Jean-Luc Mougeot, Ph.D.

jean-luc.mougeot@atriumhealth.org

Education:

• 1989 B.S., Biochemistry, University Louis Pasteur, Strasbourg, France
• 1991 M.S., Cellular and Molecular Biology, University Louis Pasteur, Strasbourg, France
• 1995 Ph.D., Cellular and Molecular Biology, University Louis Pasteur, Strasbourg, France Professional

Experience:

• Master’s Program, Molecular and Cellular Biology, Université Louis Pasteur, Strasbourg, France 1989-1991
• Doctoral Scholar (MRT), Pararetrovirology and molecular biology, Université Louis Pasteur – CNRS, Strasbourg, France 1991-1995
• EMBO Post-doctoral Fellow, Pararetrovirology, Department of Plant Molecular Biology, Friedrich-Miescher Institute, Basle, Switzerland 1995-1997
• Senior Post-doctoral Fellow, AIDS Research Program – Medical Research Council – Laboratory of Molecular Biology, Cambridge, UK 1998-2000
• Director, Protein Science and Drug Discovery – deCODE Genetics, Inc., Reykjavik, Iceland 2000-2002
• Director, Molecular Biology Core Lab, Cannon Research Center, Carolinas Medical Center (CMC), Charlotte, NC 2002-2005
• Senior Scientist, Translational Research, Neurosciences Institute, Department of Neurology, CMC, Charlotte, NC 2005-2012
• Scientific Strategic Director, Department of Therapeutic Research and Development, CMC, Charlotte, NC 2012-2013
• Research Group Director, Translational Research, Department of Oral Medicine, CMC-Atrium Health, Charlotte, NC 2013-present

Research Interests:

Dr. Mougeot’s current research revolves around the discovery and characterization of human genomic and microbiomic biomarkers for the understanding and diagnosis of oral and systemic diseases and pathological conditions including rheumatic diseases (e.g., Sjögren’s syndrome), infective endocarditis (IE), and cancer therapy associated oral complications such as oral mucositis, radiation caries and periodontal disease. The team has also embarked upon research projects to determine genetic risk factors associated with COVID-19 severity. The lab utilizes next generation sequencing technology (targeted or genome-wide) for the analysis of microbial/viral metagenome and human genetic polymorphisms, as well as molecular methodologies and cell culture models for the functional characterization of candidate biomarkers. We also employ computational biology bioinformatics tools, including advanced text mining, to establish interactive knowledge-based databases. These databases will serve to characterize molecular interactions pertaining to disease pathophysiology and progression or interactions between the microbiome/virome and the host. These areas of research are relevant to drug discovery or repurposing of drugs and to the development of diagnostic tools. The lab studies genetic risk factors in cancer-therapy associate oral complications; biomarker discovery and functional characterization of Sjogren’s syndrome; oral microbiome and cardiovascular disease and cancer.

Genomics

• Genetic risk factors in cancer-therapy associated oral complications
• Oral complications occur frequently in head and neck cancer patients treated with radiation therapy (RT). We recently identified SNPs in collagen gene sets explaining periodontal disease progression following RT in patients with head and neck cancer, using exome sequencing. Patients with pre-RT periodontal disease who exhibited post-RT periodontal disease progression were characterized by SNPs predicted to exert a detrimental effect, within a collagen interaction/regulation network. Instead, patients with pre-RT periodontal disease who showed no progression post-RT were mainly characterized by SNPs in collagen interaction/regulation network, predicted to be beneficial.

Biomarker discovery and functional characterization

• Rheumatic Diseases (e.g., Sjögren’s syndrome)
• By combining text mining and molecular pathway analysis tools, we have established a knowledge-based gene expression database for Sjögren’s syndrome and related rheumatic diseases (i.e., rheumatoid arthritis and systemic lupus erythematosus) and identified LEF-1 and ETS-1 as novel significant pathogenesis biomarkers. We confirmed the overexpression of LEF-1 and ETS-1 in labial salivary gland (LSGs) biopsies by qRT-PCR, Western blot analysis and immunohistochemistry. In addition, we have demonstrated telomere instability in labial salivary glands and saliva DNA of Sjögren’s syndrome patients, possibly involving a mechanism mediated by LEF-1 which expression was highly correlated with that of the telomere maintenance gene ATM.

Microbiomics

• Oral microbiome and cancer therapy-associated oral complications
• We have determined oral microbiome profile changes characterizing hematological cancer HSCT patients who developed oral mucositis following conditioning therapy. We showed that for patients who developed ulcerative oral mucositis, the average relative abundance decreased for Haemophilus parainfluenza in oral samples, a species known as mucosal surfaces protector, but increased for Escherichia-Shigella genera. Our study concluded that post-conditioning oral mucositis might contribute to long-term oral microbiome changes mainly affecting Gammaproteobacteria, in HSCT patients.
• In another study, we investigated caries-associated oral microbiome profiles in head and neck cancer irradiation patients. In patients who developed caries post-RT, the average relative abundance of Prevotella melaninogenica was elevated, compared to those who did not. Prevotella melaninogenica is a bacterial species often associated with severe caries in young children which develop on smooth dental surfaces normally refractory to caries, similar to radiation caries. The average relative abundance of the health-associated species, Abiotrophia defective, decreased in the group who did not develop caries, while levels of Streptococcus mutans were similar to those of patients who developed caries. Overall, the oral microbiome underwent significant changes in radiation treated HNC patients, whether they developed caries or not. Thus, patients who develop caries might be more susceptible to certain species associated with oral disease or have fewer potentially protective oral species.
• Cardiovascular diseases
• We are investigating the conditions and mechanisms by which IE-associated species within the microbial sub-communities in oral cavity promote bacteremia and hence increase the risk for IE. A better understanding of these mechanisms can be achieved in part by comparing patients who underwent antibiotic prophylaxis (AP) to those who did not. Ultimately, treatment strategies limiting the use of AP which may lead to the emergence of antibiotic resistance, including IE-associated species, may be developed.
• We have also provided evidence that Porphyromonas gingivalis is the most abundant species detected in clinically healthy coronary and femoral arteries of patients with cardiovascular disease. The detection of 229 species besides P. gingivalis suggests the involvement of oral pathogens in predisposing to cardiovascular disease.

Publications:

Genomics

• Talevi V, Wen J, LalIa RV, Brennan MT, Bahrani Mougeot F, Mougeot JC. Identification of SNPs associated with periodontal disease in head and neck cancer irradiation patients by exome sequencing. Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology 2020