2019 Early Career Investigator Grant Recipient — Kate Lawrenson, PhD
Project Summary
Epithelial ovarian cancer is a deadly disease. The majority of patients with high-grade serous ovarian cancer (the most common subtype) initially respond well to a combination of surgery and platinum-based chemotherapy. However, most patients develop platinum-resistant tumors for which there are few therapeutic options and, consequently, most patients with high-grade serous ovarian cancer die of recurrent disease within a few short years of their initial diagnosis and so there is an urgent need for new therapeutic options to better treat drug resistant disease.
While it is known that the gene expression signatures (transcriptomes) of ovarian tumors are very different from those of the normal precursor cells, the transcription factor proteins that orchestrate these gene expression changes are largely unknown. We are particularly interested in identifying the master transcription factors regulating the core regulatory circuit of HGSOCs, as we expect these factors to play crucial roles in regulating tumor cell survival. The overarching idea underlying this research is that by characterizing the master transcription factors driving ovarian cancer development we can develop effective targeted therapies for the treatment of these aggressive tumors. We developed a novel algorithm which enabled us to leverage data from 10,000 tumors representing 33 tumor types to identify candidate master transcription factors for ovarian cancer. We have identified a strong candidate master transcription factor, named SOX17, which is expressed in ovarian cancers and in ovarian cancer precursor cells, but lowly expressed in other tumor types. We propose that SOX17 becomes deregulated during tumor progression and so we will use a combination of in vitro modeling, in vivo models and state-of-the-art genomics technologies (‘ChIP-seq’ and ‘RNA-seq’) to comprehensively evaluate the role of SOX17 in ovarian cancer development. By the end of this this project we will evaluate SOX17 as a much-needed novel therapeutic target for treating HGSOC.
Bio
Dr. Lawrenson received both her bachelors degree with first-class honours and Ph.D. from University College London before relocating to Los Angeles to perform postdoctoral research at the University of Southern California. Dr. Lawrenson is currently an Assistant Professor in the Department of Obstetrics and Gynecology and the Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center. The Lawrenson lab has recently developed a novel tool – the Cancer Core Transcription factor Specificity (CaCTS) algorithm – to identify putative lineage-specific transcription factors in ovarian cancer. We are now characterizing how these factors drive the deregulation of ovarian cancer transcriptomes, with a particular focus on cancer-associated inherited and acquired genetic variants in the noncoding genome. Dr. Lawrenson’s research has been supported by an Ann and Sol Schreiber Mentored Investigator Award from the OCRA, a Cancer Free Generation Research Grant from the Tower Foundation, and a K99/R00 award from the National Institutes of Health. Dr. Lawrenson is part of the Ovarian Cancer Association Consortium (OCAC) and is an academic editor at PeerJ.