Aida Habtezion, MD, MSc, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine
Research Description: Chronic pancreatitis is the most common cause of pancreatogenic (type 3c) diabetes (T3cDM), a form of secondary diabetes caused by destruction and pathologic processes involving the exocrine pancreas. This entity remains poorly understood and patients are frequently misdiagnosed. It is complex with increased peripheral insulin sensitivity and decreased hepatic insulin sensitivity creating a form of “brittle’ diabetes that is hard to manage. Recent studies and hypotheses suggest important immune related mechanisms at the core of this disease pathogenesis. These pathways also appear to be important to diabetes associated with pancreatic cancer. One of Dr. Habtezion’s major research focuses includes understanding immune mechanisms and identification of potential immune-based therapeutic targets in pancreatitis. Over the past years her lab has elucidated a protective role for heme-oxygenase 1 (HO-1) expressing macrophages in pancreatitis. Furthermore, the lab showed a therapeutic role for HO-1 down-stream effectors (biliverdin and carbon monoxide; CO). Notably, the lab demonstrated a cellular therapy based on adoptive transfer of CO-primed monocytes in pancreatitis. More recently her research has expanded to chronic pancreatitis and identified immune mechanisms in fibrosis progression. This work provided key preliminary data to a recently-funded NIDDK/NCI UO1 consortium grant to study chronic pancreatitis and its associated complications such as diabetes with Drs. Park and S.K. Kim, SDRC investigators. Moreover, her group recently identified an immunologic basis to explain how smoking promotes progression of chronic pancreatitis.
Selected relevant publication (Stanford DRC members in BOLD):
1. Xue J and Habtezion A. Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition. J Clin Invest 124:437-47, 2014.
2. Kambhampati S, Park W, Habtezion A. Pharmacologic therapy for acute pancreatitis. World J Gastroenterol. 20: 16868-80, 2014.
3. Xue J, Sharma V, Hsieh MH, Chawla A, Murali R, Pandol SJ, Habtezion A. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nature Communications 6:1-11, 2015.
4. Edderkaoui M, Xu S, Chheda C, Morvaridi S, Hu RW, Grippo PH, Mascarinas E, Principe DR, Knudsen B, Xue J, Habtezion A, Uyeminami D, Pinkerton KE, Pandol SJ. HDAC3 mediates smoking-induced pancreatic cancer. Oncotarget 7:7747-60, 2016.
5. Bronsart L, Nguyen L, Habtezion A, Contag C. Reactive Oxygen Species Imaging in a Mouse Model of Inflammatory Bowel Disease. Mol Imaging Biol.18:473-8, 2016.
6. Xue J, Zhao Q, Sharma V, Nguyen LP, Lee YN, Pham KL, Edderkaoui M, Pandol SJ, Park W, Habtezion A. 2016. AhR ligands in cigarette smoke mediate immune activation and promote fibrosis in chronic pancreatitis. Gastroenterology 151(6):1206-1217.