Zhihua Jiang, MD, PhD : Research

My research projects aim to understand mechanisms that drive initiation and progression of aortic aneurysms and dissections (AADs) and to identify critical cellular and molecular targets that hold promise for further translation to effective therapeutics.

1] Danger signals. Danger signals, particularly those triggered by damage associated molecular patterns (DAMPs), are double-edged swords that may facilitate or impair tissue-repairing processes. To this end, my laboratory focuses specifically on TLR-7 signaling incited by self-RNAs released from stressed or dying cells. Multiple mouse models and human tissue samples are employed to address the context-dependent effects of TLR-7 signaling in the development of AADs.

2] Dysregulated adaptive immune responses. Mounting evidence suggests that the biological outcome of immune injury to an organ depends on local immune cell differentiation. It has been postulated that type 2 immunity, a response primarily driven by Th2, NKT2, and ILC2 cells, may drive structural degeneration in target organs, such as the aorta. In contrast, type 1 immunity may direct cells to undergo hyperplastic responses. Since adaptive immunity is activated in human AADs, our lab is investigating the role of type 2 immunity in AAD development.

3] Impact of cytoskeleton deficiency on cell-signaling. Smooth muscle cells sense changes in the mechano-environment via their cytoskeleton system. They transduce mechano-stress into biochemical signals in order to maintain their mechano-homeostasis. Dysfunction of the cytoskeleton system has been implicated in the development of AADs. Currently, we are investigating risk factors, such as smoking and male gender, that render the aortic wall vulnerable to structural weakening and degeneration via impaired the cytoskeleton dynamics and signaling.