EXTRACELLULAR MATRIX IN VASCULAR DEVELOPMENT AND DISEASE
Project abstract
The goal of this training proposal is to develop the principal investigator, Dr. Chien-Jung Lin, into an independent
physician scientist. He has completed clinical training in Internal Medicine, Cardiology, Interventional Cardiology,
and postdoctoral fellowship at Washington University (WashU) before becoming Assistant Professor at Saint
Louis University (SLU). The career development plan described here will provide a formal course curriculum and
laboratory training in the study of cardiovascular biology, with a focus on neointimal formation. At the conclusion
of this award, Dr. Lin will have obtained the skills required to transition into an independent physician-scientist.
Dr. Ajay Jain, Professor of Pediatrics, will mentor Dr. Lin. An internationally recognized physician-scientist, Dr.
Jain successfully transitioned from a full-time clinician to a K08 awardee, and to recipient of NIH R01 awards
during his tenure at SLU. His experience will shepherd Dr. Lin at his current institution. Dr. Lin will continue to
benefit from connections with WashU, only 2 miles away, including co-mentor, Dr. Kory Lavine, who has
extensive experience in mentoring the career development of cardiologist-scientists. A local advisory committee
of leading clinician/scientists has been assembled to guide Dr. Lin’s scientific and career development. The
environment of SLU, combined with that at neighboring WashU available to Dr. Lin through SLU’s partnership
in Institute of Clinical and Translational Sciences, provides unparalleled resources, facilities, mentorship and
peer expertise for collaborations and career development. Dr. Lin will utilize the mentorship and the rich
resources available in this ideal training environment to define an important area of vascular biology.
Cardiovascular disease is the leading cause of morbidity and mortality in the industrial world. Despite advances
in stenting, some patients develop neointima within the stent, causing arterial occlusion. By comparing distinct
forms of neointima, it is apparent that the disruption or absence of intact internal elastic lamina (IEL) in a vessel
in the arterial milieu underlies neointimal formation. Due to the lack of animal models, it remains unclear how IEL
disruption leads to neointima. To address this issue, we recently developed a novel mouse genetic model of
neointima by smooth muscle-restricted deletion of elastin. Our findings suggest that neointima might be
associated with smooth muscle cell phenotypic changes and insulin-like growth factor (IGF) signaling.
The scientific objective of this proposal is to understand the fundamental cellular and molecular mechanisms
shared by various forms of neointima and explore the IGF/IGF binding protein pathway as a potential therapeutic
target. By completing the proposed aims, Dr. Lin will master the techniques for the analysis of single cell/nucleus
genomics and the study of neointimal formation. He will also gain important knowledge in genomics and
bioinformatics to complement his prior expertise in cancer biology and mouse genetics. With these skills and the
additional training outlined in the training plan, Dr. Lin will be well positioned to become an independent
interventional cardiologist-scientist at the forefront of the discovery for novel therapies for neointimal formation.