Özlem Yilmaz, D.D.S., Ph.D.

Associate Professor of Periodontology and Oral Biology

College of Dentistry and the Emerging Pathogens Institute

2014 Awardee

Özlem Yilmaz studies host-bacteria interaction in the oral cavity and periodontal diseases.

Yilmaz investigates colonization mechanisms of an opportunistic pathogen, Porphyromonas gingivalis, using an in-vitro human primary gingival epithelial model and systems biology approach. P. gingivalis is a successful colonizer of oral mucosa and a major etiological agent in severe forms of periodontitis, which has recently been identified as a risk factor for a number of serious chronic diseases. Her current focus is on both basic and translational patient-oriented research to enhance understanding of the persistent bacterial infections (particularly P. gingivalis) in human mucosal tissues by examining specific host and bacterial molecular factors.

Within the gingival crevice, epithelial cells embody an initial defense to invading oral microbes and also serve as an initial site as well as primary reservoir for microbial colonization. Yilmaz’s earlier work was the first to characterize the gingival epithelial cell receptor for P. gingivalis attachment and internalization into human gingival epithelial cells. She carried out original studies on invasion/survival mechanisms of P. gingivalis in gingival epithelium, which lead to the seminal finding that the organism can block apoptotic cell death through multiple mechanisms and spread within the gingival epithelium in a specialized way. These studies were extended in her laboratory to identify a novel multi-functional secreted effector (a homolog of Nucleoside-Diphosphate-Kinase ‘NDK’) from P. gingivalis that is required for suppression of host cell death and critical for increasing the organism’s ability to persist in gingival epithelium. NDKs are a highly conserved family of proteins recently implicated in cancer etiology, metastasis, metabolic homeostasis, epithelial morphogenesis, and bacterial persistence.

In conjunction with those findings, her work also demonstrated that the infection by P. gingivalis induces accelerated cell proliferation. This was an initial study demonstrating a possible molecular link between chronic infections by P. gingivalis and development of oral cancers. In addition, her laboratory is a pioneer in genetic fluorescence-protein labeling of obligate-anaerobic bacteria for studying host-bacteria interaction, and designing novel flow-cytometry and imaging approaches to examine intracellular bacterial life.

Yilmaz’s laboratory revealed for the first time that epithelial cells express purinergic P2X<sub>7</sub> receptors, so-called “danger signal receptors.” P2X<sub>7</sub> receptor signaling emerged lately as a critical determinant for controlling persistent infections, modulating host cell death, and immune response in immune cells. Her studies currently focus on characterizing P2X<sub>7</sub>/ATP signaling in epithelial cells as a key physiological modulator of host cell response, including oxidative stress, chronic inflammation, and intracellular infections.