PROFILES IN CANCER RESEARCH

Dr. Craig Jordan
Professor of Medicine, Department of Hematology/Oncology, James P. Wilmot Cancer Center



Dr. Craig Jordan

Dr. Craig Jordan has been studying human leukemia stem cells for a decade, using molecular and genetic analysis to identify characteristics that may extend the capabilities of personalized medicine. He is a patient, diligent pioneer in this effort. Adding to the challenge, he is working against a foe that is surprisingly elusive. For leukemia stem cells are in effect shape shifters, modifying their genetic code not only from person to person, but within a person and over the course of time.

“This is a very multidisciplinary problem,” he explained. “The last 10 years or so have been a really interesting time, and we’ve made a lot of progress. But I would say that we probably only have one chapter of the book on leukemia stem cells under our belt. There’s still a lot to learn.”

As a part of the University of Rochester’s James P. Wilmot Cancer Center, Dr. Jordan and his lab members collaborate closely with clinical research staff on site, conferring with them every day in what he describes as a highly collegial environment. “When you’re around the physicians who have these horribly sick patients, it’s hard not to want to do something,” he explained. “These are very bad diseases.”

Dr. Jordan briefly considered a career in medicine as a young man growing up in California. But after working in a research lab for several years after college, he decided that graduate school was a better fit. He entered the doctoral program at Princeton University with an interest in hematopoietic stem cells and went on to a fellowship at the Whitehead Institute. Several years after that were spent working in the biotech industry before he rejoined the academic ranks in 1997 at the University of Kentucky as an assistant professor of medicine.

Just a few years earlier, an important paper had been released in Nature by Dr. John Dick and colleagues. “That paper put leukemia stem cells on the map, in terms of characterization,” he said. “I was undifferentiated, if you will, at the time. And in Kentucky, I was working for the first time at a cancer center with physicians who were dealing with cancer patients on a daily basis. So the proximity to the clinical world and these newly characterized leukemia stem cells caught my attention.”

“The field was still very, very new,” recalled Dr. Monica Guzman, who came to the University as a graduate student from the Mexican city of León, choosing Dr. Jordan’s lab for her research. “We were essentially taking a shot in the dark, and there were a lot of people who questioned the concept of targeting leukemia stem cells. But now, things have turned out very well, and I think I made an excellent decision to join him in this project.”

Dr. Guzman says that Dr. Jordan’s patience and his ability to understand what each member of his laboratory needs to help them succeed have been special gifts to her in her career.

“His door is always open,” she said. “He’s given me a lot of independence in my research, but has offered more hand-holding for others when he thought that they needed it.”

Their big breakthrough came in 2001, when they released an article in Blood showing that the nuclear-factor kappaB (NFkB) molecular switch is activated in acute myelogenous leukemia stem cells. It revealed a vulnerable target for the disease. Now, Dr. Jordan is working with a company to test a plant-derived drug called parthenolide, which targets NFkB, in a phase I clinical trial. A number of other small molecules that target additional leukemia stem-cell characteristics are in the pipeline.

His ability to work so successfully with collaborators in government and with industry, including NCI’s RAID program, is uncommon for a basic scientist, said Dr. Allan Mufson, chief of the Cancer Immunology and Hematology Branch in NCI’s Division of Cancer Biology. “This puts him at the forefront of basic scientific investigators who are not clinicians, who have that stick-to-it-iveness to push something forward and get something in testing, because that’s difficult to do.”

Despite all of the success, Dr. Jordan acknowledged that there’s still a long row to hoe. “Nobody has really proven, yet, that we’ll be able to successfully treat more patients by targeting these things,” he said. “I hope that we’ll be able to really understand whether this treatment strategy is going to work within the next 5 to10 years, and I think that’s about the time frame that we’ll need to really figure it out.”

—Brittany Moya del Pino
http://www.cancer.gov/ncicancerbulletin/021009/page7