In the last decade therapeutic strategies have evolved to utilize living cells as a means to treat human disease. These therapies include the engineering of immune cells, stem cells and bacteria to selectively target mechanisms that underlie cancer, immune and metabolic diseases. The Cohen Laboratory focuses on the development of these novel therapies and their application to human diseases.
The human microbiome is believed to be important to normal physiology but we have limited knowledge of how commensal bacteria dictate, for example, immunity and metabolism (i.e. effector functions). The most common method for studying human microbiota has involved the sequencing of bacterial DNA in patient cohorts. Sequence-based studies are likely to provide a short-term solution to expand our understanding of the small number of known signaling systems, however, I believe that unbiased functional discovery methods are more useful to identify the still largely unknown host-microbial interactions that contribute to human health. The focus of my laboratory is the study of host-microbial interactions by 1) developing methods for the systematic identification of human microbial effector functions and 2) determining the role of bacterial effectors in the pathogenesis of human diseases. This research platform represents a shift from “sequence first” studies of the microbiome to “function first” studies that are more easily translated into etiologic and therapeutic studies of commensal bacteria and human disease. As each effector function is isolated in vitro it is studied in vivo in mouse disease models as a generalizable strategy to develop microbial therapies. These microbial therapies or live biotherapeutics represent an entirely new therapeutic paradigm and their development is a primary focus of the Cohen Laboratory.
Stem cell therapies
Crohns disease is an immune disease of the gastrointestinal tract that affects over 1 million people in the United States alone. It is believed to be a disease of host-microbial interaction whereby mechanisms that govern tolerate to commensal organisms break down and lead to unrestrained immune activation. Therapies that target this aberrant immune response are the basis for treatment but for many patients these therapies fail leaving them with significant disability and increased mortality. For these patients stem cell transplantation offers a chance at a meaningful therapeutic outcome though the mechanisms that underlie this therapy are almost entirely unknown. Using advanced molecular phenotyping methodologies including mass cytometry and single cell sequencing the Cohen Laboratory aims to understand the mechanisms of stem cell transplantation for Crohn’s disease as part of an ongoing clinical trial (https://clinicaltrials.gov/ct2/show/NCT03219359). This trial is the first of its kind in the use of immunosuppression post transplantation as a strategy to maintain long-term disease-free remission. The Cohen Laboratory is also exploring new strategies to further enhance the efficacy of stem cell transplantation by targeting immune pathophysiology in hematopoietic stem cells.