Dr. L. Jeannine Brady Laboratory
Work in the Brady Lab is directed at understanding mechanisms of membrane and cell surface biogenesis in the cariogenic pathogen Streptococcus mutans. The functional interactions and respective roles of components of the co-translational signal recognition particle (SRP) pathway and the YidC1 and YidC2 chaperone-insertases in membrane protein insertion are being evaluated with an emphasis on competence development and mutacin production. In addition, S. mutans has been found to produce functional amyloids that influence biofilm development and that can serve as targets for therapeutic amyloid-modifying compounds. Study is currently directed at elucidating the structural basis and environmental control of amyloid fibrillization in in vitro and in vivo systems. Furthermore, S. mutans is capable of releasing DNA into the extracellular environment via membrane vesicles. The contribution of vesicle-released eDNA to biofilm formation and its functional interactions with bacterial cells and extracellular matrix components are under study. Post-doctoral candidates will be considered to evaluate protein translocation systems in S. mutans as related to virulence attributes and potential therapeutic targets, or to evaluate development and stabilization of biofilm matrices related to amyloid formation. Candidates should have demonstrated expertise in standard molecular biology techniques, protein expression and purification methodologies, and characterization of protein-protein and protein-nucleic acid interactions, or in protein structure analysis (particularly by solid state NMR), and/or in electron and confocal microscopy.
Dr. Frank C. Gibson III Laboratory
The Gibson lab is interested in defining novel host pathogen interactions that influence the progression of anaerobic bacterial disease. Our lab has longstanding interest in defining host immunologic sensing of the periodontal disease pathogen Porphyromonas gingivalis as a model organism from which to understand the chronic inflammation and tissue destruction that characterizes periodontal disease. We routinely combine immunologic, molecular, microbiologic, vaccine, and animal modeling approaches in our studies. New areas of interest in the laboratory include detailing the contribution of microbial sphingolipids in both cellular and oral infection.
Dr. Nadeem Khan Laboratory
Our laboratory investigates how inflammatory pathways at mucosal surfaces, particularly in the lungs and oral cavity, determine whether immune responses remain protective or become drivers of pathology. A major focus of our program is on respiratory infections such as influenza and Streptococcus pneumoniae, both individually and as co-infections, which represent leading causes of morbidity and mortality worldwide. In the past few years, our lab has made seminal discoveries that have significantly advanced the field of respiratory immune responses, including identifying how CD8⁺ T cells, monocytes, and other immune cell subsets interact with cytokine networks, transcriptional regulators, and immune-stromal pathways to shape host defense, tissue repair, and the transition to pathogenic inflammation in the respiratory tract. We use cutting-edge in vivo transgenic mouse models and single-cell and systems-level approaches to define the mechanisms by which immune pathways are diverted toward tissue injury during respiratory bacterial and viral infections. The long-term goal of our research is to develop a mechanistic framework that can guide interventions to reduce pathogenic inflammation while maintaining antimicrobial defense at mucosal surfaces.
In addition to mechanistic studies of host-pathogen interactions, our laboratory is also dedicated to translational research aimed at developing new preventive strategies. Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis worldwide, and current vaccines are limited by serotype coverage and waning effectiveness. To address this critical gap, we are focused on designing a serotype-independent pneumococcal vaccine that overcomes the shortcomings of existing polysaccharide and conjugate-based approaches. Recently, we developed a protein-based vaccine that has demonstrated remarkable protective efficacy in preclinical animal models. Building on these promising results, our goal is to advance this platform toward clinical translation, with the long-term vision of providing broad and durable protection against pneumococcal disease.
Dr. Jose Lemos & Dr. Jacqueline Abranches Laboratory
The Lemos-Abranches lab uses genetics, biochemistry, transcriptomic and metabolomics approaches to characterize the molecular factors that mediate virulence in opportunistic Grampositive pathogens such as Streptococcus mutans and Enterococcus faecalis. In S. mutans, a major pathogen in dental caries and a leading causative agent of infective endocarditis, our current efforts focus on the characterization of the oxidative stress regulator Spx and its role in controlling stress responses and biofilm formation. The second S. mutans project focuses on the characterization of a collagen binding protein responsible for intracellular invasion of heart and oral tissues, a trait that is linked to increased virulence and, potentially, recurrent infection and chronic inflammation. The characterization of stress responses is also the theme of our research with E. faecalis, a leading cause of hospital-acquired infections. In this project, we are investigating the interplay between the stringent response, a major bacterial stress response mechanism for adaptation to changing environments, with other prominent stress regulators and how these interactions influence the ability of E. faecalis to survive antibiotic stress and other adverse conditions.
Dr. Luis Martinez Laboratory
The Martinez lab is interested in elucidating the mechanisms of central nervous system (CNS) invasion by the encapsulated and AIDS-associated fungus Cryptococcus neoformans and the interactions of the fungus with cells of the CNS including microglia, astrocytes, and neurons. We approach our research in an interdisciplinary manner, post-doctoral fellows that join the lab will be trained on basic microbiology, microscopy, immunological and tissue culture techniques, neuroscience and behavioral techniques, molecular biology, antimicrobial research, and animal models of infection. (Project number: R01 AI1455592)
Dr. Bernadett Papp Laboratory
We investigate how human cells respond to oncogenic viral infections on a genome-wide scale and identify novel mechanisms that control the outcomes of these viral infections. To this end, we focus on uncovering novel host-pathogen interactions during viral infections. By identifying the key transcription factors, epigenetic regulators, and signaling pathways that govern cell fate changes and host-pathogen interactions, we aim to uncover novel therapeutic targets.
Dr. Ann Progulske-Fox Laboratory
The Progulske-Fox lab is focused on the molecular mechanisms of the pathogenesis of Porphyromonas gingivalis (P. gingivalis), an anaerobic bacterium that is associated with adult periodontitis and recently reported to be involved in various systemic diseases like cardiovascular disease, rheumatoid arthritis, aspiration pneumonia, and Alzheimer’s disease. Bacterial species in general have evolved multiple mechanisms to survive ecological, nutritional and chemical stresses as well as host cell defenses. Among these is to enter a viable but non-culturable (VBNC) state. The ability of a bacterial species to enter the VBNC state and also resuscitation from this state is now recognized to be an important or even required mechanism for the survival and pathogenesis of several bacterial pathogens, especially those that are associated with chronic infections. Studies in the lab are designed to genetically and metabolically characterize the VBNC state and resuscitation from the VBNC state of the oral pathogen, P. gingivalis. (NIH award number: R01DE028656). Candidates should possess demonstrated expertise in molecular biology techniques such as cloning and the creation of mutants and should have experience using in vitro cell biological systems for the study of bacterial infections.
Dr. Robert Shields Laboratory
The Shields lab investigates the genetics and physiology of oral streptococci, focusing on the primary microbial cause of tooth decay, Streptococcus mutans. Our central mission is to uncover the fundamental processes that allow these bacteria to survive and thrive. Our research employs both traditional and modern methods including next generation sequencing, proteomics, electron microscopy, forward genetics (transposon sequencing), CRISPR technologies and fluorescence microscopy. We are actively working (RO1DE033403) on understanding how mobile genetic elements, that may spread antimicrobial resistance or virulence traits, transfer among oral bacteria. Another of our current efforts in S. mutans is on generating an arrayed mutant library and using this library to find genes that are important for biofilm formation (a key virulence trait) (R15DE034550). In another project, we have been characterizing how protein phosphorylation networks regulate essential processes like cell division and metabolism. Through our multi-faceted approach, we hope to generate critical insights into the biology of S. mutans, paving the way for innovative strategies to control this significant human pathogen.
Dr. Zsolt Toth Laboratory
Our research focuses on Kaposi’s sarcoma–associated herpesvirus (KSHV), one of the seven known human oncogenic viruses. We aim to elucidate the molecular mechanisms that regulate lifelong KSHV infection. Using systems biology, viral genetics, and structural–functional biochemical approaches, we investigate how viral and host factors control primary infection, latency establishment, and lytic reactivation. These studies are conducted in several physiologically relevant cell types—including B cells, epithelial cells, and endothelial cells—that serve as natural targets for KSHV infection. We have identified multiple novel cellular factors and viral mechanisms that play key roles in promoting KSHV infection by modulating epigenetic regulation, cellular signaling pathways, and protein stability. Our studies were the first to demonstrate that environmental stressors such as hypoxia and specific bacterial byproducts can profoundly influence KSHV infection outcomes, including viral production and dormancy. By uncovering the fundamental drivers of KSHV infection under different physiological stress conditions, we aim to enable the development of new therapeutic strategies to prevent chronic infection and KSHV-associated cancers.
Dr. Shannon Wallet Laboratory
The Wallet Laboratory’s research interests are focused on mechanisms associated with altered innate immune functions, which lead to dysregulated inflammation and adaptive immunity. As such, our program has four major arms integrated through a central philosophy. Specifically, our laboratory focuses on the contribution of epithelial cell biology and signaling to innate and adaptive immune homeostasis and dysfunction. We study the contribution of what I term ‘epithelial cell innate immune (dys)function’ to four major disease conditions: periodontal disease, chronic wounds, oral mucosal melanoma and pancreatic cancer.
While appearing to be a diverse research program, we have found that many of the mechanisms and systems in play are surprisingly (or maybe not so surprisingly) similar, allowing for rapid translation of our findings. Importantly, previous investigations into the role of epithelial cells in immunobiology have been hindered by a lack of robust primary cell culture techniques, which our laboratory has been able to overcome using both animal and human tissues. Thus, using our novel and unique tools we can evaluate our findings in the human conditions, again making translation of our findings that much more feasible.
In addition to the primary research objectives, we have a very collaborative research program, which has allowed us to be involved, at some level, in investigating the basic biology of health, multiple autoimmune conditions, autoinflammation, muscle biology in inflammation and cancer, sepsis, and burn/inhalation injury.
Our laboratory is home to very talented staff scientists as well as all levels of trainees including undergraduates, DMD students, PhDs, and post-docs where we collaboratively work to move science forward in meaningful ways. I have been blessed with the opportunities to couple my passions and expertise with that of others to bring together multiple research communities with the goal of advancing human health and hope to be able to continue to do so for years to come.
Dr. Lin Zeng Laboratory
The main interest of the Zeng group is in bacterial metabolic activities in oral microbiome, including a multitude of carbohydrates, amino acids, and their respective metabolic products. We use conventional and cutting-edge, multi-omics techniques of Microbiology, Molecular Genetics and Genomics to explore the influence of these compounds on microbial homeostasis and virulence of the dental biofilms. Understandings achieved at the molecular level can then be applied in the design of novel therapeutics such as pre- and pro-biotics to enhance human oral health. We welcome motivated students and trainees to join the lab!