Zhiyong Lin, PhD
 |
(he/him) |
Associate Professor, Division of Cardiology, Department of Medicine, School of Medicine
Graduate Programs
- Full Member - Molecular and Systems Pharmacology
Education
Postdoctoral Fellow, Brigham and Women’s Hospital, Harvard Medical School, 2006PhD, Eastern Virginia Medical School, Old Dominion University, 2002
Contact Information
Email: zhiyong.lin@emory.edu
Phone: 404-712-0974
Address:
Health Sciences Research Building II, Room N240
1750 Haygood Drive
Atlanta, GA 30322
The broad scope of my research program seeks to understand the fundamentals of cardiovascular function. Specifically, I am interested in the molecular mechanisms that govern vascular homeostasis and how the breakdown of these mechanisms significantly contributes to the onset and progression of many vascular pathologies. My lab uses a variety of techniques, including, cellular and molecular biology, biochemistry, and mouse models to study vascular diseases, including atherosclerosis, aortic aneurysm, thrombosis and peripheral artery disease, with the ultimate goal geared toward the development of strategies for disease prevention and treatment.
Regulation of important cardiovascular signaling pathways has become an active pursuit of pharmacological intervention for disease treatment. However, nodal determinants that regulate signaling changes in the cardiovasculature are not well understood. Toward that end, our ongoing research efforts have been focused on the signaling events that control vascular inflammation and remodeling. Current efforts in the lab center on dissecting the regulatory roles of two important signaling regulators: Cellular Communication Network (CCN) factor proteins and Protein phosphatase 2A (PP2A) in cardiovascular function.
CCN proteins are secreted matricellular proteins that interact with growth factors, the extracellular matrix (ECM), cell surface integrins and other receptors to promote ECM-intracellular signaling. Our published and unpublished work has led to the appreciation that CCN3 serves as an important regulator of vascular health. We found that that CCN3 mitigates the formation and progression of aortic aneurysm (AA) in both thoracic and abdominal regions of aorta. Our recent data points toward CCN3 deficiency as a major contributor to 1) endothelial dysfunction and 2) the loss of barrier integrity, both instrumental in driving the pathology of thoracic aortic aneurysm. We have also shown that bone marrow-derived CCN3 is atheroprotective. Our ongoing work also substantiates the importance of CCN3 in the promotion of angiogenesis and vascular blood flow recovery after hind limb ischemia (HLI) induction. Mechanistic studies suggest that impaired HIF1a signaling and diminished VEGF-induced angiogenesis likely contribute to the loss of functional collateral blood flow in the context of CCN3 deficiency-induced ischemic injury.
Despite significant progress, there still remains significant unanswered questions, namely – what is the precise physiological role of CCN from different cellular origins in vivo? And what are the fundamental mechanisms responsible for CCN's action? Answers to these important questions will help fill in our knowledge gap of CCN and potentially guide therapy development.
Another area of interest for my lab is the role of protein phosphatase 2A (PP2A) in cardiovascular biology. PP2A is a potent de-phosphorylating enzyme within mammalian cells. It is a critical serine/threonine phosphatase that has been implicated in the regulation of many signaling pathways. Nascent observations from my laboratory revealed a profound loss of PP2A activity in murine models of heart failure, atherosclerosis and aortic aneurysms. This is supported by studies that show PP2A activation by the orally bioavailable small molecule activators of PP2A (SMAPs) markedly suppresses multiple pathologic conditions, including 1) cardiac remodeling in a murine model of heart failure, 2) plaque formation in atherosclerosis models and 3) aortic aneurysm progression. Building on these exciting findings, our overarching goal is to leverage both pharmacologic and genetic approaches to dissect the molecular basis and functional consequences of PP2A activation/inactivation in the above referenced disease settings.
Regulation of important cardiovascular signaling pathways has become an active pursuit of pharmacological intervention for disease treatment. However, nodal determinants that regulate signaling changes in the cardiovasculature are not well understood. Toward that end, our ongoing research efforts have been focused on the signaling events that control vascular inflammation and remodeling. Current efforts in the lab center on dissecting the regulatory roles of two important signaling regulators: Cellular Communication Network (CCN) factor proteins and Protein phosphatase 2A (PP2A) in cardiovascular function.
CCN proteins are secreted matricellular proteins that interact with growth factors, the extracellular matrix (ECM), cell surface integrins and other receptors to promote ECM-intracellular signaling. Our published and unpublished work has led to the appreciation that CCN3 serves as an important regulator of vascular health. We found that that CCN3 mitigates the formation and progression of aortic aneurysm (AA) in both thoracic and abdominal regions of aorta. Our recent data points toward CCN3 deficiency as a major contributor to 1) endothelial dysfunction and 2) the loss of barrier integrity, both instrumental in driving the pathology of thoracic aortic aneurysm. We have also shown that bone marrow-derived CCN3 is atheroprotective. Our ongoing work also substantiates the importance of CCN3 in the promotion of angiogenesis and vascular blood flow recovery after hind limb ischemia (HLI) induction. Mechanistic studies suggest that impaired HIF1a signaling and diminished VEGF-induced angiogenesis likely contribute to the loss of functional collateral blood flow in the context of CCN3 deficiency-induced ischemic injury.
Despite significant progress, there still remains significant unanswered questions, namely – what is the precise physiological role of CCN from different cellular origins in vivo? And what are the fundamental mechanisms responsible for CCN's action? Answers to these important questions will help fill in our knowledge gap of CCN and potentially guide therapy development.
Another area of interest for my lab is the role of protein phosphatase 2A (PP2A) in cardiovascular biology. PP2A is a potent de-phosphorylating enzyme within mammalian cells. It is a critical serine/threonine phosphatase that has been implicated in the regulation of many signaling pathways. Nascent observations from my laboratory revealed a profound loss of PP2A activity in murine models of heart failure, atherosclerosis and aortic aneurysms. This is supported by studies that show PP2A activation by the orally bioavailable small molecule activators of PP2A (SMAPs) markedly suppresses multiple pathologic conditions, including 1) cardiac remodeling in a murine model of heart failure, 2) plaque formation in atherosclerosis models and 3) aortic aneurysm progression. Building on these exciting findings, our overarching goal is to leverage both pharmacologic and genetic approaches to dissect the molecular basis and functional consequences of PP2A activation/inactivation in the above referenced disease settings.
Matricellular protein CCN3 in vascular homeostasis
Funding Agency: NIH
Project Dates: 07/15/2022 to 06/30/2026
Established Investigator Award/Regulation of smooth muscle cell plasticity in atherosclerosis
Funding Agency: American Heart Association
Project Dates: 04/01/2024 to 03/31/2029
Atlanta Society of Mentors (ASOM), 2023
Diversity: Inclusion in the Modern Workplace, 2022
Claire Holden (she/her)
Molecular and Systems Pharmacology
Entrance Year: 2020
