MD/PhD Student’s ‘Striking’ Study Makes Cover of Cancer Journal

Hailed by editors at Cancer Research as “striking,” Allen Chung’s study on early stage colon cancer marks one of the first times an oral biologic has successfully been used to change the natural history of a genetic disease.

The article appears in the journal’s Oct. 1 issue.

Using mouse models of precancerous polyps in the bowel, Chung and his team determined that certain types of immune cells within a chronically inflamed intestine can become rewired, causing them — paradoxically — to contribute to disease development rather than protect against it.

The researchers went on to reprogram these immune cells, making them lose their pathogenic potential.

How?

By delivering immuno-modulatory compounds — specifically, the bioactive protein interleukin-10 — into the inflamed intestine, they managed to reduce both the speed and severity of polyp formation.

This, in turn, lowered the mice’s disease burden and lengthened their lifespan.

“Site-specific oral therapy for intestinal disorders is a promising avenue of research,” says Chung, whose findings formed the basis for his doctoral thesis at UB.

“It avoids the use of systemic circulation and therefore minimizes the toxic side effects inherently associated with such a mode of drug delivery — most notably, liver, kidney and brain toxicity.”

Chung became interested in exploring the relationship between inflammation and polyp formation while studying in UB’s Department of Microbiology and Immunology. He began investigating how immunologic activity in the intestine may contribute to the development of precancerous polyps — or polyposis — within the bowel.

“It has long been known that inflammation within the colon increases the risk of developing colon cancer,” says Chung. Rates of colon cancer are much higher in individuals with inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis, than in the overall population, he notes.

“There are also genetic mutations that predispose individuals to develop colon cancer in early adulthood—and these individuals have been found to develop intestinal inflammation even before the appearance of their neoplastic disease.”

In addition to the article in Cancer Research, Chung’s thesis has led to a biomedical patent application and an invitation to participate in a multi-site national clinical trial of human polypotic disease.

“My time at UB has prepared me to conduct productive basic science laboratory research and handed me the tools to translate my findings into the clinic and establish my own translational research,” says the Maryland native, who defended his dissertation in 2013.

When Chung joined the MD-PhD Program in 2009, UB faculty helped him develop a personalized course of study based on his individual strengths, life experiences and professional goals.

“Since I came into the program with a significant amount of technical experience in my research field — for two years I worked full time as a research assistant in immunology at New York City’s Hospital for Special Surgery — the UB Department of Microbiology and Immunology allowed me to jump right into my research without having to complete redundant basic course material,” he says.

“As a result, I was able to finish my project in a little over two years.”

The MD-Phd faculty also allowed Chung to forgo several laboratory rotations so he could take part in a pediatric oncology education summer internship between his first and second years of medical school.

What’s more, Chung received permission to participate in longitudinal clinical inpatient services as a PhD candidate, albeit at a reduced intensity than what a typical third- or fourth-year medical student experiences.

“The MD-PhD program has been very supportive of my academic development throughout my time here at UB. The class size is small — there are only three to six students a year — and this affords a lot of individualized attention.”

Currently completing his medical education at UB, Chung expects to graduate with his combined MD/PhD in 2016.

From there, he plans to pursue residency training in internal medicine, pediatrics or obstetrics-gynecology.

“I'm very interested in becoming a medical geneticist or a specialist in reproductive medicine,” he says.

Chung is lead author on the study appearing in Cancer Research. His mentor, Nejat Egilmez, PhD, is now at University of Louisville.

Other study collaborators come from:

• UB’s New York State Center of Excellence in Bioinformatics & Life Sciences
• Roswell Park Comprehensive Cancer Center
• the Wadsworth Center (New York State Department of Health)
• Northwestern University
• University of Florida
• Brown University