Extended Benefits

NCI T32 training grants enable Ohio State to attract talented doctoral and postdoctoral students into research labs today and to mentor them as the cancer scientists of tomorrow.


Nadine Bowden is a young veterinarian working her way through a doctoral program at Ohio State to pursue her dream job: collaborating on preclinical studies of promising anticancer agents in transgenic mouse models. She is preparing to assess experimental agents for efficacy, antitumor effects and associated pathologies during preclinical testing, and to contribute to human risk assessments prior to phase I testing of agents.

Bowden’s specialized, interdisciplinary training is made possible by T32 grants, a National Institutes of Health funding mechanism that supports the training of doctoral and post-doctoral students for two to three years. Congress created these grants in 1974 to ensure that the nation has an adequate number of biomedical-research scientists.

A year into her pathology residency program, Bowden applied for a slot on the Oncology Training Grant, directed by Michael A. Caligiuri, MD, director of The Ohio State University Comprehensive Cancer Center and CEO of the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). She spent two years on the grant interacting with young physicians on the grant, attending a journal club and discussing clinical oncology research and cancer therapeutics.

Her doctoral research focuses on the human T-lymphotropic virus type 1(HTLV-1) and its role in the development of adult T-cell lymphoma. Her mentor is HTLV-I specialist Michael Lairmore, DMV, PhD, professor of Veterinary Biosciences and associate director for Shared Resources at the OSUCCC – James.

Bowden is investigating a protein called p30 that the virus produces to escape detection by the immune system. “Our ultimate goal is to find a target that will weaken the virus’s ability to evade the immune system,” Bowden says.

At the same time, she is studying mouse models through a training grant awarded to Lairmore titled Mouse Pathobiology: Models of Human Disease.

Bowden notes that one of the most important advantages of working on training grants is the people you meet. “I have interacted with investigators and trainees I probably otherwise would not have met, particularly when I was on the oncology training grant because the majority of those recipients were MDs.”

These grants also provide trainees with a salary and some funds to attend a conference and for research support. “It helps you transition from being a post-doc to having your own laboratory,” she says. Trainees go on to fill faculty positions at other universities or to work for government or industry.

More than 70 percent of T32 grants are awarded to National Cancer Institute (NCI)-designated Comprehensive Cancer Centers, such as Ohio State, which offer a multidisciplinary environment, well-equipped laboratories and faculty with wide-ranging expertise, says Linda Weiss, PhD, director of NCI’s Office of Cancer Centers. “And we want cancer centers training tomorrow’s cancer researchers.”

In 2010, the Cancer Training Branch spent about $166 million overall for training grants, with the T32 program receiving a little over a third of that, according to Ming Lei, PhD, chief of the Cancer Training Branch in NCI’s Center for Cancer Training.

“The National Research Service Award T32 program is the main NCI institutional training mechanism that supports the training of predoctoral and postdoctoral fellows,” Ming says.

For trainees, the benefits of T32 grants include a structured training environment, didactic courses, and an emphasis on interdisciplinary training and career development training, Ming says. “We encourage mentors to train fellows to manage career goals, to teach them how to obtain grants and progress from one career stage to the next, and to prepare them for an independent biomedical research career.”

“The program is also designed to promote diversity in the workforce among groups th at may be underrepresented in biomedicine, including the disadvantaged and the disabled,” says Sonia B. Jakowlew, PhD, a program director in the Center for Cancer Training.

The Soul of a Research Lab

Training grants not only prepare the biomedical researchers of tomorrow, they are vital to progress in cancer research today. “T32 training grants are enormously important because they provide an opportunity to recruit competent young researchers who bring with them new ideas and techniques,” says Albert de la Chapelle, MD, PhD, professor of Medicine and the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research.

A modern biomedical research laboratory typically includes a senior, or principal, investigator who heads the lab and spends most of his or her time writing grant proposals to obtain research funding, reviewing
data from current experiments and writing up research findings for publication in a journal, and one to several doctoral or postdoctoral students.

“It is the students who work for the principal investigator who are the drivers of the lab’s research projects,” says de la Chapelle, who also co-leads the OSUCCC – James Molecular Biology and Cancer Genetics research program. “Research ideas may come from the principal investigator, but the actual development and work of doing experiments comes from the doctoral and postdoctoral students. They are the soul of the lab. Every discovery is basically made by a post doc or a graduate student.”

“We want the brightest doctoral and postdoctoral students working in our laboratories today,” Caligiuri says. “They are the ones who are thinking purely science, and they are the ones who make the discoveries. Senior investigators will determine what to do with a discovery, but it’s the students who make the discoveries.”

Caligiuri offers an example from his own laboratory. Aharon “Ronnie” Freud was a doctoral candidate in Ohio State’s medical scientist program who discovered where immune cells called natural killer (NK) cells mature in the human body.

Freud had completed hundreds of hours of flow cytometry of NK cells, and his work revealeda  pattern that looked to Caligiuri as if the cells were trafficking to the lymph nodes. “I would never have guessed that,” Caligiuri says. “Ronnie obtained the code, and I deciphered the message. But the discovery was due to Ronnie’s persistence, energy, creativity and intelligence.” The finding was published in the journal Immunity (2005).

Caligiuri notes that training programs are peer reviewed every five years for the progress trainees have made. “There is tremendous pressure to provide a strong program,” he says. “If your trainees don’t succeed, your training program comes to an end. It’s a very good system.” 

From trainee to mentor William E. Carson III, MD, is a professor of surgery and breast-cancer specialist at the OSUCCC – James, and co-leader of the cancer center’s Immunology Research Program.

In 1991, Carson was a new surgical oncology fellow at Roswell Park Cancer Institute in Buffalo. He had a year of research experience and an interest in immune therapy for cancer, so his mentor encouraged him to apply for a slot in their T32 program.

Doing so would mean spending two years as a research fellow, along with two years as a clinical fellow. “At first I didn’t think that would be the way to go,” he recalls, “but I did it, and the training helped focus my career on academic surgery and prepared me to set up my own research laboratory. It gave me experience in the lab and data and papers that jump-started my research career. I also wrote a proposal and received a K11 award, which I wouldn’t have been able to do otherwise.” K awards are an NIH funding mechanism designed to help promising young faculty members establish their careers and laboratories.

Today, Carson has his own T32 grant to train postdoctoral students in immune therapy for cancer. Trainees participate in courses and meetings sponsored by the OSUCCC and the Immunology Program, and they are exposed to bioinformatics, human cancer genetics, translational medicine, experimental therapeutics and other related disciplines and receive training in responsible of human research.

“The overall experience helps trainees understand the translational potential of their discoveries, and it helps jumpstart their own research careers,” Carson says. Four students are on the grant at any one time, each working in their own area of interest under a research mentor.

Two for Translation

Sometimes NCI specifies the design of T32 grants; in other cases, investigators propose a design. The training grant in cancer genetics awarded to de la Chapelle, along with Gustvo Leone, PhD, OSUCCC – James associate director for Basic Research, and OSUCCC – James researcher Joanna Groden, PhD, professor of medicine, provides two mentors for every trainee. The main mentor is the head of the lab in which a trainee works. The other mentor is, when possible, a clinician who introduces the trainee to clinical thinking, clinical conferences and clinical research, including the role of Institutional Review Boards and ethical issues of human subject research.

“Many doctoral and postdoctoral students have little idea of the intricacies and hard work involved in collecting and storing clinical data and samples,” de la Chapelle explains. “We try to provide this.W e bring mentors and students together for a monthly conference to discuss topics related to translational and clinical research. The overall experience gives trainees insights into what is clinically important and what is not.”

Lairmore’s grant, Mouse Pathobiology: Models of Human Disease, recruits trainees from students who have entered the veterinary pathology residency program. It trains veterinarian scientists to understand and evaluate pathophysiologic alterations of murine models of human disease.

Trainees on the grant attend research seminars related to mouse physiology and models, they spend time at a major The Jackson Laboratory, a national center for mouse genetics and receive specialized training in laboratory animal husbandry. “These are also networking opportunities that connect trainees together,” Lairmore says.

“Their training leaves them with broad, comprehensive experience with mouse models and the ability to work with and guide medical oncologists on their hypothesis and on the best model to use,” Lairmore says.

They could help an investigator determine which cancer model best mimics the particular human disease they are studying. They could help them design the study, rank lesions and help interpret events during the study, along with others on the team, such as pharmacologists. “Some become comparative pathologists,” he says.

“My DVM training gave me a strong understanding of the animal as a whole, and my research training helps me understand the molecular basis of things,” Bowden says.

“My particular interest is drug development,” she continues. “If I can understand what the molecular biologists are doing, and I can also understand the laboratory-animal veterinarian’s concerns when testing a particular molecule, then it helps to ease the communication process and hopefully the process of drug development overall.”

The opportunity presented by her training grants, Bowden says, “has absolutely been a beneficial experience. I definitely recommend applying for a T32 if the opportunity presents itself.”

Pelotonia Training Grants

In addition to receiving federally awarded T32 traininggrants, the OSUCCC – James has established its own in-house training-grant program, which is supported by the Pelotonia bicycling fundraising event held by the Ohio State cancer program each August.

“The goal of the Pelotonia Fellowship Program is to get the best young minds at Ohio State involved in cancer research,” says director Jeff Mason, who notes that Pelotonia fellowships are available to undergraduate, graduate, post-docs in any of Ohio State’s __ colleges, as well as to medical students. In addition, the program is particularly timely because federal funding for training grants has remained flat for several years. In 2010, its first year, 70 fellowships were awarded: 29 to undergraduates, 22 to graduate students, 18 to post-doctoral students and one medical student. Awardees present their work at the OSUCCC – James annual research symposium.

“There is no other program that I know of like our one-year undergraduate fellowship program,” Mason says. “We are funding cancer-related research by trainees all over campus, including arts and sciences, communications and world literature in addition to projects in cancer prevention, survivorship, genetics, and population sciences.

Examples of undergraduate research projects include one to “Design Effective Anti-Smoking PSAs Targeting African Americans: A Dynamic Motivational Activation Model” by a Communications student, and “Targeting Protein Arginine Methytransferase 5 (PRMT5) Overexpression in Glioblastoma Multiforme,” by a Biochemistry major.

“Pelotonia fellowships offer a great opportunity for students and trainees, one that can help launch their career in cancer research,” Mason says, “and they are valuable to the rest of us because they help train the next generation of cancer researchers.”

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