Yiliang Chen, PhD

Yiliang Yiliang profile

Yiliang Chen, PhD

Assistant Investigator

Hemostasis, Thrombosis, and Vascular Bology

Assistant Professor of Medicine
Division of Endocrinology and Molecular Medicine
Medical College of Wisconsin

Education and Training

Postdoctoral Training
Blood Research Institute, Versiti Blood Center of Wisconsin (Silverstein Lab, Vascular Pathobiology)

Doctoral Training
Department of Physiology and Pharmacology (Zijan Xie Lab)
University of Toledo, Toledo, OH

M.S. National University of Singapore, Singapore
B.S. Biology, Fudan University, Shanghai

Contact Information

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.

Ongoing Research Support

09/01/2020-08/31/2023
Medical College of Wisconsin startup funding
Role: PI

04/01/2021-03/31/2025
“Pim1 kinase coordinates PPAR gamma pathway and mitochondrial function to mediate pro-atherogenic responses in macrophages” NHLBI, 1R01HL153397
Role: Co-Investigator

Completed Research Support

07/01/2017-06/30/2020          17SDG33661117                   
American Heart Association, Scientist Development Grant
“Na/K-ATPase-mediated signaling in the development of atherosclerosis”.
The goal of the study is to define mechanisms that antagonizing NKA signaling in vivo effectively reduce atherosclerosis.
Role: PI

Patents:

“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)

Jue Zhang, PhD
Postdoctoral Fellow

Yiqiong Zhao
Research Technician

Jackie Chang
Assistant Research Technician

  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. PMCID: PMC3521864
  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, 393:ra91, 2015. PMCID: PMC4852751
  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. PMCID: PMC5532064
  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. PMCID: PMC6921463
  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
 
Thrombosis & Hemostasis
We study the properties of blood that cause it to clot. Our findings help to treat diseases that cause blood clots or excessive bleeding.
 
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