Pei-Hui Lin, Ph.D., is a Principal Research Associate in Dr. Jianjie Ma's laboratory in the Department of Physiology and Biophysics at UMDNJ-Robert Wood Johnson Medical School. Dr. Lin works on translational research of cell membrane repair and calcium signaling in health and diseases. Dr. Ma's research team works on different aspects of cell and molecular biology in muscle physiology, aging, cardiovascular disease, and cancer treatment. Dr. Lin was involved in the initial discovery of MG53 as a membrane repair gene in 2008. This discovery led to using recombinant MG53 to modulate therapeutic cell membrane repair in regenerative medicine.
An emerging concept in recent biomedical research establishes that intrinsic membrane repair is a fundamental aspect of normal physiology and that disruption of this repair function underlies the progression of many human diseases. Mitsugumin 53 (MG53) is an essential component of the cell membrane repair machinery. Our data present MG53 protein as an attractive biological reagent for restoration of membrane repair defects in human diseases.
What did you set out to discover with your research?
Throughout the lifecycle, injury to the body's cells occurs naturally, as well as through trauma. Cells have the ability to repair and regenerate themselves, but a defect in the repair process can lead to cardiovascular, neurological, muscular or pulmonary diseases. We were interested in understanding the basic biology for repair of damage to the cells and tissues, and in further translating our basic findings into therapeutic applications of human diseases. A few years ago, our laboratory discovered that MG53 is an essential gene for assembly of the cell membrane repair machinery (Cai et al, Nature Cell Biology 11(1): 56-64, 2009.) We found that MG53 can rapidly move to the acute injury sites to patch the injured cell membrane. Genetic ablation of MG53 led to defects in tissue repair and progression of muscular and cardiovascular dysfunctions. In this study we examined the translational value of targeting MG53 function in tissue repair and regenerative medicine.
What were your most significant findings?
Several of our findings suggest that MG53 could be translated into a treatment for use in human patients to target cell membrane repair in regenerative medicine. We show that serum levels of MG53 could be used as a biomarker to detect physiological and pathophysiological changes in muscle structure, such as those associated with muscle injury or diseases of the striated muscles. Because the native MG53 protein is present in the circulating blood, the risk that systemic delivery of recombinant MG53 protein would produce immunogenic or toxicological effects is minimized. In all of our studies, we used the human MG53 protein to establish that the human sequence was successful at increasing membrane resealing. The fact that recombinant human MG53 (rhMG53) protein can be effectively produced in microorganisms or mammalian cells that are widely used in bioprocess development also simplifies the translation of these findings into human patients.
We studied the use of rhMG53 protein in treating muscular dystrophy by targeting the protein directly to the damaged muscle. The direct application of MG53 slowed the development of the disease by repairing damaged muscle membranes. Our data support the concept of targeting cell membrane repair in regenerative medicine, and present MG53 protein as an attractive biological reagent for restoration of membrane repair defects in human diseases.
Were these findings surprising?
The findings are surprising and exciting.
The most surprising aspect of this study was the high efficacy that the recombinant MG53 protein in repairing tissue damage when applied outside the cells and tissues. While we already knew that MG53 played an essential role in tissue repair based on several of our published studies we were surprised that rhMG53 could be used directly as a therapeutic approach.
What are the potential implications of your findings?
Our results show that MG53 has potential to be used in treatment of muscular dystrophy. Since muscular dystrophies currently have limited treatment options, this could represent a major advance in addressing this unmet medical need. In addition, our findings indicate rhMG53 could be useful in treatment of other disease states where compromised membrane integrity contributes to the disease pathology. So our finding could lead to the development of pharmaceutical treatments for diseases such as myocardial infarction (heart attacks), ischemic stroke and lung disorders.
What is the next step for your research?
Before clinical trials using rhMG53 in human patients could begin, additional studies are needed to be completed. These include pre-clinical studies such as additional safety tests and production of MG53 protein that can be used in human patients as a therapeutic drug.
These are Dr. Pei-Hui Lin's written remarks. Please refer to the video interview for exact quotes.
Related Research Papers
Recombinant MG53 Protein Modulates Therapeutic Cell Membrane Repair in Treatment of Muscular Dystrophy
Press release: Protein repairs cell damage in muscle dystrophy