Grants Program

The Basser Center for BRCA has the unique opportunity to catalyze research to change the paradigm of discovery, innovation, and care for issues related to BRCA1 and BRCA2 mutations. Germline mutations in BRCA1 and BRCA2 significantly increase the risk of breast and ovarian cancer and also are associated with prostate cancer and pancreatic cancer. Towards this end, the Basser Center is seeking applications that propose innovative approaches to the study of BRCA-related cancers.
 

The application period for 2025 is now closed.

The Basser Center for BRCA at Penn Medicine’s Abramson Cancer Center announces the Basser External Research Grant Program, which focuses on projects that have the potential to advance the care of individuals living with BRCA1 and BRCA2 mutations. Research grant applications in basic science, prevention, disease interception, and early detection and relevant to the study of BRCA1/2 will be considered. 
 

Funding: 

• One-year projects, up to $100,000 will be awarded. Six-month progress updates are required. A three-month notice of termination will be given if lack of progress is demonstrated. Final reports are required.
   

The application period for 2025 is now closed.

Angela Bradbury, MD
The eREACH study (A Randomized Study of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in Metastatic Breast, Ovarian, Pancreatic and Prostate Cancer Patients) will evaluate the effectiveness of a theoretically and stake-holder informed eHealth delivery alternative to traditional genetic counseling in patients with advanced breast and ovarian cancer. Dr. Bradbury expects this alternative delivery model for genetic testing has the potential to provide equal or improved patient outcomes, while reducing patient and genetic provider time and increasing uptake of testing in patients who can benefit from genetic testing. The study is anticipated to open in Spring 2019 and will recruit over 400 patients with advanced breast and ovary cancer.

Ronny Drapkin, MD, PhD
Animal models are the backbone of cancer research and can illuminate facets of tumor development, progression, and response to therapy. Robust models for ovarian cancer have been difficulty to develop in part because it is a very heterogeneous disease. The appreciation that the tumor microenvironment imposes constraints on tumor cell biology emphasize the need to develop models in an immunocompetent setting. The goal of this project, A Fallopian Tube Derived Syngeneic Mouse Model of BRCA-Related Ovarian Cancer, is to create such a model. To achieve this goal, the team isolated cells from the fallopian tubes (the primary site of origin for most BRCA-associated ovarian cancer) of immunocompetent mice and used genome-editing to create defects in key oncogenes and tumor suppressor genes that would allow for a tumor to form when the cells are implanted back into the abdominal cavity of the mouse. This enables the team to explore the specific contribution of BRCA mutations on disease development, progression, and how the microenvironment reacts to these tumors and whether the genetic makeup of the tumors (e.g., BRCA vs non-BRCA) influences those interactions. 

Roger Greenberg, MD, PhD
The Greenberg laboratory investigates basic mechanisms of DNA repair and their impact on genome integrity. These efforts focus on understanding how homologous recombination deficiency and DNA damage induced activation of immune responses contribute to breast and ovarian cancer etiology and therapeutic response. We utilize a myriad of approaches to investigate these areas, which include biochemistry, structural biology, cell biology, and genetically engineered mouse models. Our studies have revealed that BRCA1 recognizes ubiquitin and SUMO at DNA damage sites (Sobhian et al. Science 2007; Jiang et al. Genes Dev 2015; Zeqiraj et al. Mol Cell 2015; Jiang et al. JCB 2022), biallelic mutations in BRCA1 cause of a Fanconi Anemia subtype, FANCS (Sawyer et al. Cancer Discov 2015), and loss of the chromatin remodeling protein ALC1 potentiates PARP inhibitor responses by several hundred-fold specifically in HR deficient cells and overcomes known resistance mechanisms (Verma Nat Cell Biol 2021). This work led to development of ALC1 inhibitors that have entered clinical trials to overcome PARP inhibitor resistance in HR deficient cancers (NCT06525298). Our investigations have expanded to the question of how DNA double-strand breaks activate innate immune responses. We revealed the importance of mitotic progression and DNA and double-strand RNA pattern recognition to elicited anti-tumor immune responses (Harding et al. Nature 2017; Chen et al. Cell Reports 2020). Current studies leverage new methodologies we have developed to identify the endogenous DNA and dsRNA species that arise in BRCA mutant cells to activate anti-tumor immune responses. Postdocs will investigate basic mechanisms underlying this process and their impact on BRCA mutant cancer biology.

Katherine L. Nathanson, MD 
Dr. Nathanson’s research group works on multiple projects around hereditary breast and ovarian cancer, specifically in relationship to BRCA1/2.  First, her group has an on-going interest in identifying novel variants and genes associated with hereditary breast cancer.  More specifically, they are investigating non-coding region variants in BRCA1/2 (e.g. 5’ and 3’ UTR) to determine if they are associated with breast cancer, doing studies around identifying whether variants depending upon their type and location in BRCA1/2 have different risks of breast cancer, and participating in large scale consortium focused on identification of novel variant and gene discovery for breast cancer.  For these studies, they leverage the large biobank at Penn for hereditary breast and ovarian cancer, as well as the Penn Medicine Biobank.  With these studies, we also can characterize whether common variants are associated with differential risk in BRCA1/2 mutation carriers.  Second, her group has been working on characterizing the somatic and immune landscape of BRCA1/2 tumors for some time, and has put together a large sample set with whole exome sequencing, RNAseq and high throughput immunofluorescence (Fusion-Phenocycler), all matched with clinical data, in part through a collaboration with CIMBA. This large sample set is being leveraged for numerous analyses, with a priority on doing combination of multi-ome and immune characterization of the tumor samples; genotyping data also is available on many of these samples, with an interest in linking inherited variation to somatic genetics. Third, her research group is working collaboratively on a large pre-cancer atlas for BRCA1/2 mutation carriers, using single cell sequencing, high depth targeted sequencing and high throughput immunofluorescence among other technologies, in collaboration with several other groups.  Fourth, they are interested in understanding the immune function in patients carrying in BRCA1/2 mutation carriers, working with the immunology investigators at Penn. Dr. Nathanson’s research group is very collaborative, working with multiple investigators nationally and internationally on research efforts focused on the germline and somatic genetics of hereditary breast and ovarian cancer.  

Robert H. Vonderheide, MD, DPhil
The Basser funded study, TERT DNA Vaccination and Immune Modulation in a BRCA Mutant Mouse Model of Pancreatic Cancer, which is co-led by David B. Weiner, PhD (The Wistar Institute), is exploring the use of a TERT DNA vaccination in combination with immune modulation to prevent tumor development in a BRCA2 deficient pancreatic cancer model. This is a continuation of research that began during a Basser Team Science award, where the Weiner and Vonderheide laboratories collaborated to i) demonstrate synergy between TERT DNA immunization and immune checkpoint blockade in other tumor models, and to ii) develop a transgenic pancreatic ductal adenocarcinoma model lacking BRCA2 expression, termed the KPC-B model. In continuation of this work, this team will examine the impact of TERT DNA immunization either alone,in combination with immune checkpoint inhibitors targeting CTLA4 or PD1, or in combination with CD40 mAb or CD40L plasmid adjuvant using the KPC-B model. Their goal is to utilize these pre-clinical results to design a clinical trial for immunization of high risk BRCA1/2 mutation carriers.