The scientific objective of the Basser Center for BRCA includes the funding of cutting-edge cancer research projects related to BRCA1/2 gene mutations ranging from basic science to clinical and translational research with an emphasis on collaborative projects shared between groups of scientists. To date, the Center has awarded over $15 million in internal and external grant funding to scientists at the University of Pennsylvania and around the world, including recent projects at Georgetown University, The Wistar Institute, Beth Israel Deaconess Medical Center, and Sheba Medical Center in Israel. More information on these grants can be found in the Current Grant Awardees section below.

This external grants program, unusual among scientific centers, is made possible by a $5 million donation in 2014 by University of Pennsylvania alumni Mindy and Jon Gray. Their total giving to Penn is $110 million, following a $25 million gift that established the Basser Center in 2012 and a $55 million gift to establish the Basser Cancer Interception Institute on 2022. The Center was created in memory of Mindy Gray’s sister Faith Basser, who died of BRCA-related ovarian cancer at age 44.

Internal Funding (for Penn Investigators)

Request for Applications: The Basser Center 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 Basser Center will review and consider any application on any area of research relevant to increasing our understanding of BRCA1 and BRCA2 and improving clinical care for individuals carrying BRCA1 and BRCA2 mutations. The newly funded Basser Cancer Interception Institute focuses on funding new endeavors in emerging fields beyond DNA damage. Example areas of research might include basic science of BRCA1/2 function, disease interception, translational and clinical research, and implementation science. Grants focusing on men & BRCA are encouraged. There are two types of awards available:

  • Request for Applications for Basser Faculty Research Awards: up to $200,000 yearly x 2 years
  • Request for Applications for Basser Early Career (Postdocs, Fellows, Instructors) Research Awards: up to $75,000 x 1 year

Eligibility:

  • Faculty applicants must be at the Research Assistant Professor level or above.
  • Early career applicants include Fellows, Postdocs and Instructors
  • Only one application will be accepted per investigator. Investigators may not be Co-PI on more than one application.    

The application deadline is now closed.

For questions related to the internal grants program, contact:
Beth Stearman, MPH
Administrative Director
Basser Center for BRCA
Phone: 215-349-8657
Email: stearman@pennmedicine.upenn.edu 

External Funding

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. The newly funded Basser Cancer Interception Institute focuses on funding new endeavors in emerging, orthogonal fields beyond DNA damage (e.g. mechanisms of haploinsufficiency, cancer evolution and tissue tropism). The current RFA welcomes submissions that are applicable to any of the topics listed above. Submission by early stage investigators is encouraged. This funding mechanism is not intended for Faculty at the University of Pennsylvania. Grants that demonstrate a potential for translation into clinical practice will be prioritized for funding.

Funding Level: 

  • Basser Innovation Award: 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 deadline is now closed.

For questions related to the external grants program, contact:
Cecilia Scavelli
Associate Director for Research Administration
Abramson Cancer Center
University of Pennsylvania
Email: cecilia2@upenn.edu 

Current Internal Grant Awardees

Identification of Uncharacterized Functional Non-Coding Variants in Breast Cancer Risk Genes
In this Basser Cancer Interception Institute (BCII) grant, Katharine Nathanson, MD and Yoseph Barash, PhD, are the Principal Investigators. Less than 10% of the individuals that undergo clinical genetic testing receive an explanation for their cancer or their family history of cancer, because their results are negative or uncertain. This initial one-year proposal leverages the existing Basser Center for BRCA sample set, existing and planned sequencing data generated by the Nathanson laboratory, and analytical expertise of Dr. Barash’s research group. Depending upon the data generated, additional years of funding will be proposed for further analysis and in-depth functional validation.

Pancreatic Cancer Interception Targeting Mutant KRAS
This grant is funded by the Basser Cancer Interception Institute (BCII) and is lead by Principal Investigators, Robert H. Vonderheide, MD, DPhil and Ben Z. Stanger, MD, PhD. Oncogenic KRAS mutations are found in more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC). Their goal is to determine whether KRASG12D inhibition can delay or prevent cancer development in the PDAC pre-cancerous setting (tumor “interception”). The team will also try to determine whether the addition of EGFR inhibition and/or immunotherapy can augment an ‘interception’ effect in this PDAC pre-cancerous model.

Vaginal Metabolome-Based Prediction of Ovarian Cancer
Maayan Levy, PhD, is the Principal Investigator of this Basser Cancer Interception Institute-funded study. Ovarian cancer is often referred to as the "silent killer" because of its mostly asymptomatic nature during early stages and the fact that it goes undetected until it reaches advanced stages. It is therefore critical to expand the search for specific indicators to help with early detection of the disease. In this study, researchers will examine the role of the microbiome and its metabolites in early detection and prediction of ovarian cancer development. The overall goal of this proposal is to investigate the involvement of the microbiome and associated metabolites in ovarian cancer and generate a predictive model for ovarian cancer risk and progression.

Using Protein Dynamics to Understand and Treat BRCA1-Mediated Cancers
In this grant funded by the Basser Cancer Interception Institute (BCII), the Principal Investigator, Gregory Bowman, PhD, has a goal to contribute to our understanding of and ability to treat BRCA1-mediated cancers by leveraging his lab’s expertise in protein dynamics through a combination of biophysical experiments, machine learning, physics-based simulations, and the world’s largest distributed computer. Dr. Bowman's team will work to identify cryptic pockets and design small molecules that engage these pockets to enhance interactions with binding partners like BARD, such that these structure-correcting molecules can be used to rescue pathogenic variants, and to infer the allosteric network that allows distal mutations to impact interactions like BRCA1-BARD binding, and test if this model can predict/explain the impact of other variants.

CDK7 Inhibition Suppresses Homology-Directed DNA Repair in Prostate Cancer
Irfan A. Asangani, PhD, is the Principal Investigator of this 2-year study focusing on metastatic prostate cancer. Metastatic prostate cancer (PCa) is incurable and the second leading cause of cancer death among men in the Western world. Although patients initially respond to androgen deprivation therapy (ADT), most eventually develop castration-resistant prostate cancer (CRPC) and metastasize to bone. His team will investigate the detailed mechanism of CDK7 mediated transcriptional axis that regulates the expression of BRCA1/2 and RAD51 for HR, R-loop accumulation, and cGAS-STING mediated inflammatory signaling in the context of PCa. Successful completion of the proposal will provide a robust framework for exploring PARPi in combination with CDK7i and immune checkpoint inhibitors as a viable therapeutic option in the treatment of refractory HR-proficient/deficient metastatic PCa.

Preclinical Development of a Novel ERISED Strategy to Overcome Acquired Resistance of PARP Inhibitor in Patients with BRCA Mutation
Principal Investigator, Lin Zhang, MD, intends to explore Poly ADP-ribose polymerase inhibitors (PARPis) that have been approved by the FDA to treat cancer patients with germline or somatic BRCA mutations. He will conduct a large-scale drug combination screen using chemical and genetic tools in a BRCA mutation setting that has acquired resistance, using a systems biology approach to characterize the mechanism of action for promising candidates with a focus on epigenetic regulation and immune responses. The team will then evaluate the identified combination strategy in preclinical models for treatment dosage and schedule. Finally, he will design and initiate an early-stage clinical trial in collaboration with clinicians and industry. Their proposed studies aim to provide a strong rationale for the clinical application of a combination of epi-drugs and PARPi in patients with BRCA mutations to overcome acquired resistance of PARPis.

Impacts of BRCA1 and spindle mechanics on chromosome instability
This early career award funds Geng-Yuan Cheng, PhD, Principal Investigator for this study. BRCA1 cancer cells are highly associated with chromosome instability arising from mitotic errors. Furthermore, although mitotic errors lead to genomic variability advantageous for cancer cell evolution, excessive errors are lethal, revealing vulnerability. This project will define the mechanisms of mitotic errors induced by mechanical disturbances linked to BRCA1 cancer progression. It will also reveal vulnerabilities to these disturbances by exacerbating mitotic errors. Overall, chromosome instability generates genome variability promoting BRCA1 cancer progression but also represents a potential vulnerability by excessive instability, so understanding physical factors impacting BRCA1 cancer cell division can guide therapeutic strategies. 

Sympathetic Innervention Inhibits High Grade Serous Ovarian Cancer Intestinal Metastasis in the Setting of BRCA1/2 Dysfunction
Matthew J Knarr, PhD, is the Principal Investigator in this early career award studying high grade serous ovarian cancer (HGSOC), currently one of the deadliest cancers diagnosed in women. It comprises most ovarian cancers that are diagnosed, and is the 5th ranked cause of cancer-related death in women. This study will test the hypothesis that BRCA1/2-deficient HGSOCs colonize the intestine surface through inhibition of local CCA nerve activity and reactivation of CCA nerve function can inhibit BRCA1/2-deficient cancer progression.

Development of an Organoid Platform for BRCA Mutant Ovarian Cancer
Fiona Simpkins, MD, is the Principal Investigator on this study funded to develop an organoid, patient-derived xenograft model (PDX) that will facilitate understanding of BRCA-related ovarian cancer from natural disease progression to therapeutics. The goal of these PDX models is to overcome mechanisms of drug resistance in BRCA mutant ovarian cancer, but thus far they have been challenging to develop. The study’s goal is to establish a robust organoid in vitro culture system using patient tumors from BRCA mutant ovarian cancers, with the hypothesis that developing a matched organoid-PDX model platform will allow for a better understanding of disease progression and improve the identification and streamlining of new active therapies from the lab to the clinic for BRCA related ovarian cancers.

Current External Grant Awardees

Defining the Pre-Clinical Treatment Regime of the Potassium Channel KCNN4 Inhibitor, Senicapoc, in BRCA1-Deficient Breast Cancers
Principal Investigator, Kara Britt, PhD, of the University of Melbourne, is funded to explore genome-wide association studies (GWAS) that have identified over 200 loci associated with breast cancer (BCa) risk, including the estrogen receptor (ESR1) locus. There is an urgent need to develop more risk reducing medications for BRCA1 mutation carriers as the uptake and adherence to endocrine therapy is very low, and prophylactic surgery is an unpalatable option for many women.

Improving the Scalability and Rigor of Expert Variant Curation
Melissa Cline, PhD, of the UC Santa Cruz Genomics Institute, is this grant's Principal Investigator. While an average woman in the U.S. faces a 13% risk of breast cancer and 2% risk of ovarian cancer in her lifetime, those numbers rise to a 50-75% risk of breast cancer and a 10-50% risk of ovarian cancer for women who carry pathogenic BRCA variants. This work stands to improve the rigor and efficiency of both Variant Curation Expert Panels (VCEPs), and in doing so, inform the clinical management of many more patients.

Modifiers of Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers of Asian Ancestry
Weang Kee Ho, PhD, of the University of Nottingham Malaysia, and Antonis Antoniou, PhD, of the University of Cambridge, are the Principal Investigators for this grant. Genetic and lifestyle factors have been demonstrated to modify breast cancer risk for women of European descent carrying BRCA1 and BRCA2 mutations. Given the strong evidence of changes in breast cancer incidences among mutation carriers over time, examining the shift in lifestyle/hormonal factors across generations can help to provide additional information on how these factors modify cancer risk in mutation carriers. The findings from this grant can help us to pave the way to provide more comprehensive genetic counselling for women carrying BRCA1 and BRCA2 mutations.

Targeting a New Class of Pathogenic Variations in BRCA1 and BRCA2
Principal Investigator, Georgios Karras, PhD, from the The University of Texas MD Anderson Cancer Center, is funded to study pathogenic variations in BRCA1 and BRCA2 which predispose to diverse cancers by compromising genome stability but also serve as useful targets for precision cancer therapy. This project will provide a conceptual foundation on which to study the role of HSP90 buffered BRCA1/2 mutations in inter-individual differences in susceptibility to cancer development and environmental sensitivity. It will also evaluate a new class of HSP90 modulators that could be useful for developing more efficacious intervention strategies for personalized prevention and management of diverse BRCA1/2 mutant cancers.

Deciphering the Immune Modulation by PARP Inhibitor and PD-1 Blockade in BRCA1-Mutated Mammary Tumors
Sven Rottenberg, DVM, PhD, Dipl ECVP from the University of Bern is the Principal Investigator of this grant. Poly (ADP-ribose) polymerase inhibitors (PARPi) lead to cancer regression of BRCA1/2-mutated tumors through synthetic lethality, but tumors eventually develop drug resistance and progress. This grant will aim to decipher the immunological mechanisms driving the benefit of the PARPi combo with anti-PD1. Special emphasis will be given to investigating the role of NK cells and neutrophils. This study will provide useful mechanistic insights to achieve the ultimate goal of developing immunotherapy approaches that reach high cure rates in patients with BRCA1/2-mutated breast cancer.

The International BRCA1/2 Carrier Cohort Study (IBCCS): Prospective Cohort Analyses
Principal Investigator, Yen Tan, PhD, MSc, BSc, from the Medical University of Vienna, is funded to follow a prospective cohort of BRCA1 and BRCA2 pathogenic variant carriers from the International BRCA1/2 Carrier Cohort Study (IBCCS). The purpose of the current proposal is to update the central IBCCS cohort with the additional 10 years of follow-up data that have been accrued and the additional carriers recruited since 2013.

A Short Treatment to Intercept Nascent BRCA1/2 Breast Cancers
Gerburg Wulf, MD, PhD, of the BIDMC/Harvard Medical School, is the Principal Investigator of this grant that will study the feasibility of a short-course treatment to eradicate early BRCA1/2 mutation tumors at or below the threshold of detectability. The findings in this proposal will provide the rationale for a time-limited, preventative oral treatment that may be an option for BRCA1/2 mutation carriers who wish to reduce their risk.

Basser Core Investigators

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 goal of this study, BRCA Function in the DNA Damage Response, is to identify and target mechanisms of resistance to PARP inhibitors (PARPi) and Platinum based chemotherapies in BRCA1 and BRCA2 mutant cancers. This work has led to the initiation of clinical trials using approaches to identify patients that are more likely to respond to PARPi therapy. Dr. Greenberg’s lab has made substantial progress stemming from their discoveries as part of their earlier team science grant. The team defined alternative pathways to BRCA-Rad51 recombination that are required for survival in BRCA mutant cells. They have also identified the entire network of these alternative DNA repair mechanisms, providing a rich source of factors to investigate in BRCA mutant cells that have become resistant to PARPi. Another aspect of the research comes from discovery of a new gene that is required for survival of BRCA mutant cells and dramatically increases their sensitivity to PARPi. This work is a promising avenue to begin drug discovery efforts.

Katherine L. Nathanson, MD 
The team's projects, including Phenotypes of BRCA1/2 Mutation Carriers From Population Based Databases to Tumor Development, focus on understanding the phenotypes associated with BRCA1/2 mutations, in particular related to genotype-phenotype correlations. This on-going project analyzes primary BRCA1/2 mutation-associated breast cancers to evaluate whether molecular and pathological features vary between breast tumors associated with different mutational types (missense, large genomic rearrangements vs. frameshift/truncating) and locations (exon 11 vs. non-exon 11). They also are interested in examining the Penn Medicine Biobank to determine whether mutation type and location can be associated with clinical features. They continue to evaluate whether allele-specific loss of heterozygosity is associated with outcome and are using a large well characterized sample set to do so. They are evaluating matched primary and recurrent BRCA1/2 mutated breast and ovarian cancer to identify recurrent specific features that can potentially be therapeutically targeted. We have identified several potential features that may be of interest, including some that are associated with significant differences in survival, but the results are preliminary and need further validation.

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.

Gray Foundation Grants

Basser Center founding donors, Mindy and Jon Gray, have established the Gray Foundation with the mission to transform the lives of individuals born with BRCA mutations by accelerating research into BRCA-associated cancers. The Gray Foundation is committed to health equity and values diversity and inclusion in its funded research programs. To read more about the Foundation and current grant funding opportunities, click here.

Past Grant Awardees

Recent grants are listed below. For the full list and descriptions of all past grants, click here.
 

Internal Grants:
 

  • Elucidating the Roles of Ubiquitination in Homologous Recombination
    Principal Investigator: George Burslem, PhD
  • Leveraging the Electronic Health Record to Promote Guideline-Recommended Cancer Risk Management in BRCA1/2 Carriers
    Principal Investigator: Kelsey Lau-Min, MD
  • The Role of Pattern Recognition Receptor-Driven Inflammation in BRCA-Deficient HGSOC
    Principal Investigator: Timothy Lippert, PhD
  • Risk Stratification Among Known BRCA1/2 Mutation Carriers Using Polygenic Risk Scores and Imaging Biomarkers
    Principal Investigators: Anne Marie McCarthy, ScM, PhD, and Despina Kontos, PhD
  • Molecular Mechanisms That Regulate PARP-1 and Impact its Effective Targeting in Homologous Recombination Deficient Cancers
    Principal Investigator: Nootan Pandey, PhD 
  • Insurance Barriers to PARP Inhibitors in Women with BRCA1/2 and Ovarian Cancer
    Principal Investigator: Anna Jo Smith, MD, MPH, MSc
  • PARP1-Targeted [18F]FTT PET/CT as an Imaging Biomarker to Select for PARPi Therapy in Patients with Metastatic Castrate-Resistant Prostate Cancer
    Principal Investigator: Neil Taunk, MD, MSCTS
  • Regulation of IFN-γ Signaling in BRCA1-Loss Dependent Breast Cancer
    Principal Investigator: Gather Thacker, PhD

 

External Grants: