2023 Early Career Investigator Grant Recipient — Brooke Howitt, MD

Brooke Howitt, MD

Stanford University

Identifying the Cell of Origin for High- Grade Serous Carcinoma

Project Summary

The most common and most lethal type of ovarian cancer is high grade serous carcinoma (HGSC). However we now understand that the majority of “ovarian” HGSCs originate from the fallopian tube epithelium. This discovery was critical to understand that removing the fallopian tubes from women at higher risk for developing ovarian cancer can prevent the HGSC from occurring or remove cancerous lesions before they spread to other organs. There is a significant gap in knowledge regarding the specific cell(s) of origin for HGSC. Precisely defining the epithelial cells present in the fallopian tube is critical to our understanding of HGSC pathogenesis. In this project we are looking at individual cells from normal fallopian tubes removed from patients undergoing surgery for benign indications, to determine the specific cell types and states that are present in the benign fallopian tube and in early precursor lesions. To date we have examined over 350,000 single cells from 19 patients using cutting edge technologies. We will further probe the spatial organization of fallopian tube epithelial cells and integrate our findings with those reported in the literature, comparing age and hormone-related differences in cell types in the fallopian tube, and then we will apply this knowledge to generate “maps” of the cells in the fallopian tube, determine the cell types comprising early lesions, with the overall goal of identifying the specific cell types at risk for transforming to cancer.

This grant was made possible in part by a generous donations from George and Paulette Collias in memory of Matina, Georgiana and Cindy Gatziolis

Bio

Brooke E. Howitt, MD, is an Associate Professor in the Pathology Department at Stanford University. She received a BA in Biology from Washington University in St. Louis and then obtained her medical degree from Stanford University. Dr. Howitt then completed an Anatomic Pathology residency and the Women’s and Perinatal Pathology Fellowship at Brigham and Women’s Hospital where she subsequently was hired onto the faculty . It was during her time at Brigham and Women’s Hospital that she worked with Dr. Christopher Crum and developed a keen interest in the role the fallopian tube plays in “ovarian” high grade serous carcinogenesis.

Dr. Howitt’s research interests broadly defined focus on identifying pathologic and molecular features of gynecologic cancers and their precursors that can inform clinical diagnosis, prognosis, and predict response to treatment regimens. Her current focus is defining the cell(s) of origin for high grade serous carcinoma using cutting edge single cell analysis of benign, pre-malignant, and malignant fallopian tube epithelium.