The problem: Blood stem cell transplant, which involves replacing damaged or diseased blood cells with healthy ones, can cure life-threatening diseases such as leukemia, lymphoma, multiple myeloma, and aplastic anemia. However, transplant patients face two common and often deadly complications: severe lung injury and a failure of the transplanted blood stem cell graft to “accept” the recipient’s body (graft-versus-host disease). Many of those patients are children.
“Patients can be cured of their underlying disorder and die of a related complication,” says Kenneth R. Cooke, MD. Cooke wanted to understand the cause of these complications and find ways to reduce their severity or, best case, prevent them.
Background: Kenneth Cooke’s skill on the football field provided important impetus to his career as a physician and scientist. Championship seasons as a receiver and defensive back during his high school years in West Paterson, N.J., led to an opportunity to play football at the University of Pennsylvania. One of five children of a water department laborer and a cafeteria worker, Cooke was the only one in his family to go to college.
Cooke went on to earn his MD at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, in Piscataway. He then completed a pediatric residency at the Children’s Hospital of Philadelphia before spending six years in Boston for his clinical fellowship and laboratory training in hematology/oncology at the Children’s Hospital of Boston and the Dana-Farber Cancer Institute.
While there, Cooke began studying severe lung injury and graft-versus-host disease in blood stem cell transplant patients under James Ferrara, MD. In experiments in mice, Ferrara and Cooke found that tumor necrosis factor alpha (TNFα), an inflammatory protein, contributed to both idiopathic pneumonia syndrome or IPS (a frequently fatal lung complication of stem cell transplant) and graft-versus-host disease (GVHD). When Ferrara moved to the University of Michigan and the C.S. Mott Children’s Hospital, he recruited Cooke to join him on the faculty there.
Making the connection with RWJF. Cooke first learned about the Robert Wood Johnson Foundation (RWJF) Harold Amos Medical Faculty Development Program (formerly the Minority Faculty Development Program) from colleagues at the Dana-Farber Cancer Institute. He applied for the fellowship following his move to the University of Michigan.
“I was focused on placing myself in the best position to become an independent investigator,” he says. “Obtaining research support at that point in my career was crucial.”
Cooke’s Native American heritage—his father was a member of New York State’s Saint Regis Mohawk Tribe—opened the door to the Amos fellowship, which Cooke started in 2001 and completed in 2005.
The project: Improving outcomes for stem cell transplant patients. The Amos fellowship helped Cooke continue his research, with Ferrara as his mentor. “When what drives a clinical problem is unknown, trying to untangle or solve that puzzle in the laboratory is the initial and necessary step to developing better clinical strategies,” he says. “The more you know about what drives a disease process, the better position you’re in to figure out how to prevent or treat it.”
Cooke tested Enbrel, a drug to treat rheumatoid arthritis and psoriasis that neutralized TNFα, to see whether it could treat the complications associated with blood stem cell transplants in mice. Results showed that Enbrel was effective in treating lung injury and GVHD in the mouse transplant models he developed (published in Blood, 2004;104:586–593; Transplantation, 2004;78:494–502; and Biology of Blood and Marrow Transplantation, 2008;14:385–396).
With support from the FDA orphan product division and the Leukemia and Lymphoma Society, Cooke and colleagues at the University of Michigan and the Dana-Farber Cancer Institute began conducting clinical trials in patients. Small studies in patients helped establish that Enbrel improves survival in patients with IPS (Blood, 2008 Oct 15;112(8):3073-81).
These encouraging results led to the development of two national, multi-center clinical trials examining the use of Enbrel as a treatment for IPS in adults and children. As of August 2013, Cooke and colleagues were analyzing the results.
“The results of our research have changed the way we approach patients with this disease,” says Cooke. But not all patients respond to Enbrel, so there is still work to be done. “The challenge,” says Cooke, “is to determine which patients are more likely to respond to this therapy while developing other agents for patients who might not respond. We continue to conduct research in these areas.” That research includes further analysis of results from earlier trials (Molecular & Cellular Proteomics, 2012; 11:M111.015479).
Moving his career forward. In 2007, Cooke joined Case Western Reserve University's Rainbow Babies and Children's Hospital, where he was the Ohio Eminent Scholar and Leonard P. Hanna Professor of Stem Cell and Regenerative Medicine, and director of the Pediatric Blood and Marrow Transplantation Program and the Multidisciplinary Initiative in Graft-versus-host Disease Program. His leadership resulted in tripling the number of transplant patients. Cooke also co-directed the Case Comprehensive Cancer Center’s Hematologic Disorders Program and directed or participated in several clinical trials.
Six years later, in 2013, Cooke became director of the Pediatric Blood and Marrow Transplantation Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “It is the top hospital in the country. The transplant program is very robust, and I have the chance to lead this program forward,” says Cooke, who is also the Herman and Walter Samuelson Professor of Oncology at the Johns Hopkins University School of Medicine.
Another reason Cooke was drawn to his current position is that Johns Hopkins is among the relatively small number of top-level institutions that focuses on translational research, in which scientists conduct cutting-edge research while also directly caring for patients. Cooke adds that his research gains momentum by taking information from clinical trials back for further testing in the laboratory.
Cooke’s research has been recognized by a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, a Clinical Scholar Award from the Leukemia and Lymphoma Society, and his induction into the American Society of Clinical Investigation.
Changing the standard of care. By continuing both his clinical and laboratory research at Johns Hopkins, Cooke hopes to continue to make new strides in treating the complications of blood stem cell transplants. His goal is to change the standard of care for stem cell transplant recipients who develop post-transplant complications. To some extent that ambition has been fulfilled: physicians around the world now use Enbrel to treat complications in blood stem cell transplants.
RWJF perspective: The Harold Amos Medical Faculty Development Program is a four-year postdoctoral fellowship launched by RWJF in 1983. Its purpose is to increase the number of faculty from minority and other historically disadvantaged backgrounds who achieve senior rank in academic medicine and dentistry. A commitment to eliminating health disparities is among the selection criteria.
The program supports one of RWJF’s major objectives: To increase diversification of the medical and dental professions and, as a consequence, improve the health care received by the nation’s underserved populations.
Of Amos program scholars, RWJF senior program officer David M. Krol, MD, MPH, says:
Ultimately, we would like to see these individuals from disadvantaged backgrounds becoming full professors at prestigious institutions, putting out important, valuable work, looking at a variety of different issues—including how to decrease the disparities between rich and poor, majority and minority—while climbing the academic ladder.
Kenneth R. Cooke is one of more than 185 Amos program alumni in academic medicine today. His career and research exemplify the academic achievement and professional contributions that the program was designed to stimulate.
“The measure of the success of the program is the success of the individuals” who participate in it, says Krol.
Kenneth Cooke, MD, on trail of great medical mystery - why are blood stem cell transplant patients dying?