NEW YORK, NY (October 3, 2016) -- Researchers at Columbia University College of Dental Medicine (CDM) Columbia University Medical Center (CUMC) have identified 41 master regulator genes that may cause gum disease, also known as periodontal disease. The study was the first of its kind to employ genome-wide reverse engineering to identify the gene pathways that contribute to periodontitis.
Identification of the genes represents a vital step toward developing compounds that can be used in targeted, individualized treatment of severe periodontitis, before loss of teeth and supportive bone occurs.
Findings of the study were published recently in the Journal of Dental Research.
In gene expression studies, investigators find those genes that are most commonly expressed in either healthy or diseased tissue. But such studies cannot identify a causal link between these genes and the disease, and often miss genes that affect a larger number of genetic pathways, which may have a large impact on the disease process.
In this study, a team led by Panos N. Papapanou, DDS, PhD, professor and chair of oral, diagnostic and rehabilitation sciences at the College of Dental Medicine at CUMC, "reverse-engineered" the gene expression data to build a map of the genetic interactions that lead to periodontitis and identify individual genes that appear to have the most influence on the disease. "Our approach narrows down the list of potentially interesting regulatory genes involved in periodontitis," says Dr. Papapanou. "This allows us to focus on the handful of genes that represent the most important players in the process rather than the whole transcriptome."
To identify the genes, Dr. Papapanou partnered with CUMC investigators in Systems Biology who had previously developed algorithms to identify regulatory genes that fuel cancer growth. The researchers examined RNA from healthy and diseased gum tissues of 120 patients with periodontitis.. They applied one algorithm to study the interactions among the genes and used another algorithm to identify genes that disrupt healthy tissue and drive the disease process.
Many of the genes identified by Dr. Papapanou and his team are implicated in immune and inflammatory pathways, confirming laboratory and clinical observations of the development of periodontal disease.
Identification of the master regulator genes will allow investigators to test compounds that interrupt their action, creating treatments that stop periodontal disease at its source. "Now it's important to do the downstream work of validating these master regulators in the lab before we can test these genes in experimental models," says Dr. Papapanou.
The paper is titled, "Identification of Master Regulator Genes in Human Periodontitis." The other contributors are A.D. Sawle (CUMC), M. Kebschull (CDM), and R.T. Demmer (CUMC),
The authors declare no financial or other conflicts of interests.
The study was supported by grants from the National Institutes of Health/National Institute of Dental and Craniofacial Research (DE015649, DE021820, DE024735) and by an unrestricted gift from Colgate-Palmolive Inc.
Columbia University College of Dental Medicine, among the first university-affiliated dental schools in the United States, was founded in 1916. As part of a world-class medical center, the school trains general dentists and dental specialists in a setting that emphasizes the interconnection between oral health care and overall health for both individuals and communities. The school supports research to advance personalized, evidence-based oral health care and contribute to the professional knowledge base for future oral health leaders. In its commitment to service learning, the school provides dental care to underserved communities of Northern Manhattan and also engages in dental care and local oral health care capacity-building initiatives abroad. Its faculty has played a leadership role in advancing the inclusion of oral health programs in national health-care policy and has developed novel programs to expand oral care locally and in developing countries. For more information, visit dental.columbia.edu.
Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.