Month in the Research Nexus leads to grant for TL1-KL2 research team

Each year, the South Carolina Clinical & Translational Research (SCTR) Institute offers “Month in the Research Nexus,” a required course for biomedical science graduate students in the SCTR TL1 Predoctoral Research Training Program and M.D./Ph.D. students in the Medical Science Training Program (MSTP) at the Medical University of South Carolina. In the month-long class led by Carol Wagner, M.D., and Perry Halushka,M.D., Ph.D., students design a clinical/translational research project from beginning to end, including writing the grant that could fund the project.

TL1 trainee Joseph Karam, who took the course during the Fall 2021 semester, can certainly attest to its value. He found out last month that he and his collaborator, Toros Dincman,M.D., Ph.D., an early-career investigator  in the SCTR KL2 (K12) Multidisciplinary Scholars Program in Clinical and Translational Science, had received a small grant from the Fred J. Brotherton Charitable Foundation for the project he designed in the class. That, in combination with future plans to apply for additional funding from Hollings Cancer Center, will provide Karam and Dincman with a budget to gather preliminary data for their work on pancreatic cancer.

“Their project highlights the unique aspects of the TL1 training program and the KL2 scholar program, which are now very well integrated,” said Halushka. “It is an exemplar of what we’re trying to do.”

Karam and Dincman met in the laboratory of Philip Howe, Ph.D., where they both work. The project, however, began in Spring of 2021 when Karam shadowed Dincman in his clinic. TL1 trainees are required to shadow a physician as part of their awards. Dincman, a gastrointestinal oncologist, sees many pancreatic cancer patients.

After their weekly clinic visits, Karam and Dincman discussed why efforts to improve treatments for pancreatic cancer have stalled.

“I asked him, ‘Why is the treatment for pancreatic cancer not improving? You see every type of cancer getting better treatments, but with pancreatic cancer, the survival rates have stayed stagnant,” said Karam. “We started talking about pancreatic cancer and had this idea about looking at the therapies, the stroma and then the genomic alterations that are there. That’s what our lab works on – looking at the genomics of cancer cells.”

Using pancreatic cancer tissue from the biorepository at MUSC, which also provides the clinical and treatment history of patients providing samples, Dincman and Karam will try to identify mutations and how they correlate with patients’ responses to therapy. They will also explore how tumor stromas, or cell matrices, change in patients with these mutations. The stroma is made up of noncancer and nonimmune cells that help to hold tumor tissues together. It is an important part of the tumor microenvironment, the area surrounding the tumor, that is often altered due to cancer.

“Changes to the tumor environment may be implicated in other downstream impacts, such as response to chemotherapeutic agents, the impact on survival with regard to metastasis or even recurrence after surgery,” Dincman explained.

The Month in the Research Nexus course provided Karam with the foundation to plan out the project, including the requirement to write a translational grant.

“The course was essential for refining this project and gave me the breathing room I needed to think the project through in terms of numbers, statistical significance and narrowing the scope of work,” said Karam.

Karam particularly valued the opportunity to work with biostatisticians to help him to refine his research question.

“We ran through our project with the biostatisticians, which is something I didn’t have prior experience with,” said Karam. “When I showed them our hypothesis, they said, ‘You really need to narrow this down into something that we can quantify and something we can have statistics for,’ which helped the project.” 

The class also provided students with the opportunity to write a grant proposal under realistic time constraints.

“It’s actually a pretty high-pressure class,” said Karam. “We had strict due dates for every section of our grant.”

In addition to grant writing, the course introduces students to other fundamentals of translational research. Students study topics such as populations, rigor and reproducibility, grant management and institutional review board (IRB) submission.

“The TL1 trainees find it a very rewarding experience,” said Halushka. “They have the opportunity to write a grant that translates their basic science discovery into a translational study in patients. They also begin to appreciate how to work with a physician-scientist, who serves as a mentor for their grant applications.”

Halushka also credits the course in part for the successful track record of MUSC’s MSTP and TL1 trainees.

“When the M.D./Ph.D. students interview for internships and residencies, they often talk about the Month in the Research Nexus and the grant that they’ve written,” said Halushka. “They will tell you that it really helps them get into some of the top internships and residencies in the country.”