Cobalt(III) Schiff Base Complexes as Inhibitors of p53 Aggregation in Cancer
Abstract
Kaleigh Roberts is an MD/PhD student at Northwestern University. After completing her degrees, Kaleigh hopes to become a physician scientist, both leading a research lab and seeing patients at an academic hospital. Her primary research interest is studying the role of protein aggregation in disease. Her proposed research will develop cobalt-based compounds as inhibitors of protein aggregation. Recent work has demonstrated that mutations in the tumor suppressor protein p53 cause it to undergo amyloid aggregation and that this aggregation may explain how such mutations lead to cancer. P53 is mutated in over 50% of all human cancers, thus compounds targeting this protein have the potential for broad and significant impact on the study and treatment of cancer. The proposed research most directly falls under the Fiscal Year 2015 (FY15) Peer Reviewed Cancer Research Program (PRCRP) Topic Area of genetic cancer research, but due to the high prevalence of p53 mutations in cancer subtypes including colorectal cancer, kidney cancer, liver cancer, skin cancer, myeloproliferative disorders, neuroblastoma, pancreatic cancer, and gastric cancer, this work will be applicable to nearly all of the FY15 PRCRP Topic Areas. Kaleigh s training environment at Northwestern University will be invaluable to her development as a future cancer researcher and clinician. Northwestern Memorial Hospital is the #1 hospital in Illinois and one of the best in the nation, offering unparalleled access to clinical training in the diagnosis and treatment of cancer. Additionally, Northwestern is a world leader in biomedical research on cancer. Northwestern s Lurie Cancer Center is one of only 45 National Cancer Institute-designated Comprehensive Cancer Centers in the nation and a founding member of the National Comprehensive Cancer Network, an alliance of 26 of the world s leading cancer centers. As such, Kaleigh will have outstanding institutional support to develop as a future cancer researcher. As a scientist, Kaleigh has sought interdisciplinary training at the interface of chemistry and biology. She is completing her PhD in the Interdepartmental Biological Sciences (IBiS) program, which includes faculty and resources from molecular biology, chemistry, physics, computer science, and engineering. The IBiS program facilitates collaborations across multiple disciplines and provides a depth of training and scientifically creative environment not limited by the tools or techniques of a single field. Kaleigh is completing her PhD research in the lab of Professor Thomas Meade. Professor Meade is a leader in the application of inorganic chemistry toward the diagnosis and treatment of disease and has published numerous articles detailing the use of cobalt complexes as protein inhibitors. As a mentor, Professor Meade has enabled Kaleigh to grow as a scientist by providing training in many chemical and biological scientific techniques and affording her independence in experimental design and project construction. Kaleigh s proposed research involves the design and production of cobalt-based chemical compounds that can specifically bind to mutant p53 protein and prevent its aggregation. Decreased p53 aggregation should then lead to a decrease in cancer formation. As such, these chemical compounds will be useful both as potential therapeutics and tools for better understanding the biology of cancer. Because p53 mutations are present in nearly all subtypes of cancer, this research has the potential to be useful for a huge number of cancer patients. This research proposal outlines the initial design and synthesis of the compounds, as well as very early testing in cells taken from human cancers. If successful, further experiments testing the compounds in animals and eventually humans would be required for such a compound to be made commercially available as a drug. The timeline for drug development is variable, but slow, often taking around 15 yea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610379
Entities
People
- Kaleigh Roberts
Organizations
- Northwestern University
- United States Army