2023 Mentored Investigator Grant Recipient — Duaa Al-Rawi, MD, PhD
Ovarian cancer is the deadliest gynecologic malignancy and is characterized by alterations in DNA. This manifests itself as changes in both the numbers and structures of chromosomes which harbor the genetic material. Unlike normal cells, ovarian cancer cells exhibit a phenomenon called chromosomal instability. Cells with chromosomal instability often contain structures called micronuclei, which encapsulate entire chromosomes outside of the primary nucleus. We seek to learn how chromosomal instability shapes cancer cell behavior from the very early stages of cancer formation and the transition from pre-cancerous cells to invasive cancer. Preliminary findings in our laboratory have demonstrated that pre-invasive ovarian cancer does not exhibit chromosome instability. Yet, invasive disease ΓÇô even at its earliest stages ΓÇôbecomes progressively more unstable and contains micronuclei. Moreover, we have found that when chromosomes become encapsulated in micronuclei, they undergo significant disruption to their structure and organization leading to large scale reduction in gene expression. We propose to utilize patient samples and a cell-based model to understand the events that promote the transition from normal fallopian tube to pre-invasive disease to invasive high grade serous cancer. We will examine patient samples using markers of chromosomal instability, single cell studies and fallopian tube cells to examine how chromosomal instability shapes ovarian cancer cell behavior.
Dr. Duaa Al-Rawi completed her PhD in the laboratory of Michael Yaffe at the Koch Institute for Integrative Cancer research where she studied the biochemical function of BRCT domains. Her experience at the Koch Institute crystallized her desire to care for cancer patients and she transitioned to medical school at Stanford University after completing her PhD. She remained at Stanford for her Internal Medicine Residency and started Medical Oncology Fellowship at Memorial Sloan Kettering Cancer Center in 2020. Her clinical focus is gynecologic malignancies where she is mentored by Dr. Carol Aghajanian. Her research is focused on modeling and detecting early invasive ovarian cancer; she is jointly mentored by Dr. Sohrab Shah and Dr. Samuel Bakhoum. Dr. Al-Rawi is passionate about improving clinical outcomes of ovarian cancer through improved cell biologic understanding of the early drivers of ovarian cancer development.