Fibrosis has been implicated in as much as 40 percent of all deaths worldwide. Over the last decade, researchers have made headway identifying the basic mechanisms of fibrotic disease, but there is much to be learned, and the imperative for rapid discovery remains pressing.
To jumpstart progress, UVA faculty have formed the Fibrosis Initiative. The goal of this grassroots project — supported at the highest levels of the University — is to mobilize the critical mass of UVA researchers conducting fibrosis-related studies and to build connections among them that will lead to potentially groundbreaking, cross-disciplinary investigations. The Fibrosis Initiative will facilitate multi-investigator R01 awards, Bioengineering Research Grants, and Bioengineering Research Partnerships, with the ultimate purpose of securing an NIH Center of Excellence award. If these efforts are successful, UVA will emerge as a critical node in the worldwide effort to diagnose and treat fibrosis.
The Prerequisites for Excellence
UVA has several key strengths that make it an ideal starting point for this initiative. First, it has assembled a diverse group of faculty with expertise in extracellular matrix (ECM) biology. This includes a core group in the Department of Biomedical Engineering that focuses on fundamental fibrotic processes, as well as clinicians and scientists in fields like pulmonology, cardiology, nephrology and microbiology who are investigating fibrosis in the context of specific organ systems or diseases.
In addition, UVA is internationally known for its strengths in computational and quantitative biology. The ability to model complex systems at multiple scales is essential to rapid advances in the field. The University also has exceptional depth and breadth in preclinical and clinical imaging methodologies. This includes such modalities as MRI, PET, ultrasound and such cutting-edge technologies as photo-acoustic imaging.
Thanks to the culture of collaboration that is such an integral part of UVA, we are confident that the Fibrosis Initiative will be able to direct the full range of expertise and breadth of technology on Grounds to address key challenges in fibrosis, while tapping existing partnerships with other institutions. The emphasis on translational research, reinforced by the Coulter Foundation Program in the Department of Biomedical Engineering, the activities of the Ivy Biomedical Innovation Fund, and the UVA Seed Fund administered by UVA Licensing & Ventures Group, will help ensure that breakthroughs in treatment will reach the public as quickly as possible.
A Three-Part Approach
These strengths will underlie efforts to produce a comprehensive analysis of the biomechanical and biochemical processes that lead to fibrosis. We envision biomedical engineers and scientists working in conjunction with clinicians to generate foundational insights that apply to a variety of clinical areas. Schematically, our approach can be divided into three, mutually reinforcing areas:
What are the extracellular biochemical and biophysical drivers of pathological cell behaviors and how might they change over time? There are a number of significant challenges to be overcome before researchers can quantify phenomena in the cellular microenvironment. In particular, there is a pressing need for tools capable of producing fine-scale measurements in all three dimensions and over time.
How do cells interpret and integrate extracellular signals into new activities and how might they impact neighboring cells? As the quality of data improves, the major milestones in our understanding of signaling networks will include accounting for heterogeneity among cells, integrating models of intracellular and multicellular communication, and developing techniques that make these models computationally tractable.
Can we nondestructively monitor diffuse and heterogeneous cellular and extracellular outcomes associated with fibrosis? There is both a clinical and an experimental need to harness to identify and leverage early molecular markers of fibrosis as well as develop new, more sensitive label-free imaging techniques that provide advanced detection and monitoring of fibrosis over time.