The annual Virginia Commonwealth University Massey Cancer Center Research Retreat showcases the most promising cancer research being conducted at Massey and throughout VCU and provides student researchers an opportunity to show off their contributions in the poster session, where they can receive up to $250 as Excellence in Cancer Research Awards winners. In addition to presentations from members of Massey’s research programs, this year’s keynote presentation featured Timothy Ley, M.D., who shared his work involving the acute myeloid leukemia (AML) genome.
The research program presentations this year were intended to highlight collaborative research projects that bring together investigators with different areas of expertise, with the goal of accelerating the translation of basic science to new therapeutic approaches. There was barely a seat left in the Molecular Medicine Research Building’s conference room as the retreat got underway. After brief opening remarks by VCU Massey Cancer Center Director Gordon Ginder, M.D., Matthew Hartman, Ph.D., from Massey’s Developmental Therapeutics program, and Lawrence Povirk, Ph.D., from the Radiation Biology and Oncology program, started off the lectures by discussing their collaboration on the development of a novel drug that could increase the effectiveness of radiation therapy by reducing cancer cells’ ability to repair DNA damage.
Next, Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program, chairman of VCU School of Medicine’s Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine (VIMM), presented on efforts to develop a viral gene therapy intended to induce expression of melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24 (mda-7/IL-24), which was originally cloned in Fisher’s laboratory and has been shown in experiments to kill a variety of different types of cancer cells at the primary tumor site and in distant, untreated tumors. The research was a collaboration between Fisher and Paul Dent, Ph.D., Universal Corporation Distinguished Professor for Cancer Cell Signaling, director and chair of the Division of Research in the Department of Neurosurgery at VCU School of Medicine and member of the Development Therapeutics program at Massey. Fisher discussed the entire process, starting with basic research findings and ending with efforts to initiate phase 1 clinical trials. He also commented on the challenges that face all cancer researchers attempting similar work.
Continuing on the mda-7 theme, Charles Chalfant, Ph.D., member of the Cancer Cell Signaling program, and Michael Shultz, Ph.D., from the Department of Biochemistry and Molecular Biology at VCU School of Medicine, presented their research on the connection between mda-7 and lung cancer. Chalfant and Schultz talked about findings from recent studies that have uncovered a novel regulatory mechanism that is “hijacked” by lung cancer cells and allows for resistance to current therapies. Furthermore, their research suggests that there is potential in developing a novel nanoparticle that harnesses both mda-7/IL-24 and reinstatement of the “highjacked” mechanism to effectively treat lung cancer.
Ley, Lewis T. and Rosalind B. Apple Chair in Oncology, professor of medicine and genetics and director of the Section of Stem Cell Biology at Washington University, and associate director of cancer genomics at The Genomics Institute, provided the keynote address on his work exploring the genetic changes that contribute to the development of AML. In 2008, Ley led a team that sequenced the full genome from a patient’s AML cells, making them the first to sequence an entire cancer genome. Whole genome sequencing is a process that can show all of the genetic components that combine to make a specific type of cell. Using the information they gained from sequencing AML samples, Ley and his colleagues were able to identify specific genetic mutations responsible for the development of AML. They discovered two key mutations, that are now being examined as targets for the development of new gene therapies. Ley also discussed future implications of genome sequencing in cancer research.
‌Every year, students in graduate level programs throughout VCU as well as postdoctoral fellows are invited to display their research relating to cancer and compete for Excellence in Cancer Research Awards. A panel of Massey judges awarded first, second and third place prizes totaling $250, $200 and $150 to students presenting the most promising cancer research. This year, nearly 60 research studies were on display throughout the halls and conference rooms of VCU Massey’s Goodwin Research Laboratory.
This year’s first place winner was Bridget A. Quinn, a student in VCU School of Medicine’s M.D.-Ph.D program. Quinn’s research focused on the potential use of a novel drug known as sabutoclax to treat pancreatic cancer, a disease for which there are few effective therapies. Quinn demonstrated that sabutoclax is capable of inducing apoptosis, a form of cell death, as well as growth arrest in pancreatic cancer cells. Further, she showed that sabutoclax, when combined with the commonly used antibiotic, minocycline, synergizes to produce profound growth inhibition and cell death in pancreatic cancer cells and mouse models.
Second place went to Chadia Robertson, a Ph.D. student in the Department of Human and Molecular Genetics at VCU School of Medicine. Robertson’s research focused on a gene, astrocyte elevated gene-1 (AEG-1), that has been shown to be over-expressed in many cancer types. In her study, she helped to develop the first mouse model that confirmed AEG-1’s role in the development and progression of liver cancer, a contribution that will be invaluable in future experiments testing new treatments for this disease.
Lauren Folgosa, also a student in VCU School of Medicine’s M.D.-Ph.D. program, received third place for her research that unveiled the effects of two genes known as ADAM10 and ADAM17 in the expression of tumor necrosis factor alpha (TNFa). TNFa is a signaling molecule that helps regulate processes essential to cancer cell survival, including inflammation, apoptosis and a variety of other biological functions. Using mouse models, Folgosa and her colleagues provided evidence of the processes by which dysregulation of the ADAM10 and ADAM17 genes impact the production of TNFa and lead to the development of cancer.