Martin Matzuk Lab



2012 Collaborative Research Development Grant Recipient
Diagnostic Strategies for Detection of Ovarian Cancer

Project Summary
The early molecular events in the development of ovarian cancers are unknown, and there are no sensitive and specific screening tests for ovarian cancer. To address these issues, our multi-investigator and multi-institutional OCRF PPDG investigators have begun to develop animal models, strategies, and technologies to more precisely predict the early occurrence of ovarian cancers when the disease is surgically treatable. Our proposal includes three research projects and two cores. Project 1 is focused on the discovery of early protein biomarkers of serous ovarian cancers using a mouse model that recapitulates many of the steps that are observed in women with these cancers (Leader: Martin Matzuk; Co-Leader: Shannon Hawkins, Baylor College of Medicine (BCM)). Project 2 will define all of the proteins including variants that can be secreted from ovarian cancers and function as novel putative serum biomarkers (Leader: Laising Yen; Co-Leader: Matthew Anderson, BCM). Project 3 will use state-of-the-art equipment and technologies to identify the metabolic serum changes that occur when women develop ovarian cancer and evaluate the potential of this methodology to distinguish the different aggressive types of ovarian cancer (Leader: John McDonald; Co-Leaders: Facundo Fernández and Alexander Gray, Georgia Institute of Technology). In addition, our grant includes a Serum Core (Leader: Donna Coffey, The Methodist Hospital) and a Biostatistics and Bioinformatics Core (Leader: Chad Creighton, BCM) that will support this research program. The goal of our team is to develop integrated screening assays based on mixed small molecule/protein biomarker panels for detecting and distinguishing ovarian cancers at early stages in their development.

2007 Collaborative Research Development Grant Recipient
MicroRNA’s as Diagnostic and Therapeutic Targets in Ovarian Cancer

Project Summary
Traditional genes account for only about 2% of all human genetic material. Until recently, it was believed that the remaining genetic material acted as a scaffold. However, it has now become clear that DNA outside of traditional genes encodes small non-coding messengers known as microRNAs. Because microRNAs can regulate multiple genes simultaneously, changes in their expression can have far reaching biologic effects. We hypothesize that changes in microRNAs play an important early role in ovarian cancer. For our inter-institutional Ovarian Cancer Research Fund Program Project Development Grant, we have assembled an outstanding multidisciplinary group of oncologists, geneticists, and bioinformaticians to study microRNAs in ovarian cancer. Our scientific objectives have been to use state of-the-art DNA sequencing technology to identify the microRNAs that are upregulated and downregulated in ovarian cancer and to determine the consequences of these changes. With the support of the Ovarian Cancer Research Fund in 2009, we published a high profile paper in Endocrine Reviews entitled “The mammalian ovary from genesis to revelation”, we have our first paper describing our clear cell ovarian cancer work entitled “A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer”, (in press in Molecular Endocrinology), we submitted our first paper describing our work in serous ovarian cancer entitled “Molecular profiling uncovers microRNA-31 as a tumor suppressor in serous ovarian cancer”, and we have additional papers under review or in preparation.

These studies are leading us in new directions to develop novel therapies for treating ovarian cancers focused on the delivery of microRNAs both alone and in combination with known chemotherapeutic drugs.