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; Jul;130(1):32-42.e4.
• Mougeot JC, Noll B, Bahrani-Mougeot FK. Sjögren's Syndrome X-chromosome dose effect: an epigenetic perspective. Oral Diseases 2019; Mar;25(2):372-384.
• Brennan MT, Mougeot JL. Alu retroelement-associated autoimmunity in Sjögren's syndrome. Oral Diseases 2016; Jul;22(5):345-7.
• Mougeot JL, Bahrani-Mougeot FK, Padilla RJ, Brennan MT, Lockhart PB. Use of archived biopsy specimens to study gene expression in oral mucosa from chemotherapy-treated cancer patients. Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology 2013; May;115(5):630-7.
• Baciu C, Thompson KJ, Mougeot JL, Brooks BR, Weller JW. The LO-BaFL method and ALS microarray expression analysis. BMC Bioinformatics 2012; 13:244.
• Mougeot JL, Bahrani-Mougeot F, Lockhart PB, Brennan MT. Microarray analyses of oral punch-biopsies from AML patients suggest immune deregulation and DNA damage as a likely prerequisite for chemotherapy-induced oral mucositis. Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology 2011; 112(4):446-52.
• Mougeot JL, Li Z, Price EA, Wright FA, Brooks BR. Microarray analysis of peripheral blood lymphocytes from ALS patients and the SAFE detection of the KEGG ALS pathway. BMC Medical Genomics 2011; 4:74.
• Mougeot JL, Milazi-Richardson S, Brooks BR. Whole-genome association studies of sporadic amyotrophic lateral sclerosis: are retroelements involved? Trends in Molecular Medicine 2009; 15(4):pp148-58.
• Gruber HE, Mougeot JL, Hoelscher G, Ingram JA, Hanley EN. Microarray analysis of laser capture microdissected-annulus cells from the human intervertebral disc. Spine 2007; 32(11): pp1181-1187.
• Mougeot JL, Bahrani-Mostafavi Z, Vachris JC, McKinney KQ, Gurlov S, Naumann RW, Higgins RV, Hall BJ. Gene expression profiling of ovarian tissues for determination of molecular pathways reflective of tumorigenesis. Journal of Molecular Biology 2006; 258(1): pp310-329.

Biomarker discovery

• Noll B, Bahrani Mougeot F, Brennan MT, Mougeot JC. Telomere erosion in Sjögren's Syndrome: A multi-tissue comparative analysis. Journal of Oral Pathology & Medicine 2019; Jan;49(1):63-71.
• Shah NR, Noll B, Padilla RJ, Brennan MT, Mougeot FKB, Mougeot JL. Expression of ETS1 and LEF1 in salivary glands of Sjögren’s Syndrome patients. Oral Diseases 2019; Jan;25(1):164-173.
• Kirk J, Shah N, Noll B, Stevens CB, Lawler M, Mougeot FB, Mougeot JC. Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy. Supportive Care in Cancer 2018; Aug;26(8):2695-2705.
• Shah NR, Noll BD, Stevens CB, Brennan MT, Mougeot FB, Mougeot JL. Biosemantics guided gene expression profiling of Sjögren’s Syndrome: A comparative analysis with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Research and Therapy 2017; 19(1):192.
• Mougeot JL, Hirsch MA, Stevens CB, Mougeot FB. Oral biomarkers in exercise-induced neuroplasticity in Parkinson’s disease. Oral Diseases 2016; Nov;22(8):745-753.
• Lee JG, McKinney KQ, Mougeot JL, Bonkovsky HL, Hwang S. Proteomic strategy for probing complementary lethality of kinase inhibitors against pancreatic cancer. Proteomics 2013; Dec;13(23-24):3554-62.
• Marshburn PB, Zhang J, Bahrani-Mostafavi Z, Mostafavi BZ, Mougeot JL, Roshon M. Estrogen receptor-alpha mRNA variants lacking exon 5 or exon 7 are co-expressed with wild type form during all stages of human endometrial development. American Journal of Obstetrics and Gynecology 2004; 191: pp626-634.
• Leclerc D, Burri L, Kajava AV, Mougeot JL, Hess D, Lustig A, Kleemann G and Hohn T. The open reading frame III product of cauliflower mosaic virus forms a tetramer through a N-terminal coiled-coil. Journal of Biological Chemistry 1998; 273 (44), 29015-29021.
• Mougeot JL, Guidasci T, Wurch T, Lebeurier G and Mesnard JM. Identification of C-terminal amino acid residues of cauliflower mosaic virus open reading frame III protein responsible for its DNA-binding activity. Proceedings of the National Academy of Sciences USA 1993; 90, 1470-1473.

Microbiomics

• Mougeot J-LC, Beckman MF, Almon KG, Morton DS, von Bültzingslöwen I, Brennan MT, Mougeot FB. Lasting Gammaproteobacteria profile changes characterize hematological cancer patients who developed oral mucositis following conditioning therapy. Journal of Oral Microbiology 2020; May 13;12(1):1761135.
• Mougeot JC, Stevens CB, Almon KG, Paster BJ, Lalla RV, Brennan MT, Mougeot FB.
• Caries-associated oral microbiome in head and neck cancer radiation patients: a longitudinal study. Journal of Oral Microbiology 2019; Mar 8;11(1):1586421
• Mougeot JC, Stevens CB, Morton DS, Brennan MT, Mougeot FB. Oral Microbiome and Cancer Therapy-Induced Oral Mucositis. Journal of the National Cancer Institute Monographs 2019; Aug 1;2019(53).
• Mougeot JL, Stevens CB, Paster BJ, Brennan MT, Lockhart, PB, Mougeot FB. Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries. Journal of Oral Microbiology 2017; 9(1):1281562.
• Mougeot JL, Stevens CB, Cotton SL, Morton DS, Krishnan K, Brennan MT, Lockhart PB, Paster BJ, Mougeot FB. Concordance of HOMIM and HOMINGS technologies in the microbiome analysis of clinical samples. Journal of Oral Microbiology 2016; Apr 8;8:30379.
• Napeñas JJ, Brennan MT, Coleman S, Kent ML, Noll J, Frenette G, Nussbaum ML, Mougeot JL, Paster BJ, Lockhart PB, Bahrani-Mougeot FK. Molecular methodology to assess the impact of cancer chemotherapy on the oral bacterial flora: a pilot study. Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology 2010; 10 (4): 554-60.
•