Mohamed Oukka, PhD

Overview

Clinical Interests

Multiple Sclerosis, Lupus, Crohn's Disease, Cancer

Research Description

Professional History:
Dr. Oukka received his Ph.D. in Immunology at the University of Paris and Pasteur Institute (France) in 1997. Prior to joining the University of Washington and Seattle Children's Research Institute in 2009, he held positions at Brigham and Women's Hospital and Harvard medical School in Boston.

Research Description:
The adaptive immune system is required to clear pathogens. However, under specific conditions, T cells from the adaptive immune system are dysregulated, and attack the body's own tissues, leading to the development of autoimmune and graft versus host diseases. Autoimmune diseases represent a major threat to public health with >10 million Americans suffering from autoimmune disorders. Understanding how these diseases can be initiated and regulated is critical to the design of new therapeutics to treat autoimmune diseases.

Multiple Sclerosis is an autoimmune disease in which myelin is the target of an immune attack. It is believed that a subset of cells called regulatory T cells (Tregs) have a major function in preventing the auto-aggressive cells from attacking the self-myelin. What are these protective cells? How are they generated? How do they protect self-myelin from damage? These questions are the focus of my research. These Treg cells do not seem to work effectively in patients with MS. Treatment with ex vivo-generated Tregs has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of Treg in autoimmunity are not well understood. Our novel research model has considerably enhanced our understanding of how Tregs are generated in vivo and how they inhibit myelin damage. We have found that Tregs expand in the peripheral lymphoid compartment and readily accumulate in the central nervous system (CNS), but do not prevent the onset of disease. Tregs isolated from the CNS are effective in suppressing naive T cells, but fail to control CNS-derived encephalitogenic T cells that secrete IL-6 and TNF. Our data suggest that in order for Tregs to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.

Now we have ongoing studies focused on elucidating the specific mechanisms by which Tregs fulfill their suppressive function and identifying mechanisms by IL-6 produced during inflammation that inhibit Treg functions. The mechanisms that enhance and those that inhibit functions of Treg cells will have direct impact on developing potential immunomodulatory therapies for autoimmunity.

Early on in my carreer as molecular immunologist I was struck by people with MS and how their immune systems were attacking their own cells and organs. MS is so striking in young adults and such a debilitating disease. When a young mother has MS and is disabled, taking care of her own kids can be a challenge. MS really affects the whole family. I am interested in applied-science that leads to drug discoveries to help patients. If my research can make a difference in people's lives, for me that's the best reward.

Research Focus Area

Autoimmune Disorders, Immunology

Awards and Honors

Publications

Presentations