Research

Ovarian Cancer Research Laboratory

Research Summary: 

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 scientists, postdocs, physicians, fellows, and students work together to answer important questions in ovarian cancer biology. We meet once/week to discuss research results and new ideas or listen to an invited speaker in our field. The laboratory is directed by Ernst Lengyel MD PhD, and Hilary Kenny, PhD. who 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 and the website of the Section of Gynecologic Oncology. Ernst Lengyel is 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, currently we believe that it is either in the fallopian tube or the ovary. Still cancer cells can also metastasize to the ovary giving the wrong impression that the tumor originates there. 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 from fallopian tube epithelial cells from tumors arising in the fallopian tube. 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 metastasizing to sites outside 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.

Main projects in the laboratory:

  1. Discover the cell of origin of serous ovarian cancer
  2. Understand the early steps of ovarian cancer metastasis to the peritoneum and omentum and study metabolic changes during metastasis
  3. Characterize tumor-stroma interactions in ovarian cancer, including the communications between adipocytes, fibroblasts, mesothelial cells, and cancer cells
  4. Use high throughput screening to identify novel treatments and evaluate the efficacy and mechanisms of new compounds in pre-clinical models to prepare for their translation to the clinic
  5. 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 novel organotypic 3D cultures with primary human omental cells (both normal and cancer-associated). We have also assembled several tissue micro arrays (TMA) with tissue from primary and metastatic ovarian cancers. 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 to inform what we do in the clinic and in the laboratory.

To reach our goals we have formed important collaborations with physicians and scientists. Our collaborators include:

The Peter Laboratory- Marcus E. Peter, Phd:  (miRNA and metastasis)
The Romero Laboratory- Iris Romero, MD, MS:  (Drug repurposing and the role of metformin in ovarian cancer, Metformin neo-adjuvant clinical trial) (NCT02122185).
The Mann Laboratory- T:  (Proteomics and ovarian cancer metastasis)
National Center for Advancing Translational Science  (NCATS) (High throughput screening)
The Moellering Laboratory-Dr. Raymond Moellering: (Metabolomics and ovarian cancer)
Dr. Samuel Volchenboum (Bioinformatics)
Dr. Ricardo R. Lastra (Gynecologic Pathology)
Dr. Josephine KimDr. Nita LeeDr. John Moroney and Dr. Diane Yamada  (Gynecologic Oncology Faculty at U of C)

The common goal of everybody working in our or with our laboratory is to transfer knowledge from the laboratory to the clinical arena, so patients may benefit and we improve survival of women suffering from ovarian cancer

See the NCBI listing of Dr. Lengyel's publications
See his citation index in Google Scholar 

We have job openings for technicians and postdoctoral scientists. Email us your CV if you're interested in joining our team: lengyeloffice@bsd.uchicago.edu

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 

 

Liu J, Eckert MA, Harada BT, Liu SM, Lu Z, Yu K, Tienda SM, Chryplewicz A, Zhu AC, Yang Y, Huang JT, Chen SM, Xu ZG, Leng XH, Yu XC, Cao J, Zhang Z, Liu J, Lengyel E, He C. m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nature cell biology. 2018; 20(9):1074-1083 The study is listed on the cover
See abstract.

nature medicine cover

Kristin M Nieman, Hilary A Kenny, Carla V Penicka, Andras Ladanyi, Rebecca Buell-Gutbrod, Marion R Zillhardt, Iris L Romero, Mark S Carey, Gordon B Mills, Gökhan S Hotamisligil, S Diane Yamada, Marcus E Peter, Katja Gwin & Ernst LengyelAdipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth Nat Med. 2011 Oct 30;17(11):1498-503 Cover article. See abstract

MCT civer

Zhang Y, Kenny HA, Swindell EP, Mitra AK, Hankins PL, Ahn RW, Gwin K, Mazar AP, O'Halloran TV, Lengyel E.

Urokinase plasminogen activator system-targeted delivery of nanobins as a novel ovarian cancer therapy. Mol Cancer Ther. 2013 Dec;12(12):2628-39 
An image from the paper was selected for the cover. See abstract

 

 

The Cover of the October 2007 International Journal of Cancer displays a picture of the 3D omental metastasis model created by the Lengyel Lab

Kenny HA, Krausz T, Yamada SD, Lengyel EUse of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells. Int J Cancer 2007;121:1463-72.
See abstract

Zillhardt M, Christensen JG, Lengyel E,.
An orally available small-molecule inhibitor of c-Met, PF-2341066, reduces tumor burden and metastasis in a preclinical model of ovarian cancer metastasis
Neoplasia 2010, 12:1-10. The study is listed on the cover.
See abstract

 

BBA cover

This cover displays a figure from 
Nieman KM, Romero IL, Van Houten B, Lengyel E Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013 ct;1831(10):1533-41
See abstract

Ernst Lengyel, MD, PhD

Arthur L. and Lee G. Herbst Professor of Obstetrics and Gynecology, Chairman of the Department of Obstetrics and Gynecology

 

Ovarian Cancer Research News

The Department of Obstetrics and Gynecology