Translating research to make a difference
Having arrived in 1993 from Loyola University Medical School in Chicago, Mark Kelley is one of the longest-serving members of the Indiana University School of Medicine. Not surprisingly, his resume is filled with research accomplishments realized while working within the purview of IU School of Medicine departments and units such as the Wells Center for Pediatric Research, the IU Simon Cancer Center, and the IU Pancreatic Cancer Signature Center.
Kelley's interests, however, extend far beyond campus. He has successfully launched ApeX Therapeutics Inc., a biomedical company that aims to develop innovative new ways to fight cancer—and potentially other diseases—based on his scientific work.
"The reason Apex was formed was to translate our research to make a difference in people's lives," Kelley said.
Spun out of IU in 2008, Apex has raised more than $3 million in grants from the National Institutes of Health and the National Cancer Institute and funding from individual investors and venture firms, including Pearl Street Ventures and BioCrossroads.
Kelley is a recognized expert in an area of research involving a protein known as APE1, historically associated with the repair of damaged DNA. Kelley and his team were one of the first groups to demonstrate that the APE1 protein has an additional function: helping cancer cells "turn on" genes that regulate transcription factors that cancer cells need to survive. This work led Kelley to discover the novel use of a molecular compound known as APX3330, for which Apex plans to start a clinical trial in July.
"The ultimate goal of our research," Kelley said, "is to develop a drug that will help fight one of the toughest, most lethal forms of cancer, pancreatic cancer in adults, in addition to other hard-to-treat cancers in children."
But just getting to the first clinical trial is a massive achievement.
"After you have done all of the preclinical research and validated the target and the drug in the lab, you then have to design a clinical trial, scale up and make the drug to the quality standards for human use, get approval from the FDA to make sure that it's an appropriate trial to do in humans, and have the resources to conduct the studies. And all of that takes a lot of time, effort, and money," Kelley said. "It's really almost impossible to do it all in an academic situation. You really need a team of experienced people. And that's what Apex Therapeutics has done: It has helped take our discoveries and supported all the processes to advance APX3330 from the bench to the clinic."
As an undergraduate at DePauw University, where he majored in zoology and studied the genetics of fruit flies, Kelley first became interested in DNA repair pathways. He further pursued those interests at Louisiana State University, where he received his Ph.D., and at The Rockefeller University for his postdoctoral work.
"I was interested in a pathway called base excision repair, or BER," he recalled. "This is a repair pathway that fixes damage caused by a lot of chemotherapeutic agents, oxidative agents, alkylating agents. We thought it was a good pathway to study, originally in fruit flies and then in human cells. Following this pathway led me to the APE1 protein, where we discovered not only the role in DNA repair but also the secondary function involving the co-activation of oncogenic transcription factors that cancer cells need to survive and grow. This is a classic case of innovative research—following the science to a surprising result."
Nearly 30 years later, Kelley's single-minded focus is leading to results that he and his colleagues at Apex hope will result in new, potentially life-saving treatments for diseases that have devastated families and flummoxed scientists and doctors for generations.
"It's like any investigation, right? You start investigating the story. You're starting at one point and just following the leads where they take you," he said. "And so, by following the science, it's taking us to APX3330 and pancreatic cancer."