To better understand the genetics behind leukemia, Dr. Rao and his team use next-generation sequencing. A next-gen sequencer takes small bits of a patient’s DNA and sequences millions of fragments of it, with the hope of shining a light on which genetic mutations cause leukemia to develop. The bigger question, however, is: Which specific mutations are critical to causing cancer to form?  Investigators know that it usually takes two genes to cause cancer, but which ones? And how?

“My lab focuses on genetic interactions of different mutations,” Dr. Rao said. “How do you combine mutation A and mutation B, and do those two alone cause cancer? Do you need a third or fourth?” By better understanding which combinations of mutations cause cancer, investigators can better target them with new therapies.

Dr. Rao likens it to trying to play a movie in reverse. At the end, you know that one character falls in love with another. But what happened to get them to that point? The principle is the same in leukemia research. Investigators like Dr. Rao use experimental systems to try to recreate a patient’s history. They try mutation A, mutation B and so on down the line to figure out what caused cancer to develop. “If we understand how the tumor develops, then we can figure out ways to target it,” he said.

However, this research—which has the potential to affect patients of all ages, not just children—is still in its infancy. Though investigators are confident they know what the key “players,” or mutations, are, they need to figure out the sequence in which they interact to cause cancer to develop. In fact, Dr. Rao said investigators have been surprised by how difficult it has been to create models of leukemia. He said that they have combined mutations they thought would cause leukemia but haven’t. And the more mutations a certain type of cancer has, the more difficult it is to discover how they work together to cause disease. It will take many years to better understand these mutations and how and why they cause cancer. But Dr. Rao is perfectly poised to do so at Versiti Blood Research Institute.

“It’s a very collaborative environment with world-class scientists,” he said. “I like the opportunity to work somewhere where I can bring a unique expertise in terms of both leukemia biology and next-generation sequencing approaches.”

Dr. Rao’s expertise and knowledge of next-gen sequencing helps other investigators at Versiti Blood Research Institute better understand what causes a devastating leukemia diagnosis and enable them to develop new treatment methods for these patients.

Sid Rao, MD, PhD, is an associate investigator at Versiti Blood Research Institute.