Research
Cancer, at a cellular and organismal level, is at least in part a metabolic disease. Cancer cells have altered metabolism and rely on increased glucose consumption to accommodate nutrient demand and proliferation. Systemically, cancer can induce profound changes in nutrient intake and handling that culminate in cachexia. Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD).
In IL-6-associated murine models of cancer cachexia where hepatic ketogenesis is suppressed, KD delays tumor growth but accelerates cachexia onset and shortens survival. Mechanistically, this uncoupling is a consequence of the biochemical interaction of two NADPH-dependent pathways. Within the tumor, increased lipid peroxidation and, saturation of the GSH system lead to ferroptotic death of cancer cells. Systemically, redox imbalance and NADPH depletion impair corticosterone biosynthesis. Administration of dexamethasone, a potent glucocorticoid, increases food intake, normalizes glucose levels, delays cachexia onset, and extends the survival of tumor-bearing mice fed KD while preserving reduced tumor growth.
Our study emphasizes the need to investigate the effects of systemic interventions on both the tumor and the host to accurately assess therapeutic potential.
Cancer - a disease of the whole body
Patients with cancer display tumor-driven physiological, biochemical, and immunological alterations. In a number of laboratory and clinical research projects, we investigate how cancer interacts with the organism. Sustained inflammation reprograms the body in the context of cancer progression and cancer associated cachexia, a wasting condition that severely reduces quality of life and therapeutic options.
COVID-19 - a disease of the whole body
Substantial similarities between the pathways and organismal response pattern in COVID-19 and cancer exist. Therefore, we were able to pivot our work to contribute to treatment research for COVID-19. Sustained increased inflammation and immune activation (cytokine release syndrome) drive poor outcome for patients with COVID-19. Modulating the host response during COVID-19 may offer benefit to the patients.
Statistical modelling of host organ function
Developing and utilizing the best approach to data collection and analysis is essential for laboratory and clinical research. Using large data sets from clinical trials and routine clinical practice, we have contributed to development of care for patients. We have developed a new model to estimate glomerular filtration rate (GFR).
