Dr. Ramon Klein Geltink is an Assistant Professor in the department of Pathology and Laboratory Medicine at UBC, an Investigator at the BC Children’s Hospital Research Institute and an investigator in the of the Edwin S.H. Leong Centre for Healthy Aging. He was recruited to UBC in 2019 after having trained at St. Jude Children’s Research Hospital in Memphis, TN, USA and the Max Planck Institute for Immunobiology and Epigenetics in Freiburg, Germany for his PhD and Postdoc respectively.
The Klein Geltink research team aims to better understand the role of metabolism in the regulation of immune cell function. We aim to expand our understanding of the role of metabolism in the dysfunction of immune cells in cancer, and to uncover therapeutic targets to improve cancer immunotherapy. When cells are confronted with changing environments they have to adapt to their new surroundings to maintain cellular function, including cancer cell cytolysis. This adaptation is especially relevant for immune cells that move throughout the body and encounter different levels of metabolites and nutrients in the blood, tissues or tumours they traverse. The availability of nutrients influences immune cell metabolism, but having a metabolite available does not mean a cell will necessarily use it. Cellular metabolism consists of an interconnected network that is influenced by at least 4 factors which we aim to better understand: 1. Metabolite / cellular nutrient availability How do immune cells sense changes in the context of their nutrient environment, and how are these signals transmitted? 2. Metabolite transport into the cell How are metabolite transporters regulated during immune cell activation and in the tumour microenvironment? 3. Metabolic enzyme and pathway activity Metabolic enzymes are often considered "household genes" for control experiments. But we are aiming to better understand how the activity of these enzymes is modulated. 4. Availability of enzyme cofactors Most, if not all, metabolic enzymes are dependent on substrate and cofactors. We are interested in the sensing of cofactor status and their effects on metabolic pathway activity and immune cell function. Not all immune cells use the same metabolic pathways even if metabolites are abundant, transporters and enzymes are expressed, and cofactors are available. The cell-specific response can be regulated by growth factors, cytokines, or immune cell receptor signaling, and we aim to better understand the signals that provide the instructions for metabolic pathway use within the setting of immune homeostasis and during an anti-tumour response.