Dr. Vera Donnenberg and her lab's overarching goal is to translate basic research findings to therapeutic interventions. Dr. Donnenberg has predominantly led scientific advancements in the fields of therapeutic resistance in cancer, transplantation, and HIV. Her most notable scientific contributions are in the areas of cancer biology, adult stem cells, and lung and pleural immunopharmacology. Dr. Donnenberg’s independent research in the Department of Cardiothoracic Surgery demonstrates her decades-long commitment to translational research and her focus on investigating progression of thoracic malignancies, therapy resistance, and progression to metastatic disease.
Dr. Donnenberg’s career soared with her discovery of rare drug-resistant epithelial cells expressing mesenchymal markers CD90 and CD44 at the invasive edge of breast carcinomas (BC044784; 2019 Selected as the top 50 most influential articles in the Journal since 1963). As Co-PI on a grant award from the DoD BCRP, in collaboration with the Weinberg laboratory, Dr. Donnenberg has shown that CD90+CD44+ rare epithelial carcinoma cells are the de-facto metastatic seeds—also referred to as “cancer stem cells”—and they are the cells that uniquely interact with the surrounding microenvironment. As PI on an award from the DoD BCRP and in collaboration with the Wigler laboratories (at Cold Spring Harbor Laboratory, funded by the BC113183, VSD PI), she discovered that EMT tumor cells exist in a bi-directional state, transiting between epithelial and mesenchymal states, depending on signaling from the tumor microenvironment. Dr. Donnenberg’s complementary translational investigations in lung and breast cancer stem cells, the pleural environment, and human adipose tissue demonstrated that CD90 is a key marker of stemness and tumorigenicity. In non-small cell lung cancer (NSCLC), she described a C-KIT+ CD44+/CD90+ subset of NSCLC associated with invasion, metastasis, therapy resistance. In patients with resectable tumors, she identified the presence of these cells as an independent predictor of poor survival. In collaboration with the J. Peter Rubin laboratory, Dr. Donnenberg has shown that tumorigenicity of epithelial—but not mesenchymal—breast cancer cells is enhanced by coadministration of adipose stromal cells (via multiple grants and publication with the J.P. Rubin laboratory.
Dr. Donnenberg’s current investigations focus on understanding the normal and malignant pleural environment and its putative role in metastasis and therapy resistance. In her currently funded research (CDMRP BCRP BC210533 and BC211396, totaling to $2.3 million over 3 years), she concentrates on how hormonally positive (HR+) breast cancer metastasizes into the pleural space, becomes more aggressive, resists therapies, and causes malignant pleural effusions. These investigations will explain how this dramatic change in tumor behavior results from the interaction of carcinomas and the unique pleural environment, hypothesizing that the same physical barriers that protect the metastatic tumor can be exploited to concentrate antibody-based therapeutics within the pleural space, thereby breaking the cycle that supports invasive tumor growth and therapeutic resistance.