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 understanding and developing these novel therapies for the application to human diseases especially inflammatory bowel disease (IBD). IBD is believed to be a disease of host-microbial interaction whereby mechanisms that govern tolerance 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. The Cohen Laboratory is specifically interested in why patients with IBD develop resistance to standard therapies and how cellular, regenerative and live biotherapeutic therapies may circumvent therapeutic resistance and promote true intestinal healing in IBD.

Cellular and regenerative therapies
Standard therapies for the treatment of IBD commonly target an aberrant inflammatory response but for a large number of patients these therapies are insufficient. The Cohen Laboratory is interested in understanding why patients with IBD develop medically refractory disease and exploring how cellular or regenerative therapies may circumvent medically refractory pathophysiology. As part of this clinical/translational research program, Dr. Cohen is the director of the Crohn’s Disease Stem Cell Transplant Program . This program is the first of its kind in the United States bridging multiple clinical and basic science departments to navigate patients with severe medically refractory Crohn’s disease through stem cell transplantation while employing cutting edge translational methods to understand why patients develop refractory Crohn’s disease and the therapeutic mechanisms of stem cell transplantation. Using advanced molecular phenotyping methodologies (mass cytometry, single cell sequencing) and functional interrogation of hematopoietic stem cells (xenograft models, in vitro differentiation), the Cohen Laboratory has begun to understand how cellular and regenerative therapies may reshape the Crohn’s disease treatment landscape and explore novel Crohn’s disease pathophysiology that involves the impairment of hematopoietic stem cells and regenerative cellular pathways.

Live biotherapeutics
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, unbiased functional discovery methods are more useful to identify the still largely unknown host-microbial interactions that contribute to human health. The Cohen laboratory studies host-microbial interactions with the aim 1) to determine how bacteria shape mucosal immune and epithelial responses and 2) to develop these interactions into novel live biotherapeutics using genetically modified organisms. The Cohen laboratory has multiple active areas of investigation into how human microbiota shape myeloid differentiation and can be utilized therapeutically to promote epithelial regeneration.