Cachexia, or disease-associated wasting, is a common occurrence in cancer, renal failure, heart failure and other chronic diseases. This devastating state of malnutrition is brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. This syndrome is also frequently accompanied by other systemic symptoms, including debilitating fatigue, enhanced pain sensation, and difficulties with learning and memory. The severity of cachexia in many illnesses is the primary determining factor in both quality of life, and in eventual mortality. There is currently no effective pharmaceutical treatment, and this disorder of energy homeostasis is poorly understood. Research in Dr. Marks' lab has led to the hypothesis that an increase in melanocortin signaling in the hypothalamus may be responsible for many of the features of illness-induced cachexia and failure to thrive. The lab has demonstrated that the growth failure and loss of lean body mass that would otherwise accompany acute and chronic disease could be reversed by pharmacological blockade of melanocortin signaling, and by genetic deletion of the type 4 melanocortin receptor (MC4-R).
Recently, the lab is focusing on the mechanisms whereby peripheral inflammation and chronic disease leads to inflammation within the brain. We have demonstrated that the immune system in the brain is distinct from that found in the periphery, and its activation leads to complex changes in brain function. Collectively, the data generated in this lab suggests a model wherein brain immune activation leads to disruption of normal regulation of appetite, metabolism, arousal, and memory. The lab is actively collaborating with industrial partners to develop novel treatments for these debilitating symptoms, both to improve quality of life, and to enhance survival from acute and chronic disease challenges.
Childhood growth and weight regulation
Dr. Marks has an active clinical and basic science research program related to the problem of childhood obesity and type 2 diabetes. Dr. Marks also serves as the Senior Associate Dean for Research in the School of Medicine, Associate Director of the OHSU M.D. Ph.D. Program, and as the Director of the Papé Family Pediatric Research Institute at OHSU.