xie, Alexandra C. Chadwick, Daisy Sahoo, Roy L. Silverstein. “Oxidized LDL-bound CD36 recruits a Na+/K+-ATPase-Lyn complex in macrophages that promotes atherosclerosis” Science Signaling, 8 (393): ra91, 2015.
   3. Yiliang Chen, Wenxin Huang, Moua Yang, Gang Xin, Weiguo Cui, Zijian Xie, Roy L. Silverstein. “Cardiotonic Steroids Stimulate Macrophage Inflammatory Responses Through a Pathway Involving CD36, TLR4, and Na/K-ATPase” Arteriosclerosis Thrombosis and Vascular Biology, 37(8), 1462, 2017
   4. Yiliang Chen, Moua Yang, Wenxin Huang, Wenjing Chen, Yiqiong Zhao, Marie L. Schulte, Peter Volberding, Zachary Gerbec, Michael T. Zimmermann, Atefeh Zeighami, Wendy Demos, Jue Zhang, Darcy A. Knaack, Brian C. Smith, Weiguo Cui, Subramaniam Malarkannan, Komal Sodhi, Joseph I. Shapiro, Zijian Xie, Daisy Sahoo, Roy L. Silverstein “Mitochondrial metabolic reprogramming by CD36 signaling drives macrophage inflammatory responses” Circulation Research, 125(12), 1087, 2019