AMSR News

INTEL Semifinalist
Posted 01/17/2011 09:38AM

Jenny Quilty '11 of Massachusetts has been named as one of only 300 Semifinalists in the 2011 INTEL Science Talent Search Competition for her project entitled, “Identification and Characterization of Immunogenic Mutations in a Mouse Fibrosarcoma Model.” Jenny conducted her research with her mentor, Dr. Pramod Srivastava, during her junior year in a lab at the University of Connecticut School of Medicine in Farmington, CT. Jenny also worked very closely with Dr. Fei Duan.

Dr. Srivastava runs the Srivastava Research Group. Dr. Srivastava's laboratory research interests lie in four areas: antigen presentation by MHC I and MHC II molecules, immune response to cancer, viral immunity, and autoimmunity. The pursuit of these areas is linked to a key set of observations made by his laboratory over the past 20 years.  Click here to learn more about Dr. Srivastava.

Dr. Srivastava is effusive about his protegé. “She was superb! She questioned me often on other biomedical research problems and how the genomics work she was doing could be applied to them. Jenny is a very curious person. She was meticulous as an experimentalist. There was nothing mechanical about her approach to her work and she showed her creativity most clearly in thinking about the questions that I routinely posed to her. She also understood the limitations of the genomic approach to the question of identification of tumor antigens. Jenny recognized not just her own work, but how it fit into the overall scheme of the question.”

Dr. Duan echoed this praise. “All cells accumulate random mutations as they divide. Cancer cells accumulate many more. Such random mutations are unique for each tumor and often very immunogenic, which makes them perfect targets for new cancer immunotherapy. Finding those mutations that can be formulated into cancer vaccines has been a major obstacle for the field of cancer immunology. However, recent advances in deep DNA sequencing and bioinformatics make it possible. Jenny Quilty has showed in her INTEL article that immunization against one mutation in a mouse fibrosarcoma elicits strong and specific immune responses and more importantly leads to tumor rejection against a lethal challenge of the same tumor.

This study will not only help us to understand one of the most fundamental questions in cancer immunology, which is how immune system recognizes mutations in tumors, but also provide new theoretical and practical insights in delivering individualized vaccine immunotherapy to cancer patients in the near future. Jenny played a pivotal role in the project to identify novel targets for immunotherapy of cancer. I believe she will bring distinction to herself and the field in her future endeavors. “

Jenny has relished her experience in the Advanced Math/Science Research course. “I'd say that the entire experience has been incredible. While at times it was definitely difficult, I've learned so much, not only about my specific research but the dedication that goes into scientific research. My mentors, Dr. Srivastava and Dr. Duan were very supportive and helped me immensely along the way along with everyone in the lab and at Berkshire. My main goal was submitting a paper that I was proud of and when I did that in November, I was happy with whatever the outcome would be. Becoming a semi-finalist was an amazing reward for all of the hard work.

Jenny and Berkshire School will each receive an award of $1000. The 40 INTEL finalists will be announced on January 26th. Jenny is a member of the Advanced Math/Science Research course and is one of three Berkshire students to enter the contest this year.  Course Director Kurt Schleunes is proud of the success of his students. “We are just thrilled to have our students participating in the contest again this year. Only 1700 students from around the nation entered this year so it’s nice to see so many of our kids willing to step up and compete. Next year we will have seven entrants which is indicative of how the program has grown over the past few years. Jenny’s abstract is shown below:

It is estimated that there are about 3 tumor-specific MHC I-restricted epitopes per tumor cell. It has been proposed that these epitopes can provide immunotherapy benefits. Here, we look to determine all of the T-cell derived epitopes in a tumor, and synthesize them into a peptide in order to determine their immunogenicity. We use high-throughput sequencing to provide a basis for the mutations in a tumor, and then work to confirm these mutations, ultimately ending with analyzing the data developed by Sanger Sequencing. We have determined that 90% of mutations in a tumor, identified via high throughput sequencing can now be confirmed via Sanger Sequencing. The epitopes that develop from the confirmed mutations are then synthesized and immunized in mice. Four synthesized epitopes have been tested in vivo and have shown capabilities of generating an immune response. The responses have shown CD44+ IFN-γ+CD8+ markers between .4 and 1.2%, averaging at about .6 to .8%. One specific epitope has also proven to be a tumor rejection antigen. In mice immunized with the peptide developed from the epitope, 2 out of 3 mice tested showed tumor rejection in a prophylactic model. The development of individualized vaccine therapy may significantly enhance tumor suppression in cancer patients.

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