July 23, 2015 | by Amanda Traxler
Becoming what’s known as an independent scientific researcher is no small task, especially when working to translate research into meaningful health outcomes. Yet that independent status is vital, enabling researchers to lead studies and avenues of inquiry that they believe to be promising.
Clinicians, especially, can find themselves with little training in the intricacies of research studies and analyses.
“While training as a fellow, you are busy learning the clinical side,” said Joanne Mortimer, M.D., vice chair and professor of Medical Oncology & Therapeutics Research at City of Hope. “Having enough time to learn research so that you can be independent is not realistic.”
To bridge that gap, and help develop clinical scientists, the National Institutes of Health (NIH) offers mentored career-development awards, known as K awards, for young researchers and clinicians. These awards are intended to develop scientists who can be a connection between the lab bench and the patient bedside. That connection, and the people who create it, are at the heart of what’s known as translational medicine.
As a leader in translational medicine, City of Hope has been home to a significant amount of K12 funding – with the “12” referring to the method of distribution, that is, through the institution, rather than to individuals – for the past 20 years.
Mortimer is principal investigator and program director for the K12 program at City of Hope. In late June, City of Hope received confirmation of another five-year renewal of the extremely competitive grant, whose value Mortimer describes as being “an investment by the institution into the future leaders of oncology.”
Laleh Melstrom, M.D., M.S., an assistant clinical professor and hepatobiliary/GI surgical oncologist who joined City of Hope earlier this year, is one of the recent beneficiaries of the funding, bringing City of Hope’s current total of K12-funded trainees to five.
“It’s a once-in-a-lifetime opportunity,” Melstrom said of the grant, which gives her a chance to work alongside mentors John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy, and Don Diamond, Ph.D., chair and professor of the Department of Experimental Therapeutics, on a promising therapeutic approach to pancreatic cancer that targets tumors using an attenuated form of the Salmonella bacterium.
According to Mortimer, the best way to learn is on the job. The fact that the grants are connected to a specific lab – and, by extension, a mentor – ensures that learning happens.
“That’s where the mentors come in,” Mortimer said, “[they] help teach how to be a successful clinical translational researcher.”
Zaia, who has extensive experience in clinical trials, will work with Melstrom on opportunities to that end, Melstrom said, while Diamond, her lab mentor, “has an impressive track record” mentoring clinicians, “in addition to taking work in the lab to the bedside.”
Though K12 trainees work with patients, they must spend three-fourths of their time on research, which underscores why the award is so valuable in terms of becoming independent.
Melstrom calls her future research, which will be to characterize the histology and the mutational profiles of tissue samples, “a renaissance of sorts” for her career.
“We will be obtaining fresh tissue from patients who’ve had pancreatic surgery for cancer and growing them in vitro,” Melstrom said. “The cells will then be transplanted into mice to create patient-derived xenografts to not only test the salmonella therapy, but also additional future therapeutics.”
Mentoring too, is also a significant honor, says Mortimer.
“You have to have trained individuals in the past who have been successful, and of course you, too, have to have been successful.”
A case in point is Arti Hurria, M.D., a geriatric oncology researcher and current mentor who focuses on personalizing cancer therapies for older patients. Hurria’s work was largely kick-started by research awards —specifically, a mentored patient-oriented career development award, or K23. That award, said Hurria, who is director of the Cancer and Aging Research Program at City of Hope, “really formed the foundation for my future research.”
Hurria and her colleagues went on to develop a calculator to estimate an older adult’s risk for side effects from chemotherapy. Further, the research and mentoring from the K award formed the basis for a program of cancer and aging research with 23 studies that have specifically focused on older adults with cancer. Nine studies are currently ongoing.
“Since 2006, we’ve enrolled 2,942 older adults onto cancer and aging clinical studies,” Hurria said. In addition, Hurria helped set up a mentoring mechanism, the Cancer and Aging Research Group, for clinicians nationwide who want to improve care for older adults with cancer.
In short, the K awards benefit not just researchers, but patients, improving care for both individuals and overall populations.
“It’s all about passing it forward,” Hurria said, which is exactly what recent City of Hope K12 trainees are already doing.
Of the 11 who completed K12 training in the past decade, nine continue as City of Hope faculty.
“Unbelievably impressive individuals have completed this program,” Mortimer said.
Their success and productivity is evidenced by their high volume of published studies (115 studies, 45 of which are first-author reports), as well as the award of 93 grants. Nine of those grants are traditional research grants, called R01 grants, which come with substantially higher funding because they tackle bigger health issues with broader immediate impact.
As the original and oldest NIH grant, the R01 provides support to established (independent) scientists for health-related research and development. Those grants, according to Mortimer, are the K’s endgame.
“That is the absolute goal of it,” Mortimer said.
Current K12 (mentored clinical scientist development program) scholars
Joseph Chao, M.D., is an assistant clinical professor in the Department of Medical Oncology & Therapeutics, subspecializing in gastrointestinal malignancies. He will investigate primary tumor and circulating microRNA (miRNA) profiles in gastric cancer patients. These profiles may better characterize disease biology and serve as novel predictive biomarkers of drug sensitivity or resistance.
Alex Herrera , M.D., is an assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation. The focus of his clinical practice and research is immunotherapy and hematopoietic stem cell transplantation in patients with lymphoma. He will evaluate genomic biomarkers of response in patients who undergo CAR-T immunotherapy.
Laleh Melstrom, M.D., M.S., is an assistant clinical professor in the Department of Surgery, subspecializing in hepatobiliary malignancies. She aims to develop the potential of a Salmonella-based therapy against pancreatic cancer.
Daniel Raz, M.D., is an assistant professor in the Division of Thoracic Surgery. He will study the use of the drug triptoline as therapy for Wnt3a overexpressing lung cancers.
Yuan Yuan, M.D., Ph.D, is an assistant professor in the Department of Medical Oncology & Therapeutics specializing in breast cancer. She will test the efficacy of a novel therapeutic known as pegylated arginine deaminase, combined with doxorubicin, in women with metastatic HER2 negative breast cancer.
Other K Awards at City of Hope
K01 (Mentored Research Scientist Development Award):
Amy Y. Leung, Ph.D, is investigating the role of long noncoding RNAs in the development of insulin resistance and type 2 diabetes.
K99 (Pathway to Independence Award):
Ling Li, Ph.D, ultimately wants to create novel therapeutics for leukemia. His short-term goal is to establish a translational laboratory that provides an interface between basic biology and drug discovery. He is currently studying the role of the genes SIRT1 and p53.
Research pioneered at City of Hope and its renowned Beckman Research Institute has improved the lives of men, women and children throughout the world. Learn more about research at City of Hope.