Rader Lab

Dr. Janet Rader, Professor and Chair of the OBGYN Department, has great interest in the care of women and research. Dr. Rader has a dedicated space in the Human and Molecular Genetics Center (HMGC) to further her research along with scientists, PhDs, RNs, technicians and data analysts.

Infection with high-risk human papillomavirus (HPV) is the primary cause of cervical cancer, but it is evident that additional events are involved in invasion and metastasis. Our laboratory employs a multidisciplinary approach for examination of both host and HPV genomic and epigenetic aberrations which may contribute to cervical cancer progression. It is our hope that these efforts may provide new targets for patient-tailored treatment strategies for women with cervical cancer and provide more meaningful prognostic indicators of clinical outcomes.

Defining HPV Integration for Identification of Novel Cervical Cancer Drivers: Integration of HPV into the host genome is thought to drive invasive cervical cancer via multiple mechanisms. One of our major research goals is to identify and characterize clinically-relevant genes/pathways from HPV integration signatures in cervical cancer that will improve individual treatment and outcome. We have recently began harnessing the data from The Cancer Genome Atlas (TCGA) project along with patient-matched long-read sequencing of HPV integration sites to define novel genes/pathways affecting cervical cancer outcome. In fact, our work on HPV integration spurred our interest in the long noncoding RNA, PVT1, as this gene was frequently targeted for HPV integration and had not been studied in the context of cervical cancer. Utilizing a variety of experimental methods, we demonstrated that PVT1 expression correlates with survival in cervical cancer patients, influences multiple cancer-related processes, and may contribute to chemoresistance. Thus, we expect that our ongoing annotation of HPV integrations cases will identify novel cervical cancer driver genes that we can subsequently test for functionality in vitro.

In addition to HPV integration patterns, our laboratory is also interested in other viral-based markers that may aid in development of reliable assays to assess cervical cancer patient prognosis. For example, we have recently published work demonstrating differential methylation of specific viral CpG sites in cervical precancer versus cancer. Further, our research has shown that specific HPV genetic variants associate with cervical cancer outcome. Collectively, our research on HPV integration and other viral biomarkers aims to find clinically-relevant prognostic and therapeutic targets for cervical cancer.

Other Research Interests: Developed and evaluating an 8-week summer program to train underrepresented minority students to work as clinical research professionals in complex multidisciplinary teams and prepare them for advanced degrees in cancer research. The program, Student-Centered Pipeline to Advance Research in Cancer Careers (SPARCC), engages students in real-world settings with diverse patient populations and provides additional career and education counseling opportunities. The program includes a Cancer Networking and Research Summit where students present a poster from their research work in the community.

Through a candidate gene approach that uses family-based controls, we identify inherited genetic polymorphisms and high-risk HPV subtypes/variants that contribute to the development of invasive cervical cancer and high-grade cervical intraepithelial neoplasia. The ongoing investigation is known as the Cervical Cancer Genetic Epidemiology (CerGE) study. We have DNA from cancer patients and family-based controls (trios), and have typed HPVs in tumors of affected women. To date, we have identified significant genetic polymorphisms in several candidate genes that associate with disease.

Froedtert Today - January, 2011

As seen in: Froedtert Today – January, 2011
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Future goals are to accelerate the identification of polymorphisms important in the host susceptibility to cervical cancer utilizing high-throughput genotyping and candidate gene sequencing. We will identify the causal basis of the variants by interrogating matched cancer samples and functional assays.

We want to understand why a small number of those exposed to HPV go on to get cancer.

Women who have been treated for cervical cancer may be eligible for a current study on genetic susceptibility to that cancer. Exposure to the human papillomavirus (HPV) can lead to cervical cancer, but it doesn’t always. “We want to understand why a small number of those exposed to HPV go on to get cancer,” said Janet Rader, MD, a Medical College of Wisconsin gynecologic oncologist, chair of the Department of Obstetrics and Gynecology and the study’s principal investigator.

The CerGE study, as it is called, has nothing to do with the patient’s treatment for cervical cancer. It is aimed at understanding both the HPV’s genetic variations and genetic variations in the patient that may cause cancer to develop in one person, but not another. As part of the study, Dr. Rader explained, the team also collects blood from the patient’s mother and father to examine which genetic variations the patient inherited and which variations they did not. The study’s results could help develop better testing for cervical cancer. Dr. Rader is especially interested in patients who have another first-degree relative — a mother or a sister — who also has been treated for cervical cancer. Please see more information on Dr. Rader’s lab.

More Information

For information on the CerGE research study, please contact the research team at 1-855-771-9477 or Email Us.

Rader, Janet S.,  MD

Rader, Janet S., MD

Chairman; Jack A. & Elaine D. Klieger Professor
Specialty: Gynecologic Oncology
Iden, Marissa, PhD

Iden, Marissa, PhD

Research Scientist - Dr. Rader's Lab
(414) 955-7413
Mutchler, Rachel

Mutchler, Rachel

Research Technologist - Dr. Rader's Lab
(414) 955-2279