WHY DO SOME PEOPLE WITH EXCELLENT HEALTH HABITS still end up having heart attacks? Why do others who feast on junk food and never lace a sneaker live into their 80s and beyond? The answer to these questions may lie deep within our bones, where blood cells are born. It turns out that, as we age, these immature blood cells become genetically altered and grow uncontrollably as clones, wreaking havoc on the cardiovascular system. Scientists are hard at work trying to identify what triggers the rogue cells to undergo this clonal growth process, which is surprisingly frequent in elderly individuals. One man at the forefront of this emerging science is Ken Walsh, PhD, who directs the School of Medicine’s Hematovascular Biology Center. Here’s a deeper look into Walsh’s research in clonal hematopoiesis of indeterminate potential, or simply “CHIP.”
Q: CAN YOU BRIEFLY SUMMARIZE YOUR RESEARCH?
A: We’re looking at how mutations that accumulate with age within immature blood cells lead to an uncontrolled multiplying process that could be an important contributor to many chronic diseases, especially cardiovascular disease and stroke. Currently, the increase in these diseases and others as we age is considered to be unmodifiable. But, if we are right, it could be possible to identify and combat these age-dependent mutations within the cells that are responsible for the nonstop clonal growth. Already, we are studying one of the top mutated “driver” genes detected in white blood cells, which also shows a link to common blood cancers like leukemia.
Q: WHAT’S THE POTENTIAL FOR PATIENTS?
A: If we can identify the genes involved, then it becomes possible to develop a simple blood test that can more accurately predict who is at a greater risk for developing various age-related diseases. In turn, this could trigger preventive measures. As we continue to identify the genetic mutations involved in CHIP, we open the door to finding precise therapies to address them, potentially within drugs that are already on the market for other uses. Precision medicine, based on a molecular understanding of the genetic mechanisms at work, can help us specifically target the exact mutations causing the cells to clonally expand.
Q: WHAT ARE YOUR NEXT STEPS?
A: We are just at the tip of the iceberg. Currently, we are getting involved in clinical studies. For example, I want to conduct deep sequence analysis of people who have lived past the age of 100 to understand how these exceptionally long-lived individuals cope with this process. We are also conducting laboratory studies to identify more of the genes that drive the clonal hematopoiesis process and all of the diseases they may impact.
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