Barrett's Esophagus Study
This study includes the impact of Obesigenic Diets on the development of Barrett’s Esophagus (BE) and Esophageal Adenocarcinoma (EAC) in the L2-IL-1β Transgenic mouse, as well as projects on chemoprevention of BE and EAC. Studies are also in progress to develop Transgenic and Knock Out mouse models of candidate genes for BE and EAC determined in human pedigree studies.
Colon Cancer Studies
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. New approaches are needed to elucidate the biology of this disease, to identify individuals at high risk for this disease, and to develop new and better-targeted strategies for preventing this disease. 15-PGDH is a novel colon cancer tumor suppressor that provides new opportunities to address these challenges.
Blood Malignancy Studies
Hematologic malignancies account for around 10% of new malignancy cases each year, with leukemia being the most common disease type incident in childhood. Acute promyelocytic leukemia (APL), a leukemia subtype, has recently been shown to have a strong correlation with increased BMI, which has been associated with an increased risk of disease differentiation and relapse in patients. By utilizing new techniques to better understand the disease’s biology, improved identifiers for individuals at risk for malignancy pathogenesis as well as enhanced targeted strategies for disease prevention could be developed. PML-RARα is a novel oncogene that provides new opportunities to address these challenges and accurately recapitulate the APL phenotype.
Multiple myeloma (MM) is a disease resulting from malignant plasma cell proliferation, typically characterized by anemia, lytic bone lesions, hypercalcemia, and renal failure. Myeloma is preceded by an asymptomatic precursor state known as Monoclonal Gammopathy of Unknown Significance (MGUS), a condition denoted by the overproduction of monoclonal immunoglobulin antibodies (M-protein). Prior studies have found that obesity plays a role in not only the incidence of MGUS, but also the corresponding transition to MM. Obesity-linked cancers such as MM have been associated with increased levels of proinflammatory cytokines, e.g., interleukin 6 (IL-6), which promote cancer development by driving malignant cell growth. IL-6 has been purported to act as both a growth and survival factor in myeloma progression, presenting a potential target for disease prevention. Using a transgenic murine model, we will determine whether increased levels of circulating IL-6 are temporally associated with an early, obesity-associated conversion of MGUS to MM.