Larry Matherly
Professor, Director T32 Training Grant, Cancer Biology Graduate Program
313-578-4280
Larry Matherly
Office Address
421 East Canfield, Room 3217.2
Detroit, MI 48201-1976
Mentoring
Austin Peterson
Department
Oncology
Research Interests
• Cancer metabolism
• Mitochondrial metabolism
• Folates and one-carbon metabolism
• Drug discovery
• Translational studies of chemotherapy response and resistance
Research Description
Research in the Matherly laboratory involves the membrane transport of folates, cancer drug development and discovery, basic preclinical studies of chemotherapy drug mechanisms and resistance, and translational studies of cancer with direct clinical application. The Matherly laboratory has long worked in the area of folate transport and one-carbon metabolism and has published extensively on these topics. Since we cloned the human reduced folate carrier (hRFC), the major tissue folate transporter, in the mid-1990s, the laboratory has been at the forefront of studies into the function, structure, mechanism and regulation of this physiologically and pharmacologically important transport system. In 2005, we directed a portion of our work toward the discovery and development of new folate-based therapeutics for ovarian cancer that selectively use folate receptor α without substrate activity for hRFC and that target critical one-carbon metabolic pathways. A recent aspect of this work involves targeting the folate receptor β-expressing tumor-associated macrophage population in high grade serous ovarian cancer. We extended our work to selectively targeting tumors via the human proton-coupled folate transporter (PCFT) for therapy which we found to be highly expressed in the majority of human solid tumors (including lung, pancreatic, colorectal and ovarian cancers) and is active at the acidic pH of the tumor microenvironment. Other studies focused on the biology and regulation of PCFT such that this might lead to new therapeutic approaches for treating conditions associated with folate deficiency (e.g., hereditary folate malabsorption) and further development of novel PCFT-selective tumor-targeted small molecule therapeutics. We have recently directed our studies toward a better understanding of one-carbon metabolism in the mitochondria and cytosol with the goal of identifying an entirely new generation of therapeutic agents that target both the tumor and the tumor microenvironment. In connection with these studies, we have extensively employed untargeted and targeted metabolomics including both 13C and 2H tracers to trace the relevant pathways. These studies have employed a range of tumor types including epithelial ovarian cancer, malignant pleural mesothelioma, non-small cell lung cancer, colorectal cancer and pancreatic adenocarcinoma. Translational studies have explored the relationships between glucocorticoids and pemetrexed therapeutic responses in lung cancer, and the complex interplay between Notch1 and AKT signaling in T-cell acute lymphoblastic leukemia including the relationship to Myc-driven mitochondrial C1 pathways.
Recent Publications
Education/Training
PhD (1981): Pennsylvania State University, State College, Pennsylvania
Courses taught by Larry Matherly
Spring-Summer Term 2025 (current)
Winter Term 2025
Winter Term 2024
- CB7210 - Fundamentals of Cancer Biology
- CB7240 - Principles of Cancer Therapy
- PHC7010 - Pharmacology Lecture