BBSP Faculty

We are interested in determining the mechanisms involved in the beneficial modulation of the gut microbiota by prebiotics (functional foods that stimulate growth of gut native beneficial bacteria) and probiotics (live bacteria that benefit their host). Specifically, we aim to develop prebiotic and probiotic interventions as alternatives to traditional treatments for microbiota-health related conditions, and to advance microbiota-based health surveillance methods.

Our long-term goal is to define the molecular mechanisms of two-component regulatory systems, which are utilized for signal transduction by bacteria, archaea, eukaryotic microorganisms, and plants. Our current focus is to identify and understand the features that control the rates of several different types of protein phosphorylation and dephosphorylation reactions. The kinetics of phosphotransfer reactions can vary dramatically between different pathways and reflect the need to synchronize biological responses (e.g. behavior, development, physiology, virulence) to environmental stimuli. Member of the Molecular & Cellular Biophysics Training Program.

My lab is focused on the improvement of treatment of chronic bacterial infections. We aim to determine the mechanisms of antibiotic tolerance. Our aim is to understand the physiology of the bacterial cell, primarily Staphylococcus aureus, during infection and how this physiology allows the cell to survive lethal doses of antibiotic. We will use advanced methods such as single cell analysis and Tn-seq to determine the factors that facilitate survival in the antibiotic’s presence. Once we understand this tolerance, we will develop advanced screens to identify novel compounds that can be developed into therapeutics that can kill these drug tolerant “persister” cells and eradicate deep-seated infections.

Dr. Cotter’s research is aimed at understanding molecular mechanisms of bacterial pathogenesis. Using Bordetella species as models, her group is studying the role of virulence gene regulation in respiratory pathogenesis, how virulence factors activate and suppress inflammation in the respiratory tract, and how proteins of the Two Partner Secretion pathway family are secreted to the bacterial surface and into the extracellular environment. A second major project is focused on Burkholderia pseudomallei, an emerging infectious disease and potential biothreat agent. This research is aimed at understanding the role of autotransporter proteins in the ability of this organism to cause disease via the respiratory route.

Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease. In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.

We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.

My lab studies a recently identified pathogen-sensing signaling complex known as the inflammasome. The inflammasome is responsible for the proteolytic maturation of some cytokines and induces a novel necrotic cell death program. We have found that critical virulence factors from certain pathogens are able to activate NLRP3-mediated signaling, suggesting these pathogens may exploit this host signaling system in order to promote infections.  Our lab has active research projects in several areas relating to inflammasome signaling ranging from understanding basic molecular mechanisms of the pathway to studying the role of the system in animal models of infectious diseases.

Our research focuses on the discovery and design of new gene-encoded bioactive small molecules from bacteria.  We are interested in understanding enzymes involved in their biosynthesis, their therapeutic mechanisms of action, and implications in health and diseases, in particular with respect to the human microbiome.  This work is driven by intensive development of new metabolomics and genomics technologies.  We subsequently manipulate and engineer these biosynthetic pathways to make new and improved molecules as potential therapeutics such as antibiotics.

Traditionally, basic science has sought to enter the translational pipeline through what can be referred to as “Bottom-Up” science, that is, studies that start with a hypothesis in the lab and aim to develop clinical relevance of the findings. In some cases, notably in conventional antibiotic development, this has worked well – but it assumes one-size fits all solutions that are only as good as our assumptions about the biology of many infectious diseases such as tuberculosis. By contrast, my research focuses on a “Top-Down” approach, leveraging the power of bacterial population genomics to identify bacterial processes important for Mtb success in people and to then employ cutting-edge experimental techniques to mechanistically dissect these processes with the goal of leveraging them using new translational tools.

In my work to date, I have applied this “Top-Down” strategy to define bacterial determinants of treatment outcomes and transmission success, as evident in first-author/corresponding author publications in prestigious journals such as Science, Nature Ecology Evolution, Cell Host Microbe, Science Advances, Genome Biology, PNAS, etc. My work combines expertise in evolutionary biology and bacterial genomics, cutting-edge bacterial genetics and high-throughput experimental phenotyping.

In my own lab, I will use these tools to (1) define the biological mechanisms that enable Mtb to survive antibiotic treatment; (2) identify bacterial determinants of TB transmission success; and (3) elucidate the evolutionary mechanisms underlying the emergence of new bacterial pathogens.

Molecular genetic analysis of virulence of Yersinia and Klebsiella: My laboratory uses Yersinia enterocolitica, Y. pestis, and Klebsiella as model systems to study bacterial pathogenesis. The long-term goals of our work are to understand the bacteria-host interaction at the molecular level to learn how this interaction affects the pathogenesis of infections and to understand how these pathogens co-ordinate the expression of virulence determinants during an infection. To do this we use genetic, molecular and immunological approaches in conjunction with the mouse model of infection.

My laboratory has two main interests: 1) Regulation of P2Y receptor signaling and trafficking in epithelial cells and platelets. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of polarized epithelial cells and the regulation of P2Y receptor signaling during ADP-promoted platelet aggregation. 2) Antibiotic resistance mechanisms. We investigate the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporins. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.

We are interested in unraveling the molecular basis for human disease and discover new treatments focused on human and microbial targets. Our work extends from atomic-level studies using structural biology, through chemical biology efforts to identify new drugs, and into cellular, animal and clinical investigations. While we are currently focused on the gut microbiome, past work has examined how drugs are detected and degraded in humans, proteins designed to protect soldiers from chemical weapons, how antibiotic resistance spreads, and novel approaches to treat bacterial infections. The Redinbo Laboratory actively works to increase equity and inclusion in our lab, in science, and in the world. Our lab is centered around collaboration, open communication, and trust. We welcome and support anyone regardless of race, disability, gender identification, sexual orientation, age, financial background, or religion. We aim to: 1) Provide an inclusive, equitable, and encouraging work environment 2) Actively broaden representation in STEM to correct historical opportunity imbalances 3) Respect and support each individual’s needs, decisions, and career goals 4) Celebrate our differences and use them to discover new ways of thinking and to better our science and our community

Our lab uses a systems biology approach to study phenotypic heterogeneity in bacteria. We develop tools that quantify single cell bacterial transcription. We then compare dynamic measurements during vegetative growth and infection to identify regulators of gene expression and mechanisms that bacteria use to coordinate community organization. With this data we want to understand the role of heterogeneity and noise in infectious disease.

Our long term goals are to better define mechanisms of chronic intestinal inflammation and to identify areas for therapeutic intervention. Research in our laboratories is in the following four general areas: 1) Induction and perpetuation of chronic intestinal and extraintestinal inflammation by resident intestinal bacteria and their cell wall polymers, 2) Mechanisms of genetically determined host susceptibility to bacterial product,. 3) Regulation of immunosuppressive molecules in intestinal epithelial cells and 4) Performing clinical trials of novel therapeutic agents in inflammatory bowel disease patients.

The Singleton Laboratory is interested in understanding the molecular basis for the develoment and transmission of microbial drug resistance and the discovery and exploitation of new strategies for controlling drug-resistant microorganisms. We develop and adapt synthetic chemistry and synthetic biology methods to provide new molecular tools — both biologically active small molecules and innovative platforms — for hypothesis-driven biological research and pharmaceutical discovery. These foundations of our program offers both chemically-oriented and biologically-oriented researchers new opportunities for the development of integrated, multi-disciplinary knowledge and technologies.

Our lab studies the mechanisms facultative pathogens use to adapt to disparate and changing extracellular conditions. Our primary interest is in the ability of Vibrio cholerae, the causative agent of cholera, to persist in its native aquatic environment and also flourish in the host intestinal tract. We are addressing key questions about the role of cyclic diguanylate, a signaling molecule unique to and ubiquitous in bacteria, in the physiological adaptations of V. cholerae as it transits from the aquatic environment into a host. In addition, we are identifying and characterizing factors produced by V. cholerae during growth in a biofilm, a determinant of survival in aquatic environments, that contribute to virulence.  I will be accepting rotation students beginning in the winter of 2009.

By 2035, more than 500 million people worldwide will be diagnosed with diabetes. Individuals with diabetes are prone to frequent and invasive infections that commonly manifest as skin and soft tissue infections (SSTIs). Staphylococcus aureus is the most commonly isolated pathogen from diabetic SSTI. S. aureus is a problematic pathogen that is responsible for tens of thousands of invasive infections and deaths annually in the US. Most S. aureus infections manifest as skin and soft tissue infections (SSTIs) that are usually self-resolving. However, in patients with comorbidities, particularly diabetes, S. aureus SSTIs can disseminate resulting in systemic disease including osteomyelitis, endocarditis and sepsis. The goal of my research is to understand the complex interactions between bacterial pathogens and the host innate immune response with focus on S. aureus and invasive infections associated with diabetes. My research is roughly divided into two project areas in order to understand the contributions of the pathogen and the host response to invasive infections associated with diabetes. Project 1: Defining mechanisms of immune suppression in diabetic infections. Project 2: Determine the role of bacterial metabolism in virulence potential and pathogenesis.

I am a clinical/translational researcher in Infectious Diseases. I am the Director of the Immunocompromised Host Program – which provides ID care to patients with transplants, malignancies, and burns. My primary research interests are antibacterial resistance in gram-negative bacilli, and infections in vulnerable patients. I am the PI for the Carbapenem Resistance Consortium for Klebsiella and other Enterobacteriaceae (CRACKLE) and PI for the Multi-Drug Resistant Organism (MDRO) Network. I am also supported by NIAID to evaluate community origins of carbapenem-resistant Enterobacterales.

We are interested in understanding how autoreactive B cells become re-activated to secrete autoantibodies that lead to autoimmune disease.  Our research is focused on understanding how signal transduction through the B cell antigen receptor (BCR) and Toll Like Receptors (TLR) lead to secretion of autoantibodies in Systemic Lupus Erythematosus (SLE).

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for a variety of diseases in individuals with compromised immune function. Dr. Wolfgang’s research focuses on the pathogenesis of Pseudomonas aeruginosa infection.  The goal of his research is to understand how this opportunistic pathogen coordinates the expression of virulence factors in response to the host environment. Projects in his laboratory focus on the regulation of intracellular cyclic AMP, a second messenger signaling molecule that regulates P. aeruginosa virulence. Dr. Wolfgang’s laboratory uses a combination of molecular genetics and biochemical approaches to understand how P. aeruginosa controls the synthesis, degradation and transport of cAMP in response to extracellular cues. Other related projects focus on the regulation and function of P. aeruginosa Type IV pili (TFP). TFP are cAMP regulated surface organelles that are critical for bacterial colonization of human mucosal tissue. In addition, the Wolfgang lab is actively involved in characterizing the lung microbiome of patients with chronic airway diseases and studying the interactions between P. aeruginosa and other bacterial species during mixed infections.