Grant supports twin research
From September/October 2005 Psoriasis Advance
Brian J. Nickoloff, M.D., Ph.D., professor and associate chairman of pathology at Loyola University of Chicago, recently received a five-year grant from the National Institutes of Health to study psoriasis and twins. We asked Dr. Nickoloff about his research.
How long have you been studying psoriasis?
I have been conducting research on psoriasis for the past 20 years. A leading psoriasis authority, Dr. Eugene Farber, chair of the Department of Dermatology at Stanford University, encouraged me to use my background in biochemistry and immunobiology to find a cure for this enigmatic disease.
What will you do with the grant funding?
We're using a unique mouse model to understand psoriasis development in identical twins — why one twin will develop psoriasis but the other will not.
Brian Nickoloff, M.D., Ph.D
|
|
We know that symptomless skin from a psoriasis patient (in this case a twin), when transplanted to this mouse model, will spontaneously form psoriasis. Skin from a patient without psoriasis does not result in psoriasis when transplanted to this mouse. We are asking: What happens when skin from an identical twin that has not developed psoriasis is transplanted to this mouse? Are there specific cells in the twin with psoriasis that can cause psoriasis to develop? Are there cells that can suppress psoriasis development in the twin who does not have psoriasis? Once we identify specific cells involved in psoriasis development, we will study how these cells are activated and regulated.
Can you elaborate on your work?
Our research will involve collaboration with my former post-doctoral fellow and current colleague, Dr. Frank Nestle, as well as several colleagues here in Chicago. This competitive renewal is focused on defining the immunopathogenesis of psoriasis — how the immune system is altered and causes psoriasis. We have developed two mouse model systems to study psoriasis. In these animal models, skin from psoriasis patients is grafted (transplanted) onto mouse skin. Under normal circumstances, the immune system would recognize the graft as a foreign object and reject it, but these mice are immunosuppressed so they will not reject the graft. There are two different models — one uses a SCID mouse (lacking B and T cells — important immune cells), and the other uses an AGR mouse (immunosuppressed by lacking genes critical to the development of the immune system).
Can you tell us more about the AGR mouse model?
This model allows one to ask the question if specific skin has the potential to develop psoriasis. This question (or hypothesis) can be tested by transplanting skin onto the AGR mouse.
How did you become interested in studying twins?
We realized we have a model to test if specific skin will develop into psoriasis and that we could use this model to explore psoriasis development in identical twins. We know that although twins are identical and have the same DNA, one may get psoriasis while the other does not. In other cases, they both have psoriasis, but the psoriasis develops at different times or with different severity. We know that there is a genetic component to psoriasis, so why is it that in some cases both twins do not develop psoriasis? And if they do develop psoriasis, why is it that their psoriasis is different? With our model system, we can graft symptomless skin from both twins onto different AGR mice and ask questions we were unable to study in the past.
What specific questions will these studies help you answer?
Will skin from both twins produce psoriasis when grafted to mice? We expect the symptomless skin from the twin with psoriasis to produce psoriasis on the AGR mouse. What will happen with the skin from the twin who does not have psoriasis? If it does not produce psoriasis, this leads to additional questions we can study.
We could use this system to help us identify and isolate a cell type responsible for psoriasis. For example, what if we injected cells from the twin who has psoriasis into the AGR mouse grafted with symptomless skin from the twin without psoriasis? Could we get that skin to produce a psoriasis lesion? Once the cell responsible for psoriasis development is identified, we can study how this cell is activated and regulated. We also will identify and study genes involved in the life cycle of this cell.
Finally, we want to understand if there are cells in the twin without psoriasis that may be responsible for stopping psoriasis development. We could test this by injecting cells from the twin without psoriasis into the mouse grafted with symptomless skin from the twin with psoriasis. If these suppressor cells exist, we would expect this mouse would not develop psoriasis.
Are you interested in studying fraternal twins?
We are also interested in studying fraternal twins. Their DNA is not identical, so there may be some technical issues, but we are interested in understanding psoriasis development in fraternal twins.
More and more research is being conducted on monozygotic (identical) twins, not only from the autoimmune perspective, but also to learn more about the susceptibility to developing cancer and many other diseases. It is becoming clear that identical twins lose many similarities as they get older, indicating the need to study gene regulation.
What is your goal?
This work will likely be applied to developing new treatments for psoriatic patients and to better define the role of genes in the cause of psoriasis. I hope within the next five years that we can indeed find the cause and cure for this skin disease.
|
