1 Hospital Drive
Columbia, MO 65212
Understand the role of macrophage-specific Notch1 in the development and progression of abdominal aortic aneurysm (AAA). Notch1 signaling has recently gained substantial interest because of its potential participation in a diverse array of inflammatory diseases. AAA, defined as a localized dilation of the abdominal aorta, is a life-threatening disease, which has an estimated incidence of 2 to 4 percent in the adult population. AAA is characterized by activation of the inflammatory response causing extensive remodeling of the aortic wall. To understand the role of Notch1 in AAA, my laboratory has generated various knockout mice and has reported that loss of Notch1 interferes with the development of AAA at the initial stages by preventing the recruitment of macrophages. My short term-goal is to determine if pharmacologic inhibition of Notch signaling is a viable therapeutic strategy to modulate AAA. My long-term goal is to understand how Notch-1-dependent changes in macrophage functions affect other diseases such as atherosclerosis and cerebrovascular disease. I also have great interest in determining the molecular mechanism which defines the inverse relationship between diabetes and AAA.
Awards & Honors
- 1995: Gold medalist (MSc)
- 2007: Best poster award (Research Foundation Day), LSU Health New Orleans
- 2008: Best poster award (Research Foundation day), LSU Health New Orleans
- 2011: Young Investigator Award (Abdominal Aortic Aneurysm Epidemiology, Genetics, and Pathophysiology) in Pennsylvania
- 2011: Travel Award (American Heart Association, ATVB Council) in Orlando, Fla.
1. Notch1 in AAA: My most important contribution to the science in recent times relates to the roles of Notch1 signaling in AAA. AAA accounts for ~15,000 deaths annually and the average cost per discharge for a ruptured AAA is roughly estimated to be $50,000-90,000. Increased understanding of the mechanisms underlying the progression of AAA is required for the novel non-surgical cost-effective therapies to reduce AAA progression and rupture. My lab reported for the first time that an alteration in the dynamic balance of pro-inflammatory (M1) vs. anti-inflammatory (M2) macrophages correlates with the progression AAA. My publications also reported increased activation of Notch1 signaling in mouse and human AAA and its direct correlation with proinflammatory macrophages. In light of these data, my studies carry high contribution as I am studying Notch1 deficiency as a novel target to increase M2-differentiation of Mφ to create conditions optimal to halt AAA progression. My research has opened up new avenues for the therapeutic interventions for AAA progression and other labs have followed my research confirming the beneficial effects of Notch1 deficiency in AAA progression. My study was also highlighted in the “Recent Highlights of ATVB”. A patent has been filed for treating the patients with AAA by Notch inhibitors.
I. Cheng J, Koenig SN, Kuivaniemi HS, Garg V, Hans CP. Pharmacological inhibitor of notch signaling stabilizes the progression of small abdominal aortic aneurysm in a mouse model. Journal of the American Heart Association.3; 2014.