The research of Yan Bi, M.D., Ph.D., focuses on pancreas physiology, pancreatitis and pancreatic cancer. Her research contributions can be divided into four key areas:
- Signaling pathways in the regulation of pancreatic acinar secretion
- Tumor microenvironment in pancreatic cancer progression
- Anticoagulation in acute pancreatitis therapy
- Early pancreatic cancer detection
- Signaling pathways in pancreatic acinar secretion. Dr. Bi demonstrated that cholecystokinin (CCK) receptors were coupled with not only Gq but also G12 and G13 trimeric G proteins, as well as Rho, Rac and cdc42 small G proteins. These signaling pathways regulate pancreatic acinar cell cytoskeletal rearrangement and physiological and pathological digestive enzyme secretion and activation. These novel findings not only shed new insights on the mechanisms of pancreatic acinar cell secretion but also revealed potential therapeutic targets for pancreatitis therapy.
- Anticoagulation and treatment of acute pancreatitis. Dr. Bi and her team have generated a novel transgenic mouse model for human hereditary pancreatitis by expressing human PRSS1-R122H. The transgenic mice recapitulated the clinical course of the human disease, which is the first successful animal model for hereditary pancreatitis. They discovered that anticoagulation was able to improve the severity of pancreatitis. Together with a retrospective patient study, these investigations showed that patients who were on anticoagulation medication have a better clinical outcome compared to those who were not; this suggests coagulopathy is critical in the initiation and prognosis of acute pancreatitis.
- Tumor microenvironment in cancer progression. Dr. Bi explored the complexity of the tumor microenvironment. She dissected the pathways showing how stellate cells sense and respond to the surrounding environment by macrocytosis of matrix, and how sphingosine-1-phosphate (S1P) is reciprocally used by both stellate cells and cancer cells in tumor growth. These studies have provided potential targets for pancreatic cancer treatment.
- Early pancreatic cancer detection. Dr. Bi is collaborating with the PRECEDE consortium, which aims to improve early pancreatic cancer detection using artificial intelligence and digital wearable devices for at-risk patients to assist in pancreatic cancer screening and surveillance.
Significance to patient care
Pancreatic cancer has a five-year survival rate of less than 10%. Only 20% of patients are diagnosed at an early disease stage; most are diagnosed in advanced stages. Early-stage pancreatic cancer bears significant survival benefit (40%) compared to advanced stages (less than 5%). Therefore, early diagnosis is crucial to improve pancreatic cancer prognosis and decrease mortality. However, there is no proven strategy to diagnose pancreatic cancer early. Dr. Bi's research effort to enrich strategies for patients at high risk for pancreatic cancer aims to provide continuous, affordable, noninvasive and patient-centered care that can screen patients for early pancreatic cancer detection, thereby improving pancreatic cancer survival.
The new transgenic mouse model that replicates human-hereditary pancreatitis by expressing human PRSS1-R122H found that coagulopathy is critical in the initiation and prognosis of acute pancreatitis. This discovery has led to a clinical trial that may provide effective treatment for acute pancreatitis, a common disease lacking targeting therapies.