Yongho Bae, PhD, in a lab setting.

Yongho Bae, PhD, was accepted into the Empire Discovery Institute’s LeapRx program to study vascular and cardiac stiffening associated with cardiovascular disease.

Bae Receives Funding to Develop Drug for CVD

Published December 15, 2022

By Dirk Hoffman

Yongho Bae, PhD, assistant professor of pathology and anatomical sciences, has received a $250,000 sponsored research award from the Empire Discovery Institute (EDI) to investigate the role a novel mechanotherapeutic target, discovered in his lab, may have on vascular and cardiac stiffening commonly associated with cardiovascular disease (CVD). 

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CVD is the leading cause of death in the United States and globally. According to estimates from the Centers for Disease Control and Prevention, CVD caused the deaths of approximately 17.9 million people worldwide (in 2019) and 697,000 Americans (in 2020). The annual cost of national health care for CVD in the United States is more than $200 billion.

Reducing Arterial Stiffening Process

Arterial and cardiac stiffness, defined as mechanical/physical force generated on the blood vessel and myocardium, are key risk factors for a wide range of CVD.

Vascular smooth muscle cells (VSMCs) and cardiac fibroblasts (CFs) play an indispensable role in vascular repair after arterial or cardiac injury.

However, pathologies arise when VSMCs continue to proliferate long after the neovascularization and vascular remodeling phase ends. This contributes to intimal vascular thickening (neointima formation) associated with arterial stiffening.

Similarly, CFs are activated at sites of injury in the myocardium where they differentiate into myofibroblasts (the primary pathological fibroblast phenotype) and secrete excessive amounts of collagen-rich extracellular matrix (ECM). This ECM remodeling induces a fibrotic microenvironment that induces cardiac fibrosis, and ultimately heart failure. Bae’s team asserts that controlling aberrant VSMC and CF behaviors may help reduce or prevent cardiovascular events.

The goal of this sponsored project will be to develop a treatment that either reduces or prevents arterial stiffening and the associated pathological changes to VSMC and CF that lead to cardiovascular events in patients. Treatments specifically targeting the molecular-mechano pathways linked to arterial stiffness are not yet available. 

This project will involve synthesizing, testing and optimizing compounds that could inhibit the novel mechanotherapeutic target that Bae, and his MD/PhD student, Joseph Brazzo, have identified.

Empire Discovery Institute and LeapRx

EDI is an integrated drug discovery and development accelerator located in upstate New York, and formed as an equal partnership between the University at Buffalo, University of Rochester and Roswell Park Comprehensive Cancer Center.  

The organization represents a nimble and transformative approach to the creation of new medicines by working at the interface between basic academic research, fundamental discoveries and the pharmaceutical industry. EDI serves an important role to the academic research community by bridging the “valley of death” which divides academic innovation from commercial translation.  

To advance his research, Bae was accepted into EDI’s LeapRx program, a collaborative multi-year research initiative, in partnership with the Novo Nordisk Bio Innovation Hub, that co-invests, incubates and accelerates novel drug discovery programs in cardio-metabolic diseases and rare blood disorders. Projects accepted into LeapRx, receive funding and guidance from pharmaceutical industry experts to help advance scientific discoveries into important new medicines for commercialization. 

LeapRx projects initially receive $250,000 in total program support and up to $10 million in total program support over five years, subject to annual EDI review. Bae is one of the first two investigators to receive funding as part of the LeapRx program. 

“EDI is very excited to be supporting Dr. Bae’s program as part of LeapRx and looks forward to generating additional data in the coming year that will advance this program closer to clinical study” says Ron Newbold, Empire Discovery Institute’s interim CEO.  

“This approach to mitigating the underlying process of arterial stiffening could prove a major advance in addressing cardiovascular disease, very early in the disease process, and improve the course of treatment for this major risk factor in heart disease globally,” he says. “We look forward to contributing to validation of this hypothesis and moving this ahead as quickly as possible.”