Funded Research: 2017

Young Investigator Award
Kalpana Dorayappan, PhD
The Ohio State Comprehensive Cancer Center

Exosome Acute phase Proteins (APPs) as Potential biomarkers for early detection of ovarian cancer

Lay Summary: Ovarian cancer is the deadliest of the cancers of the reproductive organs in women in the United States and the main reason for that is there are no effective ways to find it early, before it spreads to other organs. Lack of effective screening methodology, lack of specificity and sensitivity in the existing cancer biomarkers makes this disease more vulnerable to delayed diagnosis and deaths. To acquire specificity in detection we propose that exosomes could be used as potential source of biomarkers and are a perfect fit for purpose’ because they reflect their originating cells increasing the specificity of the detected protein. Exosomes are small bubbles released by cells and can be found in blood and all other body fluids. These exosomes carry highly specific biological information from the cell of origin. In this study we are proposing plans to: 1) analyze the difference in the protein contents of the normal and tumor cell exosomes to find a “acute phase protein signature” 2) confirm the presence of those protein signature in serum exosomes from women with and without ovarian cancer by developing a exosome based protein test from serum that will favor the early detection of the ovarian cancer reducing the mortality rate.

Fiona Simpkins, MD
Ovarian Cancer Research Center
University of Pennsylvania

Exploiting DNA damage in Cyclin E high ovarian cancers

Dr. Simpkins is a physician-scientist in the Division of Gynecology Oncology at the University of Pennsylvania. Dr. Simpkins completed her OB-GYN residency at Johns Hopkins University and Gyn Oncology fellowship at the Cleveland Clinic Foundation. She completed a Cancer Research Training fellowship at the National Cancer Institute.  Dr. Simpkins’ research laboratory focuses on identifying novel targets and strategies to overcome drug resistance in ovarian cancer. Her laboratory has developed novel experimental models such as primary tumor cell cultures and over 50 patient-derived xenografts from ovarian tumors which have been characterized genomically and proteomically. This platform is used to understand mechanisms of drug resistance in tissue culture and test new targeted therapies. For her proposed study, she will test a novel therapeutic strategy that exploits the genomic instability of Cyclin E overexpressing ovarian cancers. Ultimately, Dr. Simpkins’ goal is to bring therapies with strong preclinical evidence learned in her laboratory to the clinic via phase I clinical trials.

Lin Zhang, MD
Ovarian Cancer Research Center,
University of Pennsylvania Perelman School of Medicine

Circulating long-noncoding RNA as an early detection biomarker for high-grade serous ovarian cancer.

Early detection of ovarian cancer will significantly improve patient outcomes. Screening and diagnostic methods for the detection ofovarian cancer include pelvic examination, transvaginal ultrasound, CA125 antigen levels as a biomarker and, potentially, multimarker panels and bioinformatic analysis of proteomic patterns. Although conventional strategies for bloodbased biomarker discovery (e.g., using proteomic technologies) have shown promise, the development of clinically validated cancer detection markers remains an unmet challenge for ovarian cancer. Protein-coding RNA serves as an “intermediate language” in the translation of a gene’s message into a protein’s amino acid sequence. In contrast, non-coding RNA refers to a functional RNA molecule that is not translated into a protein. Before the discovery of non-coding RNAs, the search for novel genes or biomarkers that drive the development of cancer was focused mainly on protein-coding genes. However, the human genome contains ~25,000 protein-coding genes representing less than 2% of the total genome, whereas up to 70% of the human genome is transcribed to RNA, yielding many thousands of non-coding RNAs. The recent discovery of non-coding RNA genes has dramatically altered our understanding of cancer. Thus, IncRNAs represents the cutting edge of cancer research. We hypothesize that certain IncRNAs can be an ideal class of blood-based biomarkers for the early detection of ovarian cancer, and the investigators at the University Pennsylvania have assembled a team with the expertise and resources to identify these novel circulating IncRNA biomarkers.