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 a collaborative environment in the laboratory, where scientists, postdocs, physicians, fellows, and students work together to answer critical questions in ovarian cancer biology. We meet once a 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 – a clinically active gynecologic oncologist with a special focus on the surgical treatment of ovarian cancer; and Hilary Kenny, PhD – a Research Associate Professor whose work focuses on elucidating the role of the tumor microenvironment in ovarian cancer development and metastasis. Drs. Lengyel and Kenny have worked together successfully since 2005.

Ovarian cancer is the fifth 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 an incurable recurrence at some point in their cancer journey. For clinical information about ovarian cancer and ovarian mass treatments, please visit the University of Chicago Medicine’s Gynecologic Oncology webpage.

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 and 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, so understanding these bi-directional interactions is 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, immune, 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 human trials
  5. Utilize advanced transcriptomics and proteomics single-cell 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.
 

Collaborations:

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

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

 

Join the Ovarian Cancer Laboratory: 

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

1. The Ovarian Cancer Research Laboratory is looking for a Clinical Research Analyst I to join its ovarian cancer research team and support translational research. Some of the duties include consenting patients, processing and banking tissue and blood, protocol writing for clinical samples, database organization and identifying patients for translational research studies. The Clinical Research Analyst will work collaboratively with surgeons, fellows, nurses, principal investigators, and scientists. They will also help perform experiments.

External candidates (non-current University of Chicago employees) should apply using the following link: https://uchicago.wd5.myworkdayjobs.com/External/job/Hyde-Park-Campus/Clinical-Research-Analyst_JR15831

Internal candidates (current University of Chicago employees) should apply using the following link: https://workday.uchicago.edu/

  • Login with your CNet ID and password
  • Click on the “CAREER” icon
  • Next click on the “FIND UCHICAGO JOBS”
  • Search for JR15831

 

2. The Ovarian Cancer Research Laboratory is looking for a Research Analyst to join their team. Specifically, the Research Analyst will be investigating the role of the stroma and its therapeutic targets during ovarian cancer disease progression. This will involve human tissue, in vivo mouse models, and three-dimensional organotypic and primary cell models to perform translational research. The Research Assistant will work collaboratively with the principal investigators, fellows, students, and other research specialists. Under limited direction, the incumbent performs complex lab and/or wet lab research-related duties and tasks.

External candidates (non-current University of Chicago employees) should apply using the following link: https://uchicago.wd5.myworkdayjobs.com/External/job/Hyde-Park-Campus/Research-Analyst_JR15843-1

Internal candidates (current University of Chicago employees) should apply using the following link: https://workday.uchicago.edu/

  • Login with your CNet ID and password
  • Click on the “CAREER” icon
  • Next click on the “FIND UCHICAGO JOBS”
  • Search for JR15843

 

Funding:

2021-2028

R35 Outstanding Investigator Award

  • NIH/NCI Principal Investigator: E. Lengyel
  • Title: “Metabolic reprogramming of the tumor microenvironment and therapy resistance
  • Specific Aim: The goal of the proposal is to understand the role metabolism in tumor cells and the tumor microenvironment

2020 – 2025

R01 CA237029

  • NIH/NCI Principal Investigator:  E. Lengyel
  • Title: “Functional contributions of glycogen metabolism to ovarian cancer metastasis”
  • Specific Aim: The goal of this proposal is to understand if the microenvironment is regulating glycosylation of cancer cells.

2020 – 2023

Ovarian Cancer Research Alliance: Collaborative Research Development

  • Role: PI of Project #3: E. Lengyel. A joint application with Professor Balkwill (London) and Professor Cavallaro (Milan)
  • Title: “Interplay between ovarian cancer stem cells and the tumor microenvironment”

2020 – 2022

Chan-Zuckerberg Initiative

  • Principal Investigator:  E. Lengyel, Co-PIs: U of C faculty: Drs. Basu, Weigert, Chen
  • Title: A single cell atlas of the female reproductive tract
  • Specific Aim: Characterize all normal cells in the reproductive tract of postmenopausal women

2017 – 2022

R01 CA211916

  • NIH/NCI Principal Investigator:  E. Lengyel
  • Title: “Nicotinamide N-Methyltransferase (NNMT) as a master regulator of cancer stroma”
  • Specific Aim:  The goal of this proposal is to understand the role of NNMT enzyme in the metabolic reprogramming of tumor microenvironment.

2018 – 2021

Janet Burros Ovarian Cancer Initiative

  • Principal Investigator: E. Lengyel

2015 – 2021

P50 CA136393

  • NIH/NCI Mayo Clinic ovarian cancer SPORE PI: Scott Kaufmann. Role: PI of Project #7: E. Lengyel
  • Title: “Metformin as a metabolic target in ovarian cancer”
  • Specific Aim: To test clinically and pre-clinically the potential of metformin as a therapeutic in advanced, metastatic ovarian cancer.

2010 – 2021

Bears Care (NFL Chicago Bears)

  • Principal Investigator: E. Lengyel
  • Title: “Ovarian Cancer Drug Discovery by High-Throughput Screening with a Three Dimensional (3D) Culture”
  • Specific Aim: Determine if adipocytes contribute to ovarian cancer dissemination.

 

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Ernst Lengyel, MD, PhD

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

 

Ovarian Cancer Research News

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Cancer Ranked No. 14 in the country & High Performing in Ovarian Cancer Surgery in 2022-2023 U.S. News & World Report rankings

U.S. News & World Report ranks 10 University of Chicago Medical Center specialties among the best in the country

The Department of Obstetrics and Gynecology