Career Catalyst Grants from Susan G. Komen® Accelerate Breast Cancer Research

Two Washington University breast cancer researchers at Siteman Cancer Center have received national Career Catalyst Research Grants from Susan G. Komen® to accelerate their discoveries. Siteman is based at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis. The researchers are among 49 scientists in this round of funding receiving a total of $19.3 million in grants from the organization for research that advances precision medicine and/or helps to eliminate disparities in breast cancer outcomes.

Aimilia Gastounioti, PhD, Grant Recipient

Aimilia Gastounioti, PhD, Assistant Professor of Radiology at Washington University’s Mallinckrodt Institute of Radiology, received $445,716 to research “AI-based Methods on Medical Imaging to Predict Breast Cancer Risk in Black Women.” Priyanka Verma, PhD, Assistant Professor of Medicine in the Division of Oncology’s Section of Molecular Oncology, was awarded a three-year $450,000 grant to research “A New Chromatin-Directed Vulnerability in BRCA-Mutant Breast Cancers.”

Gastounioti is a principal investigator in the Computational Imaging Research Center (CIRC), an innovative technology collaboration between Washington University’s Schools of Medicine and Engineering. She will use computational image analytics and artificial intelligence (machine learning) to identify risk markers in mammograms of Black women. The research is the first-of-its kind study using computers to evaluate patterns seen in mammograms of Black women to better gauge their risk of developing breast cancer.

Gastounioti noted that while a woman’s risk is generally associated with imaging features of breast tissue, those features, or risk markers, have been primarily identified in mammograms from White women. “It’s not known if these same features can optimally predict breast cancer in Black women,” she said. “Significantly, Black women are affected by more aggressive cancers that show up at younger ages and they have a higher risk of dying from breast cancer. It is our hope that the outcomes of this project will have a major impact on mitigating racial disparities in breast cancer screening through advancements in personalized risk assessment for Black women.”

Gastounioti’s research team at Washington University includes Graham Colditz, MD, DrPH, an internationally recognized leader in breast cancer epidemiology and prevention; Debbie Bennett, MD, Chief of the Breast Imaging Section; Daniel Marcus, PhD, an expert in medical imaging informatics; Jingqin (Rosy) Luo, PhD, breast cancer statistician; and Ulugbek Kamilov, PhD, an expert in advanced machine learning algorithms. In addition, Gastounioti is partnering with Chantelle Nickson-Clark, founder of The Pink Angels Foundation in St. Louis, who will serve as the Patient Advocate Mentor for the study. Pink Angels is a non-profit foundation dedicated to providing encouragement and support to women diagnosed with breast cancer, particularly among Black women. Nickson-Clark, a breast cancer survivor herself, will serve as a liaison between researchers and the Black community and is an active leader in the development of educational materials and community engagement activities to help broaden the discussions on effective breast cancer risk assessments among Black women.

Priyanka Verma, PhD, Grant Recipient

Priyanka Verma, PhD, is extending her laboratory research into promising precision medicine pathways that could lead to better therapeutic targets to treat breast and ovarian cancers with mutations in the Breast CAncer (BRCA) genes. Cancers with these gene mutations are found in an estimated 70 percent of triple-negative breast cancers and in half of all high-grade serious ovarian cancers. Recently, Verma discovered that the depletion of a nucleosome sliding enzyme, Amplified in Liver Cancer 1 (ALC1), enhances sensitivity of poly polymerase inhibitors (PARPi) in BRCA-mutant breast and ovarian cancer cells. PARPi are inhibitors that block specific enzymes known to help cancer cells repair themselves. While this already is a therapy for BRCA-mutant breast cancers, severe side effects and growing resistance to PARPi limits its effectiveness.

“The emergence of PARPi resistance is inevitable,” said Verma. “Therefore, there is a pressing unmet clinical need for new therapies to treat these malignancies. We have early evidence in my lab that suggests that targeting the ATPase activity of ALC1 results in rapid destruction of BRCA-mutant breast cancer cells with no impact on normal cells.”

Research now is ongoing to determine the underlying mechanisms by which ALC1 inhibition achieves selective killing of BRCA-mutant breast cancer cells. “The Komen grant enables us to develop a robust platform for the design of ALC1 inhibitors and we can then validate our findings in mouse models. If results are similar, we can establish an innovative therapeutic approach for this high-risk group of women with BRCA-mutations who currently have limited treatment options.”