Understand ovarian cancer biology and identify novel targets for treatment
The ovarian cancer laboratory at the University of Chicago, founded in 2004, is dedicated to improving our understanding of the biology of ovarian cancer metastasis and exploring the use of novel drugs for its treatment. We have created a very collaborative environment in the laboratory, so that postdocs, physicians, and students work together to answer important questions in ovarian cancer biology. We meet once/week to discuss research results and new ideas or to listen to an invited speaker in our field. The laboratory is directed by Dr. Ernst Lengyel (myself), and Hilary Kenny, PhD. We have worked together successfully since 2005.
Ovarian cancer is the 5th leading cause of cancer death among women in the United States, and has the highest mortality rate of all gynecologic malignancies. The high fatality of the disease is because it is often diagnosed at a late stage, when tumor cells have disseminated within the peritoneal cavity. Unfortunately, despite aggressive treatment, most patients have a recurrence and we are rarely able to cure the disease. For clinical information about ovarian cancer, please see the University of Chicago Medicine webpage discussing our treatment of ovarian cancer and ovarian masses. I am a clinically active Gynecologic Oncologist , with a special focus on the surgical treatment of ovarian cancer.
Although the cell of origin for ovarian cancer has not been identified, we now recognize that, after malignant transformation, tumor cells are carried by peritoneal fluid and attach to metastatic sites, including the peritoneum and omentum, rarely leaving the peritoneal cavity. The complex interactions between stromal and cancer cells control this dissemination. Therefore, understanding these bi-directional interactions has become a major goal of our lab.
For further overviews about ovarian cancer and specific areas of expertise in the laboratory please see our review article on ovarian cancer biology (American Journal of Pathology), or reviews on experimental models and 3D cultures in ovarian cancer, and the interaction between adipose tissue and cancer. See "Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer" Nature Reviews Cancer, which contains proposals by an international group of researchers for improving ovarian cancer survival
Main projects in the laboratory:
- Understand the early steps of ovarian cancer metastasis to the peritoneum and omentum
- Characterize tumor – stroma interactions in ovarian cancer, including the communications between adipocytes, fibroblasts, mesothelial cells and cancer cells
- Identify new treatment targets and evaluate the efficacy of these therapeutics in pre-clinical models to prepare for their translation into the clinic
- Investigate the validity of agents that are effective treatments in other cancers to delay or inhibit the development of ovarian cancer
- Utilize advanced proteomics analysis methods to gain further insights into ovarian cancer biology and develop tools for ovarian cancer detection and treatment
In our research, we use primary and cultured ovarian cancer cell lines and mouse models of ovarian cancer (xenograft and genetic). Interactions between cancer cells and the microenvironment are investigated in vitro using confocal microscopy (see our movie of a novel invasion assay) and novel organotypic 3D cultures with primary human omental cells (both normal and cancer-associated). We have also assembled several tissue micro arrays with tissue from primary and metastatic ovarian cancers. (see our video and article in the Journal of Visualized Experiments). These tissue samples are linked to a database containing clinico-pathologic information on all ovarian cancer patients operated on at the University of Chicago since 1992. Clinical data are collected prospectively. Recently we used proteomic profiling to identify the ovarian cancer cell lines that most accurately represent high-grade serous tumors at the protein level. This analysis revealed a protein signature that allows us to distinguish ovarian cancer tumors arising in the ovarian surface epithelium or fallopian tube epithelial cells from tumors arising in the fallopian tube. Dr. Watters and Dr. Lengyel are also exploring the use of serum proteomics to screen for ovarian cancer and differentiate between benign and malignant adnexal masses to avoid unnecessary diagnostic surgeries.
We cooperate very closely with the Department of Pathology at the University of Chicago, particularly with two Gynecologic Pathologists, Drs. Montag and Krausz. An important collaborator at Northwestern University is Dr. Marcus Peter in the Division of Hematology/Oncology and other important collaborators at the University of Chicago are Dr. Yusuke Nakamura in the Department of Medicine and Dr. Samuel Volchenboum, the Director of the Center for Research Informatics. A very close collaborator is Dr. Iris Romero, a Gynecologist who works on drug repurposing and ovarian cancer prevention. We also have a very productive collaboration with Fabian Coscia and Matthias Mann of the Matthias Mann Lab in the Department of Proteomics and Signal Transduction at the Max Planck Institute.
The common goal of everybody working in or with our laboratory is to transfer knowledge from the laboratory to the clinical arena, so that patients may benefit.
Please E-mail us with questions: email@example.com
Zhang Y, Kenny HA, Swindell EP, Mitra AK, Hankins PL, Ahn RW, Gwin K, Mazar AP, O'Halloran TV, Lengyel E.
Ernst Lengyel, MD, PhD
Section of Gynecologic Oncology
Department of Obstetrics & Gynecology The University of Chicago
In the News
Drs. Lengyel, Romero and Fleming are co-leaders of a project chosen by the Mayo Clinic Specialized Program of Research Excellence (SPORE). See Project #3
See the feature on the Lengyel lab's 3D model posted on the NIH National Center for Advancing Translational Sciences website: Stopping Metastasis in Its Tracks: New 3-D Cell Model Enables Closer Look at Cancer Progression
The Lengyel Lab rescently published a study, Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy, in Nature Communications, February 5, 2015
See a press release on the use of the 3-D model for high throughput screening on the NIH website