Marlies Meisel, PhD

In the Meisel Lab we are passionate to dissect the impact of how environmental factors such as the gut microbiota, physical exercise and diet/obesity impact on systemic immunity during health and complex diseases, such as cancer.

PROJECT: Gut-liver axis - Define the impact of the gut/liver microbiota in a novel mouse model of spontaneous liver disease/cancer

In 1907, the Russian scientist and Nobel laureate Ilya Ilyich Mechnikov (Elie Mechnikov) proposed that ‘many diseases which lead to chronic systemic inflammation, occurred as a result of increased gut bacterial translocation into peripheral organs’ [P., M. E. G. The Prolongation of Life: Optimistic Studies. Putnam's Sons (1907)]. Today, we still only know that gut bacterial translocation is associated with many diseases, such as cancer. Yet, there is a lack of cause-effect studies.

In one of our projects in our lab we are eager to define the mechanism how commensal gut microbial signals (gut and tissue) initiate liver disease/cancer in a novel mouse model of spontaneous liver disease.

Cutting edge in vivo (transgenic mice, gnotobiotic mice, fecal microbial transplants (mouse/humans)) and in vitro approaches are combined with single cell RNAseq as well as Next Gen metagenomic sequencing. In this project our lab collaborates with the Liver Research Center in Pittsburgh (http://www.livercenter.pitt.edu) and experts in microbial mediated liver disease in other US institutions to establish a strong translational axis.

The ultimate goal is to improve existing treatment options and establish novel therapeutic strategies to identify individuals at risk to develop primary liver disease/cancer.

PROJECT: Define the underlying mechanisms how physical exercise/obesity impacts on systemic tumor immunity and anti-cancer immunotherapy efficacy.

In recent years, epidemiological studies have linked obesity and physical activity with cancer incidence, progression and mortality. Obesity is an established risk factor for cancer progression while physical exercise has the potential to modify the tumor microenvironment and improve cancer outcomes. Here we will dissect the underlying mechanisms of how physical exercise/obesity impacts on systemic tumor immunity and anti-cancer immunotherapy efficacy with a focus on the gut and tumor microbiome.

We will use state of the art approaches such as, transgenic/gnotobiotic mice, fecal microbial transplants (mouse/humans)), motorized treadmill for mice, various tumor models, multi-color flow cytometry/sorting (Cytek Aurora), single cell RNAseq as well as Next Gen metagenomic sequencing.

Understanding the mechanistic effects of obesity and physical exercise on the tumor microenvironment can uncover new therapeutic targets and lifestyle changes that potentially change disease outcome.

PROJECT: Determine the role of spontaneous bacterial translocation on systemic immunity

The host is constantly communicating with microbes. The human body is not sterile and live bacteria can be detected in healthy individuals. What leads to gut bacterial translocation? And is there a specific “window of opportunity” where gut microbiota predominately translocates into extra-intestinal organs?

Germ free mice are much more susceptible to infections and have a substantially impaired myeloid immune system. Is there a requirement for bacterial translocation? Is this a symbiotic process which is beneficial to the host? Is this a required mechanism that trains the innate immune system to combat infections? Our lab will define which microbial (type/strain of commensal), environmental/metabolic (age, nutritional status, temperature) and genetic/epigenetic factors impact on spontaneous gut bacterial translocation and will evaluate its effects on development of the immune system during health and distress.

We will use a strong imaging approach, bacterial flow cytometry/sorting, genetic bacterial engineering and gnotobiotic mouse models combined with targeted fecal microbial transplants and metagenomic sequencing.