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Physician Resource

Researcher Highlight Q&A: Charles R. Farber, PhD, Orthopedic Genetics

Charles R. Farber, PhD, is a researcher focused on uncovering the genes that regulate complex diseases and the role they play within a systems-wide context. Farber is director of the Center for Public Health Genomics at UVA Health and a professor of public health sciences.

Using techniques like causality modeling between expression and physiological traits and generating disease-focused gene co-expression networks, his lab uses a systems approach to investigate the molecular basis of bone strength, with a goal of combining genetics and global gene expression profiling in mice to identify genes and pathways that influence bone strength.

See Farber's research interests and selected publications. Below, Farber discusses his research work and answers our Researcher Highlight questions:

What are you working on right now?

Osteoporosis is a disease marked by low bone mass leading to fragile bones that significantly impairs an individual's quality of life. My lab's research focuses on how genetics influences a person's risk of developing this disease. There is an intricate network of genes that plays a role in osteoporosis and we are just beginning to understand how genes impact bone health.

My lab employs state-of-the-art genetic techniques and tools to identify and understand the variation in genes that impact osteoporosis development and progression. We utilize the results of large genetic studies in human populations to identify osteoporosis-related genes, followed by laboratory methods to confirm their roles in bone. Our functional genomics studies aim to illuminate the function of these genes and how they interact with one another to increase an individual’s risk of developing osteoporosis.

Recent discoveries from our lab include the identification of several genes influencing bone strength. These findings serve to expand the current understanding of osteoporosis, providing a more complete picture of the genetic underpinnings of this debilitating disease.

What are the most intriguing potential clinical applications of your work?

Our work has the potential to lead to a number of future clinical applications. First, the novel genetic variants we've identified could inform the creation of predictive genetic tests. Such tests could identify individuals at an increased risk of developing osteoporosis early in life, enabling intervention strategies and personalized prevention plans.

Second, the genes we're investigating may serve as potential therapeutic targets. Understanding their roles and interactions could guide the development of new therapies that specifically target these genes or the biological pathways they regulate.

To be clear, while these clinical applications are exciting, they represent potential outcomes, and realizing them will require much more research. Nonetheless, they illustrate the promise that our research holds for improving osteoporosis management and care.

What recent discovery/paper/presentation has impacted the way you think?

I have been particularly interested in the work of Dr. John Morris and colleagues at the NYU Genome Center. They recently published a paper titled "Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens" in Science (4 May 2023, Vol 380, Issue 6646).

This research outlines a novel approach that merges two powerful technologies: CRISPR/Cas9 and single-cell -omics. CRISPR/Cas9 facilitates precise genetic alterations in cells, while single-cell -omics provides the capability to examine gene activity in individual cells.

Together they used these two techniques to understand the function of disease-associated genetic variants. These variants are often located in noncoding regions of the genome, which means they don't directly produce proteins but can still influence how genes function.

Their new method allowed them to identify the “target” genes whose expression was impacted by disease-associated variants — speeding the identification of potential new therapeutic targets. We are currently working with Dr. Morris to utilize this technique to identify target genes impacting bone mass.

What made you choose UVA Health as the place to do your research?

My decision was driven by several factors. First and foremost, the collegial and supportive environment of this institution. I firmly believe that success in research is highly dependent on collaboration, and UVA Health fosters a cooperative environment that stimulates intellectual exchange and the cross-fertilization of ideas. The colleagues I've had the opportunity to work with are not only exceptional in their respective fields but are also dedicated to sharing knowledge, which creates an enriching atmosphere for academic growth and advancement.

What do you wish more people knew about your area of research?

Osteoporosis is often underappreciated and seen as an unavoidable consequence of aging rather than as a serious and preventable disease. Yet, its impact on health, quality of life, and longevity is significant.

Across the world, an osteoporotic fracture occurs every 3 seconds. These fractures are not trivial — hip fractures, for instance, carry a mortality rate of up to 20% in the first 12 months after a fracture, and only 40% of those who survive return to their previous level of independence. In the United States alone, osteoporosis is responsible for 2 million broken bones every year, costing the healthcare system an estimated $25 billion.

Osteoporosis is called a silent disease because bone loss occurs without symptoms until the first fracture occurs. Many people remain undiagnosed and untreated because of this. However, with early diagnosis and the right treatment, the risk of future fractures can be reduced.

I strongly believe that greater public awareness of osteoporosis, its potential consequences, and its preventability could transform millions of lives. It's not just a matter of individual health — given the socioeconomic burden of the disease, addressing osteoporosis effectively could also have substantial societal and economic benefits.

How did you become interested in your area of research?

I received my PhD at the University of California, Davis. My doctoral research was centered on the genetics of obesity. Following my PhD, I had the opportunity to pursue a postdoctoral fellowship at UCLA. Although I initially continued to work on obesity genetics, early in my postdoc I had the opportunity to work on bone.

This unexpected deviation quickly captivated my curiosity. What I found fascinating was the dynamic nature of bone — a fact that is often overlooked. Did you know, for instance, our entire skeletons are replaced every 10 years? This is an essential mechanism to maintain bone health and repair damage from everyday wear and tear. This shift in focus led me to start my lab here at UVA Health focused on the genetics of osteoporosis.

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