The lymphatic system plays an important role in how blood vessel diseases develop. It helps control immune responses, move cholesterol out of tissues, and manage inflammation.  

Our lab studies how the growth of new lymphatic vessels (lymphangiogenesis) and swelling around blood vessels (perivascular inflammation) relate to natural anti-inflammatory signals in the body. 

We also are identifying and characterizing the proteins and pathways that regulate mRNA stability in vascular smooth muscle cells. By learning how manipulation of these proteins can help diseases like atherosclerosis and restenosis, we hope to find better ways to protect blood vessels and improve health. 

We are studying the roles of endothelial cells, vascular smooth muscle cells, macrophages, and regulatory T cells in the progression of cardiovascular disease (CVD), chronic kidney disease, diabetes, respiratory disease and other forms of inflammation. We are employing cutting-edge "omics” approaches in immunometabolism and epigenetics to aid in these discoveries. These include metabolomics, epigenomics, transcriptomics, chromatin long range interaction and organelle interactions.

The heart contains a complex network of lymphatic vessels that are essential for draining interstitial fluid from heart tissue and helping the immune system keep the heart healthy. Cardiac lymphatics have emerged as a potential therapeutic target for promoting cardiac function after ischemic heart disease. Research in our lab focuses on understanding the development and the function of cardiac lymphatics in cardiovascular disease. Our goal is to develop novel approaches for treating cardiovascular disease.

Learn more about our lab.

Our lab focuses on: 

• How leukocytes migrate from tissues to lymph nodes via lymphatic vessels during inflammation and immune responses. 
• The role that vascular endothelial cells play in leukocyte trafficking through the lymphatic system. 
• How the lymphatic system affects lipid transport in obesity and insulin resistance. 
• How obesity and diabetes impact the function of the lymphatic system of different adipose tissue. 

Our lab studies blood vessel conditions like restenosis (when arteries narrow again after treatment) and aortic aneurisms (dangerous bulges in the main artery from the heart). These conditions can be life-threatening, so better treatments are needed. 

We focus on a special type of cell in blood vessel walls called vascular smooth muscle cells (VSMCs). These cells help form the structure of the vessels and react to changes in their environment. In disease, they can change their behavior, a process called phenotypic modulation. Our research aims to understand exactly how and why these changes happen, so we can learn how to stop or reverse them. 

In addition, our team published an exciting discovery in Circulation. We found a new RNA gene, which we called INKILN. It has no protein function and only works in its RNA form. The discovery of INKILN helps us better understand how blood vessel disease happens, leading to new treatments. 

The Wei Laboratory investigates how protein quality control pathways in the endoplasmic reticulum (ER) regulate metabolism and contribute to human disease. Our research focuses on ER-associated degradation (ERAD), a highly conserved protein quality control mechanism that eliminates misfolded, damaged, or excess proteins to maintain cellular homeostasis. Dysregulation of ERAD has been implicated in a wide range of metabolic, inflammatory, and degenerative diseases.

A major focus of our laboratory is understanding the physiological and pathological functions of the ERAD E3 ubiquitin ligases MARCHF6 and HRD1. We recently demonstrated that MARCHF6 serves as a critical regulator of hepatic lipid homeostasis by targeting the lipogenic transcription factor SREBP1 for ER-associated degradation, thereby protecting against metabolic dysfunction-associated steatotic liver disease (MASLD) (Journal of Hepatology, Xu et al., 2026).

In studying hepatic proteotoxic stress responses, we discovered a previously unrecognized adaptive pathway linking ER stress to epitranscriptomic regulation. We found that the m6A RNA methyltransferase METTL14 mediates stress-induced mRNA methylation to promote cellular adaptation to ER proteotoxic stress, a mechanism we termed the “ER proteotoxic stress–m6A pathway” (ERm6A) (Molecular Cell, Wei et al., 2021). Our work has also uncovered important metabolic functions of HRD1 beyond its established role in ERAD. We demonstrated that HRD1 directly ubiquitinates metabolic enzymes to regulate hepatic metabolism and obesity development. In addition, we identified HRD1 as a key regulator of the hepatokine FGF21 through polyubiquitination of the transcription factor CREBH, thereby controlling systemic metabolic homeostasis (Nature Communications, Wei et al., 2018; EMBO Journal, Wei et al., 2018; Molecular Metabolism, Kim et al., 2018).

By integrating molecular biology, metabolism, proteomics, and mouse genetics, our laboratory seeks to define how ER protein quality control pathways coordinate cellular and organismal metabolism and to identify new therapeutic strategies for metabolic and liver diseases.

The primary research goals in the Yu laboratory are to understand the molecular control of vascular pathophysiology (arterial, venous, and lymphatic). We have used mouse genetics, cell biology, and biochemistry intensively to achieve these goals. Currently, our major efforts are directed at:

1. Novel signaling molecules that regulate atherogenesis and late atherosclerotic plaque necrosis using tissue-specific conditional knockout mouse models.

2. Lymphagiogenesis and lymphatic remodeling. Uncovering novel signaling molecules and ER remodeling mechanisms that govern lymphangiogenesis and lymphatic vessel integrity under pathological conditions, eg, myocardial infarction, secondary lymphedema, and diabetes.

3. Defining the role of mitogen-activated protein kinase phosphatase (MKP) in arteriovenous fistular (AVF) maturation. atherosclerosis and ischemic cardiomyopathy. We are currently examining the causal role of MKP-5 in AVF maturation in end-stage renal disease and establishing a novel nanoparticle approach for cell-specific targeting to promote AVF maturation.

4. Molecular control of vascular remodeling. Identify novel signaling pathways that regulate ischemia-induced collateral remodeling, angiogenesis, and neointimal hyperplasia, particularly in patients with metabolic disease.

5. The role of reticulon in the regulation of autophagy and vascular inflammation. We are investigating how the functional ER protein controls autophagic flux to regulate inflammation. Understanding the mechanisms of autophagosome formation and the regulation of inflammation may shed light on the development of new strategies for treating inflammation-related diseases, including atherosclerosis and diabetes.

The Xu Laboratory investigates the molecular mechanisms that drive vascular inflammation and atherosclerosis, with a particular focus on how lipid signaling pathways regulate endothelial dysfunction and cardiovascular disease progression. Our research integrates vascular biology, immunology, metabolism, and multi-omics approaches to identify novel therapeutic targets for cardiometabolic diseases. A major focus of our work is understanding how bioactive lipids and G protein-coupled receptors (GPCRs) modulate vascular inflammation. We have identified the lysophosphatidylinositol (LysoPI)-GPR55 signaling pathway as a key regulator of endothelial activation and atherosclerotic lesion development. Using genetically engineered mouse models, primary vascular cells, transcriptomics, metabolomics, and functional vascular analyses, we seek to define how lipid-mediated signaling networks contribute to chronic vascular inflammation.

Our laboratory is also interested in the emerging field of immunometabolism and the role of cellular stress responses in vascular disease. Current studies investigate how mitochondrial dysfunction, metabolic reprogramming, and inflammatory signaling influence endothelial and lymphatic endothelial cell function during atherosclerosis, chronic kidney disease, and Myocardial Infarction. By combining mechanistic studies with systems-level analyses, our goal is to uncover fundamental pathways linking metabolism and inflammation and to translate these discoveries into new therapeutic strategies for cardiovascular and inflammatory diseases.