Yorgo Modis, PhD
Yale University, New Haven, CT
The blueprint for what makes us each unique—DNA and RNA—is carried inside the nucleus of each of our cells. Normally, our immune systems deftly distinguish our own DNA and RNA from that of foreign invaders such as viruses and bacteria.
But in people with lupus, the immune system reacts to its own DNA and RNA as if these blueprint “chips” were the enemy that required extermination. What prompts these cases of misidentification? Tantalizing research indicates that proteins called Toll-Like Receptors (TLRs), which normally recognize DNA and RNA only from infectious pathogens such as viruses, may be to blame.
Dr. Modis is among the LRI researchers who have a novel idea for uncovering more about the role of TLRs in lupus.
By creating highly detailed three-dimensional models of TLR proteins bound to DNA and RNA, he will be able to observe how the receptors transmit their “on” signals to the immune system. These intricate models also offer possible ways to design drugs that interfere with, and stop, the alert signals that trigger such devastation in lupus.
A ligand-binding pocket in the dengue virus envelope glycoprotein. Modis Y, Ogata S, Clements D, Harrison SC. (2003) Proc Natl Acad Sci USA 100:6986-91.
X-ray structure of a protein-conducting channel. Van den Berg B, Clemons Jr WM, Collinson I, Modis Y, Hartmann E, Harrison SC, Rapoport TA. (2004) Nature 427:36-44.
Structure of the dengue virus envelope protein after membrane fusion. Modis Y, Ogata S, Clements D, Harrison SC. (2004) Nature 427:313-9.
Crystal structure of West Nile virus envelope glycoprotein reveals viral surface epitopes. Kanai R, Kar K, Anthony K, Gould LH, Ledizet M, Fikrig E, Marasco, WA, Koski RA, Modis Y. (2006) J Virol 80:11000-8.
In 2007, Dr. Modis won a 7-year, $500,000 grant from the Burroughs Wellcome Fund (Investigators in the Pathogenesis of Infectious Disease Award) to continue the work that he began with his LRI funding.
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- B Cells
- Cardiovascular System
- Cell Signaling
- Central Nervous System
- Dendritic Cells
- Environmental Triggers
- Gender Matters
- General Immune System Function
- Human Lupus Biology
- Lupus Pregnancy
- New to Lupus
- New Treatments
- T Cells
- Target Identification
- Why the Lupus Immune System Reacts to Its Own DNA