University of Pennsylvania and Children's Hospital of Philadelphia
The human gastrointestinal tract is home to a rich collection of microorganisms that has been termed the gut microbiota. This community of bacteria, fungi, archaea, and viruses is essential for our health and provides us nutrients, aids in digestion, primes our immune system, and confers colonization resistance to invading pathogens. In addition to keeping us healthy, the gut microbiota has also been associated with numerous diseases including obesity, Inflammatory bowel disease, and cancer. The field of microbiome research has made significant strides over the past decade, primarily powered by the rapid advancement of next generation sequencing technologies, but our understanding of mechanisms that drive microbiota-associated diseases remains limited.
Our goal is to understand how interactions between the host, gut microbiota, and pathogenic microbes impact human health and disease. At the center of our research is the important nosocomial pathogen, Clostridium difficile. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically. The primary risk factor for CDI is antibiotic treatment, which disrupts the resident gut microbiota and leads to susceptibility to C. difficile. Interestingly, non-antibiotic associated CDI cases are on the rise, suggesting that unexplored host, environmental, and microbiota factors likely influence CDI. We are interested in identifying these environmental factors and defining underlying mechanisms of microbiota disruption and modulation of disease.
The research in our laboratory draws from numerous fields including microbiology, immunology, microbial ecology, host-pathogen interactions, and microbiota research. Our strategy is to leverage the strengths of high throughput sequencing technologies with more mechanistic strategies involving bacterial genetics, mass spectrometry, and imaging. Trainees in the laboratory gain interdisciplinary training and are involved in translational studies at the interface of basic and clinical research.
We are currently looking for highly motivated technicians, graduate students, and postdoctoral fellows. Available projects include:
The impact of environmental factors on the gut microbiota and C. difficile infection
There is growing evidence that environmental factors, such as diet, have a profound impact on the structure and function of the gut microbiota. With the rise of non-antibiotic associated CDI, we are interested in studying the potential impact of environmental factors on susceptibility to and severity of C. difficile. Of particular interest are non-steroidal anti-inflammatory drugs (NSAIDs), which are the most widely consumed pharmaceutical drugs world wide. Epidemiological data and our preliminary work suggest that NSAIDs may alter the gut microbiota and impact severity of CDI.
Pathogen-microbiota interactions during Clostridium difficile infection
Antibiotic treatment can have a profound impact on the structure and function of the gut microbiota, leading to a loss in colonization resistance to invading pathogens, such as C. difficile. However, the gut is not sterile following antibiotic treatment and pathogens like C. difficile are entering a polymicrobial environment upon colonization. Antibiotic resistant members of the microbiota, such as the Enterococci, frequently thrive following antibiotic treatment and can become highly abundant during CDI. We are interested in studying how members of the gut microbiota that remain after antibiotic treatment impact C. difficile during infection. Interspecies interactions can be attributed to the development of numerous polymicrobial infections and bacterial synergy is associated with disease exacerbation and increased antimicrobial resistance.
If you are interested in our work and would like to join the team, please reach out to Dr. Zackular directly.