Marcel van den Brink Lab
Research Lab Overview
The van den Brink lab focuses on understanding the intestinal microbiome as an immune modulator, the role of thymic regeneration in immune response and clinical outcomes, and the mechanisms of chimeric antigen receptor (CAR) T cells in hematologic malignancies. These studies inform the development of clinical trials testing therapeutic strategies to enhance the efficacy and decrease the toxicity of cancer immunotherapies.
The gut microbiota consists of a community of diverse microbes and has many effects on human (patho)physiology. We have demonstrated that microbiota composition undergoes significant and frequent changes during allogeneic hematopoietic cell transplantation (allo-HCT) and have identified patterns of microbiome disruption that are associated with clinical outcomes. For example, patients with high microbial diversity, relative abundance butyrate producers, and dietary fiber intake have a significantly increased overall survival. Hence, we are investigating dietary interventions and live biotherapeutic products to alter microbiome composition and improve the outcomes of cancer therapies.
We are also studying thymic regeneration, which is critical for the renewal of immune competence following thymic injury. Unfortunately, the thymus is highly sensitive to acute injury from cytoreductive conditioning, as well as to aging-related thymic involution. We have demonstrated that we can harness pathways of thymic regeneration to promote immune reconstitution and improve outcomes, especially following allo-HCT. We aim to develop strategies for thymic regeneration to address thymic involution and immune system decline, with a focus on therapeutic interventions for patients undergoing cancer therapies.
Finally, we are investigating methods to overcome mechanisms of resistance to CAR T cell therapies, which are a newer therapeutic option for patients with hematologic malignancies. While CAR T cell therapies are curative in some recipients, improving their efficacy and abating toxicities are unmet needs in oncology. We are developing novel CARs and CAR platforms targeting human antigens associated with hematologic malignancies for human therapeutics.
Marcel van den Brink, M.D., Ph.D., is President of City of Hope Los Angeles and National Medical Center, Chief Physician Executive, and a Member of the Hematologic Malignancies (HM) Program. The van den Brink laboratory studies, through perpetual dialogue between investigation in mice and humans, three areas related to bone marrow transplantation and immuno-oncology: the intestinal microbiome as an immune modulator, thymic regeneration, and chimeric antigen receptor (CAR) T cells.
