Research funding for OHSD faculty
Congratulations to our OHSD faculty on another successful year in obtaining funding for their ongoing research projects.
Richard J. Lamont, PhD, Professor. The Lamont lab studies both bacteria-bacteria and bacteria-host interactions. Many bacterial infections are polymicrobial in nature, and synergistic interactions among the participating bacteria result in elevated virulence of the entire community. Within that context, the lab investigates: the structure/function of interbacterial adhesins that allow coadhesion among community members and stabilize community structure; the signal transduction pathways that allow bacteria to adapt to a community environment and facilitate community development; and the modulation of virulence gene expression that impacts overall pathogenicity. Host epithelial cells provide a physical barrier to microbial intrusion and also an interactive interface that signals the presence of bacteria to the underlying immune cells. The Lamont lab is engaged in the study of bacterial manipulation of host epithelial cell signaling pathways to impede innate immune responses. Additionally, modulation of cell cycle and cell death pathways, that could have relevance to cancer development, is under investigation. The responses of human trophoblasts to oral bacteria, that have relevance to the maintenance of pregnancy, are also being studied. The lab is also involved in an ambitious project to integrate transcriptomic, proteomic and metabolomic data to define the host-bacterium interface. This project involves collaborators at the University of Washington, Northeastern University, and Osaka University, Japan.
Supported by NIH grants DE11111, DE12505, DE17921, DE22867, DE16690, DE23193
Douglas Darling, PhD, Professor. In the oral cavity the first line of defense is saliva, and the lack of salivary proteins (due to radiation therapy or Sjogren’s Syndrome) allows rampant oral infections. Parotid Secretory Protein (PSP) was recently shown to be a highly abundant protein in saliva, with antibacterial and anti-fungal activity. The Darling lab has defined the ability of PSP to bind to rare lipids in bacterial membranes. Separately, the lab has studied the role of the transcription factor Zeb1 in development and cancer. Zeb1 is an essential effector of embryonic development and cellular differentiation. Zeb1 is also critical in driving the transition of tumor cells into a metastatic phenotype. The lab is defining the pattern of expression of Zeb1 during the progression of human oral epithelial dysplasia into highly undifferentiated oral cancer. This work is well integrated with the focus on cancer at the UofL.
Supported by NIH grants DE19243, DE22679
Donald R. Demuth, PhD, Professor. The Demuth lab is engaged in the discovery of novel compounds to prevent colonization of pathogenic bacteria. Using Click Chemistry, the lab is designing small molecules that mimic the binding domains of bacterial proteins responsible for attachment to other bacteria and to oral surfaces. These molecules are being tested in animal models for their activity in preventing bacterial colonization and reducing or eliminating bacterially induced disease. The lab also investigates inter-species signaling based on soluble mediators, and is actively seeking means to disrupt the bacterial cross-talk that is necessary for pathogenic community development.
Supported by NIH grants DE14605, DE23206, DE12505
Shuang Liang, PhD, Assistant Professor. The Liang lab is investigating immunological mechanisms in pregnancy-associated periodontal disease. The regulation of infection-induced regulatory T-cell (Treg) development in periodontitis by pregnancy hormones, and the effect of this regulation on pregnancy-associated periodontal disease, is the primary objective. The lab has also designed and synthesized nanoparticles carrying therapeutic peptides that block inflammatory-based tissue destruction. These are being tested in animal models for the inhibition of pathogen-induced inflammation and bone loss.
Jan Potempa, PhD, professor. The Potempa lab is a world leader in study of the biogenesis and functionality of bacterial proteases. The lab has unraveled a novel secretion system that exports these proteases, the components of which are attractive targets for novel therapeutic agents. They have also defined antigenic tags that oral bacteria add to host proteins resulting in autorecognition by the immune system, and potentially contributing to rheumatoid arthritis.
Supported by NIH grants DE9761, DE22597
David A. Scott, PhD, Associate Professor. There are two major areas of research in the Scott lab, both related to how tobacco promotes oral and systemic diseases. The first is to investigate the mechanisms by which immune cells respond to nicotine. Pathways activated by nicotine impact the signaling that normally serves to recognize and respond to bacterial challenge. This work will lead to a better understanding of how nicotine increases susceptibility to oral and systemic diseases. The second area of focus examines how tobacco-gene interactions modify oral bacterial antigenicity, dramatically altering immune recognition. This research has relevance to multiple infectious inflammatory conditions that are either exacerbated by periodontal diseases or share risk factors, such as vascular diseases.
Support by NIH grants DE17680, DE19826
Huizhi Wang, MD, PhD, Assistant Professor. The Wang lab is interested in host inflammatory responses which are triggered by oral bacteria and control host innate immune status. Such responses can be protective and serve to constrain the bacterial challenge, or destructive through the mistimed and misdirected production of potentially toxic intermediates and immune effectors. In particular, the lab studies signal transduction pathways and transcription factors in innate immune cells that regulate inflammatory cytokine production. Inhibition or interference with these pathways is a potential avenue to ameliorate the severity of inflammatory diseases.
Supported by NIH grant DE23633