Three University of Notre Dame faculty members—Basar Bilgicer, Bradley S. Gibson, and Paul Helquist—have been awarded grants from the Indiana Clinical and Translational Sciences Institute (Indiana CTSI) as part of the Collaboration in Translational Research Pilot Program. Another faculty member, Joshua Shrout, received a Young Investigator Basic Science award, and two graduate students—Apryle O’Farrell and James Clancy—have been awarded predoctoral fellowships by the organization.
Each of the CTSI-CTR teams, led by Bilgicer, Gibson, and Helquist, will receive $75,000 to conduct research and foster collaborations focusing on new medical treatments and services.
As part of his project, Bilgicer, an assistant professor in the Department of Chemical and Biomolecular Engineering and researcher in the Advanced Diagnostics and Therapeutics initiative at the University, is leading a multidisciplinary team of faculty from Notre Dame, Indiana University School of Medicine (IUSM), and Purdue University. These experts in bioengineering, chemistry, cancer biology, pharmacology, and clinical oncology are engineering nanoparticles to overcome drug resistance in multiple myeloma (MM).
The second most common type of blood cancer in the United States, MM remains incurable with a median survival of four to five years. Recent advances in treatment strategies and therapies have helped, but drug resistance remains an issue. Bilgicer and his team are designing nanoparticles that deliver chemotherapeutic agents selectively to the cancer cells while inhibiting drug resistance and reducing side effects. Their most recent work in nano-based technology has been printed in The Proceedings of the National Academy of Sciences and highlighted in the Harvard Gazette.
Gibson, an associate professor of psychology, is leading a study between the University and IUSM that seeks to compare the effectiveness of various working memory (WM) interventions for adolescents with attention-deficit/hyperactivity disorder (ADHD) and develop a more effective, and drug-free, treatment option.
Behavioral evidence suggests that individuals with ADHD have less WM capacity than those without the disorder, thus accounting for the inattentive, over-active, and impulsive symptoms associated with ADHD. A recent study conducted in Sweden indicated that an adaptive WM training regime (Cogmed-RM) could reduce ADHD symptoms, helping children function at a higher and more focused level. However, Gibson and Dawn Gondoli, also an associate professor of psychology at Notre Dame, have shown that the component of WM most improved by this type of training regime is different than the component of WM that is the most impaired in individuals with the disorder.
Through this project the researchers hope to create a more potent intervention by modifying the exercises used in the original training regime so that they have a stronger influence on those components of WM most impaired in ADHD. These efforts to develop alternative, experimentally-supported treatment options for ADHD are especially important because other recent long-term treatment studies have revealed serious limitations in the effectiveness of conventional treatments, such as drug therapies.
A professor of chemistry and biochemistry, Helquist is leading an interdisciplinary team from Notre Dame, IUSM, and Purdue to accelerate the transfer of a new class of anticancer drugs from fundamental research into clinical trials. The team is studying drugs that are novel compared to ones currently in use. At the same time, they are developing strategies for selective delivery of these new drugs to tumor cells by taking advantage of membrane receptors that are expressed uniquely by a tumor cell. By using this approach, the drugs should have little effect on normal cells, meaning that the commonly seen, undesirable side effects of chemotherapy can be avoided. Targeting these receptors can influence, or as the team believes, inhibit cancer progression, metastasis, and drug resistance. The fact that the drugs belong to a new class of therapeutics also extends the options that are available to a physician for the treatment of patients.
Team members include a clinical oncologist, a medicinal chemist and pharmacologist, and a synthetic chemist. They already have a proven track record of identifying distinctive mechanisms in breast and prostate cancer cells and will now be working to evaluate the metabolic stability of a specific cancer inhibitor in human plasma, as well as animal models. This is particularly important as a common obstacle in drug research and development is the failure of animal studies to produce similar positive results in humans.
Shrout, an assistant professor in the Department of Civil Engineering and Geological Sciences and member of the Notre Dame Eck Institute for Global Health, will receive support and research pilot funds in excess of $90,000 for his studies on the regulation and group behavior of bacterial surface swarming. Shrout and team are working to understand the cues that affect bacterial growth on human cells and identify the key environmental factors that could lead to better targeted drug therapies. Collaborators on this project include Jeffery Travers, the Kampen-Norins Professor and Chair of the Department of Dermatology at IUSM, and Clay Fuqua, professor of biology and associate chair for research at Indiana University at Bloomington.
O’Farrell, a graduate student in the Department of Chemistry and Biochemistry, is pursuing studies in the development of new antibiotics with Shahriar Mobashery, Navari Family Professor of Life Sciences. Clancy is studying the role that the small GTPase Arf6, a protein, plays in cellular events, such as the progression of cancer as it invades surrounding tissue and metastasizes. Both Farrell and Clancy will participate in a national research training program and complete the “Tools and Techniques in Translational Research” course through Indiana CTSI as part of their fellowship requirements.
Indiana CTSI is a collaborative effort of Notre Dame, Indiana and Purdue Universities, Clarian Health, BioCrossroads, private industry, state and local government, and others to implement a program of translational research, the process of turning basic scientific discoveries into new medical treatments and business opportunities, for Indiana.
Notre Dame’s Advanced Diagnostics and Therapeutics initiative is an interdisciplinary research initiative focused on developing diagnostic and therapeutic technologies for commercialization that reflect the University’s focus on research and support its mission to serve the greater good.
The Eck Institute for Global Health is a University-wide enterprise that recognizes health as a fundamental health as a fundamental human right and endeavors to promote research, training and service to advance health standards for all people, and especially people in low and middle-income countries who are disproportionately impacted by preventable diseases.