Our laboratory is working to understand how cancer impacts the global metabolic balance of the organism. We are defining how a localized tumor disrupts normal nutrient partitioning and the effects of this interaction on physiology, behavior, and adaptation. By considering cancer in the context of its macroenvironment, we hope to translate our insights into new approaches to early detection, risk stratification, and treatment of lethal malignancies.
Cancer is made up of aberrantly proliferating cells, which fail to respond appropriately to the normal regulatory mechanisms that impede growth. To grow tumors must acquire an adequate supply of building blocks to manufacture the macromolecules needed for cell growth and division. Research focused on how cancer cells repurpose cellular metabolism to promote proliferation has revealed incredible plasticity, allowing cancer cells to remain anabolic in a broad range of nutrient contexts. Universally, tumors must usurp the nutritional resources from the body and repurpose them for tumor cell growth. In its most advanced stages, this is evidenced by the wasting syndrome, cachexia, which is characterized by muscle and organ wasting, weight loss, and depleted physiologic reserve. Nutritional supplementation is ineffective in reversing cachexia, implying that cancer enacts a devastating metabolic program. Defining this process in early stages of tumor development, when cachexia could be prevented or reversed, has remained an elusive task. Despite recognition as a fundamental component of tumor growth, how cancer redirects metabolic resources from the host, and the impacts of this process on tumor growth, symptoms, and patient resilience remain poorly understood. We aim to define the biobehavioral signature of early cancer development and metabolic reprogramming and to identify the key pathways underlying this phenomenon.
Our laboratory focuses primarily on pancreatic cancer, among the deadliest and most metabolically disruptive tumors. Pancreatic ductal adenocarcinoma (PDAC) is currently the 4th leading cause of cancer death, with fewer than 10% of PDAC patients alive 5 years after diagnosis. Physicians are seldom alerted to a problem in the pancreas until advanced tumors have developed, so most patients present at an unresectable, and thus incurable, stage of disease. Although the majority of cases are sporadic, there are currently no effective screening strategies for the population. PDAC is often preceded by adult onset diabetes and is commonly associated with cachexia at diagnosis, implicating early metabolic reprogramming as a defining feature. Decreased total daily activity is among the first observed signs of sickness in humans
and preclinical animal models of acute and chronic diseases. Asthenia, the symptomatic surrogate for decreased activity, is the most common presenting symptom of PDAC, reported by nearly 90% of patients with localized disease. We believe that this reflects a sensitive behavioral measure of metabolic reprogramming. We utilize orthotopic and genetic mouse models of PDAC to identify early behavioral and physiologic signatures of cancer development. We are also evaluating mHealth approaches to identifying patterns associated with cancer development in high risk PDAC populations. Working with our colleagues in the Cancer Early Detection Advanced Research Center and Brenden Colson Center for Pancreatic Care to we aim to define the molecular and biochemical fingerprint of early PDAC in both mouse models and clinical samples.
Our current interest is in identifying novel physiometric approaches to PDAC screening. We are also interested in how cancer growth effects whole body metabolism and the role this plays in physiologic reserve and adaptation to metabolic challenges. Through this work, we hope to advance understanding of tumor-host crosstalk and its relationship to tumor growth, patient resiliency, and quality of life.