Research

Role of MG53/TRIM72 in Aging-Induced Muscle Atrophy

This project aims to understand the function of MG53/TRIM72 as a myokine in protecting muscle satellite cells during aging-induced muscle atrophy. MG53/TRIM72 is a protein known for its role in cell membrane repair and has been implicated in various physiological processes, including muscle repair and regeneration. Understanding its specific role in protecting muscle satellite cells could provide insights into potential therapeutic interventions for age-related muscle degeneration.

The therapeutic effectiveness of using combination of rhMG53 and CitH3 antibody on flu virus induced multiple organ failure in aged population

The worldwide human population continually faces the challenge of seasonal influenza and other aggressive respiratory virus infections, especially for aged population. A therapeutic approach that mitigates virus-induced inflammation is urgently needed to treat multi-organ failures. We are now examine the therapeutic effectiveness of using rhMG53, CitH3 antibody, and their combination on flu virus induced multiple organ failures, and further establish the dosing and timing strategies for the systematic administration of rhMG53 and/or CitH3 in mouse model, so that we can establish the prophylactic and therapeutic windows for ameliorating virus-induced multi-organ failures.

Finding a novel druggable target for diabetes

Obesity is a complex and chronic disease that affects more than a 30% of the world’s population. Changes in lifestyle, particularly increased consumption of unhealthy diets, are thought to be major causes of the current epidemic of obesity and type 2 diabetes (T2D). T2D, about 90-95% of people with diabetes, is characterized by insulin resistance. Due to numerous dietary factors and dietary supplements that could contribute to modulating insulin signaling, it is challenging to identifying specific diet-derived factor(s) that contribute to modulating insulin signaling.

Mitsugumin 29 (MG29, also known as SYPL2) belongs to a synaptophysin-family-related protein that located in the junction between the plasma membrane (PM) and sarcoplasmic reticulum (SR) of skeletal muscle. Several reports have implicated single nucleotide polymorphisms in SYPL2 as high-risk factors for metabolic dysfunction in obesity and diabetes. We found that MG29 facilitates the translocation of Glut4-containg vesicles in myoblasts upon insulin stimulation. This process is essential for glucose uptake in skeletal muscle cells.

Skeletal muscle is one of the largest organs of glucose consumption in the body. The ability for muscles to uptake circulating blood glucose is primarily modulated by glucose transporters such as GLUT1 and GLUT4. As one of the largest sites of glucose deposition in the body, increasing skeletal muscle sensitivity to insulin remains a promising avenue for treatment of type 2 diabetes.

In muscles cells, MG29 is necessary for insulin-stimulated glucose uptake, and it can increase glucose uptake in other cells as well. MG29 and Glut4 have been found in the same intracellular vesicles, suggesting a correlation between the two proteins. Composition modulating MG29 has been proposed for use in the treatment of diabetes, as they can improve glucose uptake in skeletal muscle cells.

Treatment of Diabetic ulcer through novel molecule theropy

Diabetic Foot Ulcer (DFU) is mainly contributed by developed neuropathy and damaged blood circulation issue in diabetic patients. There are statistics shown that 60% of diabetic patients will develop DFU. DFU can lead to infection, amputation, and death. Currently, we are facing an urgent treatment needs for its related treatments. Elevated NETosis levels have been identified as a contributing factor to impaired wound healing and amputation risk in DFU patients. Citrullinated histone H3 (CitH3) plays a critical role in initiating NETs (Neutrophil Extracellular Traps)- induced immune cell death and tissue injury. We have successfully developed a humanized anti-CitH3 antibody (hCitH3-mAb) with higher binding capabilities to CitH3 than the commercially available antibodies. Our proposal aims to create a topical delivery system for hCitH3-mAb, enabling sustained release for the treatment of diabetic ulcers.

Effect of MG53 on induced neuroinflammatory M1 (TNF-A, LPS, IFN-Y) and M2 (IL-4) markers in HMC3 cells in vitro

 We are investigating the attenuating impacts of MG53 on neuroinflammation in the brain along the TLR4/NF-kB pathway based on M1 and M2 macrophage markers (i.e. iNOS and CD206). The M1 marker is associated with the tissue damage phenotype, and its level may be elevated by Tumor Necrosis Factor Alpha (TNF-A), lipopolysaccharide (LPS), and Interferon Gamma (IFN-Y). The M2 marker is associated with tissue repair and Interleukin 4 (IL-4). MG53 may have the protective effect of inducing M1 to M2 polarization, a potential therapeutic effect for neuroinflammation tied to Alzheimer’s Disease. We are attempting to understand the role of microglial cells, the brain’s primary immune cells, in this neuroinflammatory pathway using the Human Microglial Clone 3 (HMC3) cell line. 

Mechanism of Netosis in Sterile Inflammation

 This project focuses on exploring the mechanism of netosis, a process where neutrophils release DNA traps to capture and kill pathogens, in sterile inflammation. Sterile inflammation refers to inflammatory responses triggered by tissue damage or injury rather than infection. By understanding the mechanisms underlying netosis in sterile inflammation, the goal is to identify ways to mitigate excessive inflammation and prevent the cytokine storm that often occurs after injury, which can exacerbate tissue damage. 

The therapeutic effectiveness of MG53 in acute myocardial injury and stress-induced chronic heart failure

Cardiovascular disease is the leading cause of death in developed countries, and effective therapeutic interventions reducing cardiovascular mortality are still limited. The central focus of our laboratory is to identify the potential mechanisms responsible for heart injury, and finally lead to therapeutic treatment of patients with heart diseases. We are currently workin on several research directions in order to identify new therapeutic targets (MG53, lncRNA CAMIRT, lncRNA Ael1, etc.) using animal models of heart failure induced by different stresses, including myocardial ischemia/reperfusion, virus-inudced myocarditis, chemotherapy drugs, and aging.

MG53 in Inflammatory Bowel Disease (IBD) 

This work revolves around a cutting-edge project that delves into the intricate world of intestinal health and its relationship with various health conditions. Specifically focused on Inflammatory Bowel Disease (IBD) employing a DSS-induced colitis model to simulate the inflammatory response within the intestine, a significant aspect of this research centers on understanding the dynamic interplay between the microbiome – the diverse community of microorganisms in the gut – and the development of intestinal disorders. As part of an innovative approach, this studying seeks to utilize a probiotic engineered to secrete MG53, a membrane repair protein. This unique strategy aims to explore the therapeutic potential of MG53 in mitigating intestinal damage and promoting overall gut health. The multifaceted nature of this project not only contributes to our understanding of intestinal physiology but also holds promise for the development of novel therapeutic interventions. Explore the exciting realms of intestinal science and innovative probiotic research with this project!

MG53 as a myokine in the development and progression of cancer

Over the past decades, tramendous efforts have been made to fight against cancer in the world. The use of chemotherapy medicine remains one of the most successful options. However, studies have shown that the extensive use of the chemotherapy agents leads to multidrug resistance and the toxicity to the other vital organs. one of our ongoing projects is to elucidate the role of MG53 as a myokine in the progression of pancreatic cancer.

Investigation of citH3 Antibody Therapy for Sepsis

Sepsis, a life-threatening condition resulting from the body’s overwhelming response to infection, remains a significant global health concern with high mortality rates despite advances in medical care. Neutrophil extracellular traps (NETs), composed of chromatin and antimicrobial proteins, play a crucial role in the immune response against pathogens. However, in certain conditions such as sepsis, excessive NET formation can lead to tissue damage and organ dysfunction. Citrullinated histone H3 (citH3), a hallmark component of NETs, has emerged as a potential therapeutic target in sepsis due to its involvement in inflammatory processes and tissue injury. This research project aims to explore the therapeutic potential of citH3 antibody in the management of sepsis. The study will delve into the fundamental mechanisms underlying the role of citH3 in sepsis pathogenesis, focusing on its contribution to inflammatory responses, endothelial dysfunction, and organ damage. By elucidating the intricate interplay between citH3 and immune dysregulation in sepsis, this research seeks to provide insights into the development of novel treatment strategies targeting NET-mediated pathology.

Investigation of TRIC-A in Nuclear Ca²⁺ Regulation, Chromatin Repositioning, and Their Implications for Emery-Dreifuss Muscular Dystrophy