By Steve Spencer
A revolution has been unfolding in the corridors of UAB, one that promises to reshape how we understand and treat disease. At the heart of this transformation stands the field of genomics where researchers are unlocking the secrets hidden within our DNA to bring hope to patients. Advances in the field are spurring a shift in medical thinking, moving from reactive treatment to predictive, personalized care.
“Genomic information can be used to help patients in a variety of diseases,” said Bruce Korf, MD, PhD, Professor Emeritus at UAB Genomics. “For instance, there are rare diseases that individually affect small numbers of people, while on the other hand, there are common conditions like diabetes and cancer, all of which have a genetic contribution.
“In the common disorders, the ability of genomics now to identify individuals who are at risk is rapidly improving to a point where we can imagine testing individuals who, at the point of testing, don’t have signs or symptoms, and we might see that their risk is increased and we would implement strategies to reduce that risk.”
Cancer, the second leading cause of death in American, is fundamentally a genetic condition. But the genesis of every cancer is the accumulation of genetic changes in the tissues that render those tissues exempt from normal controls on cell division. And categorizing the various genetic changes in these cancers is improving clinicians’ ability to customize treatment to the individual.
In the case of rare disorders, the contribution of genomics has been dramatic. For example, researchers have identified genetic modifiers that can affect the severity of sickle cell disease and are exploring the potential of gene editing therapies to correct the mutated gene in hematopoietic stem cells.
Likewise, genomics has made substantive improvements in autism spectrum disorder diagnosis. The field has witnessed a transformation from a time when establishing a diagnosis was possible in only 10 percent of cases to today’s reality where diagnostic rates exceed 30 percent.
“Now we have the ability to sequence the entire complement of genes, over 20,000,000 genes, and for that matter, all the DNA in the genome. And through that, we can identify genetic conditions that we previously didn’t even know existed,” Korf said.
The collaborative nature of modern genomic research has created unexpected connections across continents. Through systems like GeneMatcher, researchers can share findings globally, leading to remarkable discoveries about rare genetic conditions.
“We had an example of a genetic condition a while back now where we found something that was pretty obscure, put it into GeneMatcher,” Korf said. “Somebody in Germany turned out to have a very similar genetic change in the same gene. And when we compared their pictures, they looked so much alike that they could have been brothers. This kind of phenomenon is happening around the world.”
The practical applications of genomics extend beyond diagnosis to treatment and prevention. The state-supported Alabama Genomic Health Initiative identifies individuals at risk for various cancers and heart diseases, enabling intervention strategies that can prevent disease development or catch it in its earliest, most treatable stages.
“With cancer, as we categorize the different genetic changes that are driving a tumor, it reveals instances where there are drugs that you wouldn’t have thought of using that actually can make a huge difference in treating that cancer. And this is pervading all areas of medicine,” Korf said.
UAB is making an effort to expand personalized medicine, and genomics is a big part of that. “Dr. Nita Limdi, who manages the Alabama Genomic Health Initiative, has worked with her staff to do a pharmacogenetic analysis to identify genes that influence the way individuals metabolize drugs. They want to identify instances where you can avoid side effects and maximize the likelihood of benefit by matching the individual’s genetic profile to the medications they need to be on. She’s also involved in a National Institutes of Health program to test the ability to do genetic analysis to identify individuals at risk for a variety of common disorders and incorporate that into primary care,” Korf said.
The challenge ahead lies not in the technology itself, but in seamlessly incorporating these powerful tools into everyday medical practice. Most physicians today were trained before the genomic era, creating an educational gap that the medical community is working to bridge.
“As the use of these approaches increases over the coming decade, I think they will get blended into the fabric of day-to-day medical practice,” Korf said. “Medical providers will need to know when to use it and how it can influence decision-making. Our goal now is to make its integration as seamless as possible into the workflow of health care.”
As genomic medicine continues its rapid evolution, the ultimate goal remains clear: transforming the wealth of genetic information into better health outcomes for patients, one DNA sequence at a time.
