Inflammation has been speculated to play a role in cancer initiation and progression from the early days of cell biology. My research focused on identifying novel molecular mechanisms by which the inflammatory tumor microenvironment contributes to tumor growth and how cancer-associated inflammation could be used clinically to improve patient outcome.
Ferritin in Breast Cancer:
Ferritin is a 450 kilodalton protein complex. Its primary function is to store iron in a non-toxic and bio-available form. Ferritin has long been noted to have higher levels in tumor tissues. This increase has led some to postulate a link between iron and cancer. We demonstrated that ferritin is primarily localized within the tumor stroma specifically in tumor-associated macrophages. Ferritin was also detected in acellular regions suggesting active secretion. Subsequent In vitro experiments identified a novel role for extracellular ferritin in stimulating growth of cancer cells independently of iron content. [Image: a ferritin-rich macrophage infiltrating an invasive ductal carcinoma of the breast.]
Inflammation in Cancer
Ferritin; CD68; DNA
The Problem of Irroproducibility
The concept of scientific automation began with the birth of the scientific method itself. When Francis Bacon proposed a stepwise process through which any knowledgeable person can practice science, he hinted that science is innately algorithmic. These scientific algorithms have been hard to identify and replicate due to the fact that they occupy three independent yet connected domains: technical experimentation, knowledge management /integration, and hypothesis generation.
The problem of irreproducibility (the inability to independently replicate some scientific findings) threatens to undermine public and governmental trust in the scientific enterprise. The cause of this problem is often misconceived as intentional fraud. Unfortunately, most of it occurs though a matrix of statistical, technical, and psychological biases which are highly influenced by external factors. I am curretnly exploring the psychological biases that may underlie this crisis. I am also working on the development of objective quality metrics in the scientific literature in order to align academic motives with quality.
Automation of Scientific Discovery
Inflammation and Therapy Response:
Herceptin is a monoclonal antibody targeting the HER2 membrane protein which is overexpressed in approximately 25% of breast cancer patients. It was the first approved targeted biological therapy for cancer and has led to remarkable improvement in prognosis. However, almost half of the patients do not respond to Herceptin. We examined the utility of inflammatory markers to stratify patients response. Elevation in inflammatory biomarkers (ferritin and CRP) identified a subset of patients (~25%) that were non-responsive to Herceptin containing therapy.