First NIBIB-Clinical Center Translational Research Fellow

Keeping a Foot in Both Clinical Radiology and Research Arenas

BY RAYMOND MACDOUGALL, NIBIB

A new fellowship program at NIH is making it possible for M.D.-Ph.D. radiologists to devote equal time to clinical care and research: the Clinical Translational Research Fellowship Program sponsored by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the NIH Clinical Center. The program’s first fellow is Michal Mauda-Havakuk, who has a Ph.D. in molecular biology and an M.D. from Tel Aviv University (Tel Aviv, Israel). She did a residency in radiology at Tel Aviv Sourasky Medical Center (Tel Aviv) and served as an attending physician before coming to NIH in 2017 to begin a radiology fellowship in interventional oncology. She transitioned to the new fellowship in summer 2018.

“Back in Israel, I looked for a unique fellowship that involved both research and clinical work,” Mauda-Havakuk said, adding that there are few such opportunities around the world. She wanted to do more than practice medicine based solely on prescribed clinical guidelines—she also yearned to make research advances that would lead to better treatments for disease. “I felt that interventional oncology—both research and clinical—would be a good fit for me.”

Mauda-Havakuk splits her time between the clinic and lab. “Every morning I go to the Interventional Radiology suite to observe procedures,” she said. “At around 2:00 p.m., I do research-related work. If we have experiments in the lab, I can do that. I feel it’s very flexible.”

Her current research involves developing an animal model for the study of hepatocellular carcinoma (HCC), a form of liver cancer. Each of the animal models—such as mice, rats, rabbits, and woodchucks—used to study the development and treatment of HCC has limitations, but woodchucks seem to be showing the most promise so far. “Woodchucks develop spontaneous tumors in their livers that resemble human HCC,” she explained.

She has several research papers in the works and is a co-author of a review article published in the May 2019 Journal of Hepatology, in which she and other NIH authors discuss animal models best suited to test combined immune-locoregional treatments for HCC; how tumor-cell death affects immune responses; the type of immune responses observed in patients treated with different types of locoregional therapies; and how to bridge the gap between interventional radiology and cancer immunology (J Hepatol 70:999–1007, 2019; DOI:10.1016/j.jhep.2019.01.027)

“It is rare to be at this intersection of clinical and preclinical work, where I think M.D.-Ph.D.’s have particular insight we can provide.” Mauda-Havakuk said. “We know the gaps, what we need, what patients lack, and the technologies we can promote—and then we go back directly to the lab where we try to find solutions. We know the available tools and can talk and work closely with engineers in our lab, whether software engineers, chemical engineers, or experts in other specialties.”

Among the tools that facilitate her research and clinical work are several 3-D printers, advanced-imaging facilities for people and animals, and a 28-color flow-cytometry system, which can analyze physical and chemical characteristics of cells or cell particles as they flow past beams of laser light. “The human resources here are even more amazing,” she added. “Everyone I’ve met and asked for guidance is extremely knowledgeable and friendly—and have inspired me to do anything that I would want to do.”

For example, when Mauda-Havakuk learned about thermosensitive liposomes—a type of nanoparticle that can deliver chemotherapy by heating targeted tissue—she was inspired to test the approach in pigs with bladder cancer and proposed that the therapy could be used to treat rectal cancer, too.

For the future, she plans “to maintain a foot in both [clinical and research] camps, pursue new treatments, and be innovative,” she said. “Everything that I do here I hope to carry on.”

NIBIB and NIH Clinical Center Translational Research Fellowship Program

BY RAYMOND MACDOUGALL, NIBIB

The NIBIB and the NIH CC Translational Research Fellowship Program is a collaboration between extramural and intramural scientists from NIBIB and radiologists and scientists from the NIH Clinical Center’s Radiology and Imaging Sciences Department. The one- to two-year program spans research in all aspects of clinical and basic imaging sciences, including clinical, translational, and basic imaging research. It has a unique focus on clinical translation and the training of clinician-scientists. Mentorship is provided by senior scientists and clinical investigators in radiology and imaging sciences.

“The new NIBIB-CC translational fellowship offers a truly unique way to offer bench-to-bedside—and back—training in translational research,” said Bradford Wood, director of the Center for Interventional Oncology and chief of Interventional Radiology at the NIH Clinical Center. The Center for Interventional Oncology is a joint effort of the NIH Clinical Center, the National Cancer Institute’s Center for Cancer Research, and, now, the NIBIB. “There is no better place in the world to learn the language of creativity via focused multidisciplinary team science,” he said. “This enables the development of practical solutions to unmet clinical needs—from conceptualization, to bench, to animal, to bed, to standard practice. The fertile interaction between bioengineer and clinician-scientist fuels the fire of innovation.”

Krishna Kandarpa, the director of NIBIB’s Research Sciences and Strategic Directions, wants the new fellowship to be “the nidus of change” leading to greater engagement between radiologists and engineers.

The fellowship program addresses low numbers of clinical as well as translational scientists in imaging and image-guided interventions—those who are ready to navigate from the bench to the bedside. The idea of a clinical translation and research fellowship was readily received by his colleagues at the NIH Clinical Center.

An ideal fellow would be someone “who bridges the engineering-physician gap—someone with an M.D. and a Ph.D. in the physical sciences or engineering,” said Kandarpa. A typical scenario would be for this individual to have a promising idea that they work to develop and translate to the clinic. Candidates could also have combinations of clinical radiology and math or computational science, which could lead to a project in artificial-intelligence application in radiology, such as accurate and reproducible imaging biomarkers of disease.

“Not every radiologist requires this training, but a good number of radiologists could benefit by it,” Kandarpa said. “They retain their roles as physicians, but also spend time guiding science and engineering development in medical imaging and image-guided interventions. My pitch to the Clinical Center was that these candidates should graduate from the program as potential stars in the field because, in addition to [having] a physician-engineer background, they would have proven bench-to-bedside research and development accomplishments.”

The fellowship can be a model that other institutions might replicate, said Kandarpa, emphasizing that a goal for the fellowship is to expand interest in the community, not just at NIH but elsewhere. “We’d like to create a process that encourages more radiology research. We figure that the nation’s biggest institute—a research institute and a hospital—can show that intramural, extramural, and clinical scientists can work together to create real advances through mechanisms like this fellowship.”

NIBIB’s Scientific Director Richard Leapman envisions that the fellowship program will provide an important link between the institute’s intramural researchers and radiologists in the Clinical Center. “NIBIB has some very creative basic and translational scientists who are eager for their work to find applications in the clinic,” he said. “Potential areas of collaboration could include development of novel molecular and nanoparticle-based imaging probes for [positron emission tomography, magnetic-resonance imaging (MRI), and computed tomography]; application of new approaches for accurate quantitation of MRI to give improved medical assessments, particularly for brain-related conditions; and harnessing of novel deep-learning approaches, which NIBIB is currently developing at the cellular scale, to application in medical imaging.”

“This fellowship is a key manifestation of the underlying team science culture at NIH,” said Wood. “Here, clinicians, basic scientists, and engineers with very different backgrounds, skill sets, and training are encouraged to stand arm in arm on a daily basis, in order to reach farther, think creatively, and together develop and translate bioengineering tools to address unmet clinical needs.”

Although only one fellow has been funded so far, ultimately the program could be expanded to fund a second or perhaps even a third fellow.

The NIBIB Clinical Translational Research Fellowship Program in the Clinical Center’s Department of Radiology and Imaging Sciences is accepting applications for one- to two-year fellowship positions. Applicants should hold an M.D. or an M.D.-Ph.D. degree and have completed training in radiology, nuclear medicine, biomedical engineering, or a related area of imaging sciences. For more information, visit https://www.cc.nih.gov/drd/training/index.html.