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Local Researcher Dr. Deyu Fang Discusses Current Project on New Target to Reduce Disease Development and Allow Natural Repair in Multiple Sclerosis

Last October, funds from the Illinois State Lottery helped launch eight innovative local MS research projects which range from investigating the reduction of disease development and stimulation of myelin repair to original rehabilitation and physical exercise techniques. To get a better understanding of the research happening statewide, Greater Illinois Chapter marketing staff interviewed the lead researcher overseeing each pilot project.   

Dr. Deyu Fang is one of the National MS Society’s grant recipients for 2013. Dr. Fang received his Ph.D. from Gunma University School of Medicine in Molecular Virology in 2000. Currently, Dr. Fang is an Associate Professor in the Department of Pathology at the Feinberg School of Medicine at Northwestern University, researching the molecular networks in the regulation of immune response and autoimmunity.

Q: First, tell me a little about yourself. What led you into the world of MS research and how did you get to the point you are at now?

A: I grew up in China, and because of the Chinese system, I did medical school as an undergraduate. In China, you go straight into a professional school right out of high school. I chose medical school because my mom wanted me to be a medical doctor. During my fifth year, I spent 100 percent of my time in the hospital, and in that moment I realized I actually didn’t want to be a medical doctor. Emotionally, I found it very, very difficult to see a patient sick. I then decided to go into research to still contribute to human health. I got a master’s degree in pharmacology and after three years I felt I better understood the science behind drug development and decided to choose a really significant health problem to focus my attention on. I chose inflammation and immune disorders, of which multiple sclerosis is one example. I then went to Japan to complete my Ph.D. and in 2000 came to this country to work at a post doc at La Jolla Institute for Allergy and Immunology in San Diego. After three years, I realized I wanted to specifically investigate the reasons behind why some people have healthy, normal immune systems while others have immune systems that act against themselves.

Q: So your research specifically deals with autoimmune diseases?

A: Yes. Basically inflammation autoimmune disease is a consequence of the immune system, which is supposed to protect the self against foreign influences such as bacteria or virus infection, instead acting against the self. In arthritis, in multiple sclerosis, the problem is that the immune system is acting against the self. So my research deals with trying to figure out what the difference is between the people whose immune systems guard their bodies versus the people whose immune systems turn on themselves. And I’m interested at looking for these differences at the molecular level, at looking inside the cell to determine the problem. This key to understanding immune tolerance, the process by which the immune system knows when not to attack, is still locked inside the cell and my lab is using both mouse genetic models and human samples to unlock the answers.

Q: You were given a grant that was funded by the Illinois State Lottery to study a new target to reduce disease development in MS. Can you explain in more detail what this research focuses on?

A: This particular project funded by the National MS Society is looking at a particular gene of interest that we found may be related to multiple sclerosis. I collected blood samples from both healthy individuals and from individuals with MS and compared the gene expression profiles. Most researchers seem to be looking at which genes are upregulated, and I was surprised to find that during the past 50 years no one really focused on which genes are downregulated. It is common to assume reduction isn’t important, or at least isn’t as important as escalation. However, sometimes reduction can be very important. So we looked at both the upregulated and downregulated genes in patients. We found a lot of interesting upregulated genes, but many of these genes had already been discovered. However, we can reproduce the results of these publications, which is important. But, what is really exciting is that we discovered a gene that was downregulated in individuals with MS. We are currently researching the effect that this downregulated gene may have on the development of autoimmune disease.

Q: Why do people assume reduction is not as important as escalation?

A: In theory, many times even a 50 percent reduction of a certain function doesn’t matter. We have two kidneys – remove one and you’re still alive. Close one eye and you still see fairly well out of the other. Cover one ear, you can still hear out of the other. In these cases, and many more, a 50 percent reduction isn’t a big deal, and that’s why people tend to ignore it.

Q: Have you tested the effects of downregulating this gene?

A: We started using mice to investigate this gene. If we get rid of 50 percent of this gene expression in mice, what will happen? When we genetically manipulated the expression of this gene in mice and removed about 50-70 percent of the gene expression, the mice start to get sick and develop inflammation. So I think that proves that this gene is important. When we delete or only partially express this gene in mice, in particular in T cells, in lymphocytes, we can cause multiple sclerosis.

Q: What is the significance of this study with regard to a novel multiple sclerosis therapy?

A: The goal of the National MS Society, and the goal of everyone in this field, is to discover the novel therapy for multiple sclerosis. This discovery suggests that if we, by whatever means, can reconstitute the function of this gene, we can potentially treat the disease or protect people from the disease. I think this is the significance of this study. We are currently measuring how easily our mice can get the disease or how resistant they are to getting sick. If the mice are more resistant to the disease, we look at why. We are doing a lot of molecular biology and genetic studies to answer this question. Our goal, to figure out the mystery which has not been figured out during the last half century, that is, which genes are important in MS, is pretty big. But I’m hopeful.

Q: Many MS researches are focusing their efforts on improving on quality of life while waiting for a cure to be discovered. As a medical doctor turned researcher, what do you say to that?

A: Relieving symptoms is important, of course, but that’s what a doctor is for. A doctor tries to provide ways to relieve symptoms without getting to the underlying cause of the problem. If you can re-craft the reason beneath the problem, you can probably treat the disease. I’m trying to get at the root of multiple sclerosis.

Q: Do you think gene therapy has the potential to be a future MS therapy?

A: The problem with multiple sclerosis is that we still don’t understand what causes the disease. Even in other autoimmune diseases, there are so many factors. Whether gene therapy will be an option for all kinds of autoimmune diseases depends on whether the disease is a consequence of a single gene mutation. If it is, yes gene therapy could be possible. And although we don’t know the cause, at this stage we don’t think multiple sclerosis is caused by a single gene. If a disease is caused by multiple genes, gene therapy is very, very difficult. However, it is possible that if there is a most critical gene for multiple sclerosis, and we discover it, let’s call this gene “X,” we can either raise X to a normal level or suppress X to a normal level. First we just need to find “X.” Hopefully this gene I discovered is “X,” and if this gene is suppressed in MS patients as our findings might suggest, it is relatively easy to get “X” back to a normal level.

Q: Have other studies been done on this particular gene?

A: This gene is fairly new. If you look at PubMed, you will see fewer than 10 publications on this gene, and none of them relate to inflammation. My lab is the first to look at this gene as it relates to multiple sclerosis. This is exciting because we have already proven that this gene is important in the mouse model of multiple sclerosis. If we suppress this gene in the mouse, the mouse gets sicker. Whether this gene is the most important affecter to multiple sclerosis, or just a contributor, we don’t know get. It’s too early to make a conclusion, but that’s what we’re figuring out. I myself get excited by the research. Of course my mom is a little disappointed that I didn’t stick with medical school. My mom asks me “what are you doing?” and I say I’m working with mice, and she says “Oh! You are still an M.D. – a mouse doctor!”

Q: What are your thoughts on the next decade of MS research?

A: I am optimistic. I am more optimistic than others because personally I see the progress and improvement in the entire world of biomedical research, including multiple sclerosis. The first reason is that technology is improving and becoming increasingly accessible. Gene analysis is cheap and efficient. Only about 10 to 15 years ago, when I was a graduate student, comparing genes was so inefficient and expensive, but today you can analyze many, many genes at once at a relatively affordable price. The second reason is that not only is technology improving, but our entire scientific understanding is progressing. The entire human genome database is freely available. Whether we can completely cure multiple sclerosis, I do not know. But I am very optimistic about the fact that we will see a much greater understanding of the underlying mechanisms of this disease, and that may lead to a cure.

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