2015 Mentored Investigator Grant Recipient — Xiaowen Hu, PhD
The human genome is made up of all the deoxyribonucleic acid (DNA) contained in our cells. Our DNA is made up of six billion individual DNA “letters” which are packaged into chromosomes. Just like the letters in a book make up words to tell a story, so do the letters in our genomes, which make up genes that ultimately produce proteins. In ovarian cancer cells, small changes in these genetic letters can significantly alter what a genomic word means. By studying the ovarian cancer genome, scientists can discover what letter changes are causing a cell to become cancerous. The sequence of a gene is like a language that instructs the cell to manufacture a particular protein or a functional ribonucleic acid (RNA).
There are two major steps in the translation of a gene to a protein: the DNA on which the gene resides is transcribed from DNA to RNA, and the RNA is then translated into a protein. Protein-coding RNA therefore 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 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, lncRNAs represents the cutting edge of cancer research. Investigation of the functions of lncRNAs in cancer will lead to a greater understanding of the molecular mechanisms of this disease, and should lead to novel clinical applications in oncology.
Our laboratory has long-standing experience in the investigation of non-coding RNAs in ovarian cancer. My studies have demonstrated that lncRNAs are altered in ovarian cancer with high frequency, strongly suggesting functional contributions of lncRNAs in ovarian tumorigenesis. Using a novel, clinically guided short hairpin RNA (shRNA) screening approach developed by our laboratory, I have successfully identified a potential oncogenic lncRNA, Focally Amplified lncRNA on Chromosome 1 (FAL1). I hypothesize that the lncRNA FAL1 plays a critical role in ovarian cancer growth, and that the investigation of the function of FAL1 may provide novel biomarkers and therapeutic targets for patients with ovarian cancer. The study intends to fill this gap by characterizing the molecular mechanisms, cellular functions, and clinical significance of a promising oncogenic lncRNA, FAL1, in ovarian cancer. The long-term gains from this research will be directly related to ovarian cancer patient care.
Dr. Xiaowen Hu is currently a research resistant professor in Department of Obstetrics and Gynecology at University of Pennsylvania. Dr. Hu got her B.S. degree in biology from Sichuan University, China and received her Ph.D. from Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences. Dr. Hu focused on the field of ovarian cancer research since she was a Ph.D. student. During her postdoc training at the Ovarian Cancer Research Center of University of Pennsylvania, Dr. Hu started exploring the genomics, epigenetics and no-coding genome of ovarian cancer. Her current research interest largely focused on the integration of cancer genome, epigenome, and computational biology, and then developing targeted therapy for ovarian cancer, especially, targeting the epigenetic modulators that significantly altered during ovarian cancer development and progression. Dr. Hu’s research has been supported by the Foundation for Women’s Cancer and Ovarian Cancer Research Fund Alliance. She is a previous recipient of Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund.