The Breast Cancer Research Foundation-AACR Career Development Award to Promote Diversity and Inclusion represents a focused effort to encourage and support investigators from diverse backgrounds that are underrepresented in the cancer-related sciences workforce and to foster their career advancement. 

2024 grantees

Research

Tumors can evade the immune system by intrinsically upregulating genes of immune evasion (e.g., CD47). However, it remains unknown whether mechanisms activating the immune evasion program in cancer cells are patient-specific. This information is key for generating tailored treatments to recruit the immune system for the eradication of cancer. Super-enhancers are long genomic regions that have potent gene regulatory activity and are critical for the upregulation of immune suppressive genes within breast cancer cells. This proposal aims to determine whether an eight-base pair binding motif, encoded by a patient-specific genomic insertion, actives a super-enhancer-driven program of immune evasion through the dual regulation of CD47 and the long intergenic non-coding regulatory gene 00636 (LINC00636). Therefore, this insertion could be a signature of tumor immune escape and, consequently, progression in patients carrying this genomic variant.

Biography

Dr. Betancur received her bachelor’s degree in biology from Stony Brook University, NY, and her doctorate in cell biology from California Institute of Technology. She completed her postdoctoral training at Stanford University, where she studied the genomic mechanisms that activate an immune evasion program in cancer cells through CD47 upregulation. Dr. Betancur became a faculty member at the University of California, San Francisco in 2019, where her research focuses on gene regulation and immunogenomics.

Acknowledgment of Support

“The Breast Cancer Research Foundation-AACR Career Development Award to Promote Diversity and Inclusion enables me to engage in programs that promote diversity and inclusion while performing cancer research. This preserves my passion for both causes and ensures I can contribute to them with dedication.”

Research

Dr. Sanchez-Vega’s team will create and analyze a comprehensive multimodal database for a racially diverse population of 1,600 locally advanced breast cancer patients treated with neoadjuvant chemotherapy. This database will include comprehensive clinical information, as well as digitized pathology slides, magnetic resonance images, and targeted DNA sequencing data. This cohort will be used to build race-informed multimodal machine learning algorithms that predict complete pathological response to neoadjuvant therapy. Dr. Sanchez-Vega will investigate the predictive performance of individual data modalities when patients are stratified by race and relevant molecular subtypes. His team will design deep learning models that integrate multiple data modalities in a race-informed manner and optimize them to generalize to diverse real-world populations. The database and computational pipelines generated will be made publicly available to facilitate long term development of multimodal methods that further improve predictive and prognostic capabilities for breast cancer patients.

Biography

Dr. Sanchez-Vega earned his doctorate in applied mathematics and statistics, with an area of specialization in computational medicine, from Johns Hopkins University. He is currently an assistant attending in the computational oncology service of the Department of Epidemiology and Biostatistics at Memorial Sloan Kettering. Dr. Sanchez-Vega’s research focuses on translational applications of machine learning, statistical modeling, and computational methods to the field of cancer genomics and precision oncology. His group is also interested in the use and implementation of novel computational approaches for multimodal integration of genomic sequencing data and orthogonal sources of biological and clinical information.

Acknowledgment of Support

“The Breast Cancer Research Foundation-AACR Career Development Award to Promote Diversity and Inclusion will provide me with dedicated resources and protected research time to work on breast cancer disparities research. Importantly, the analysis methodology and the race-informed computational models that my team will develop will be extendable to investigate related questions in other cancer types in the future.”

2023 grantees

Research

Social determinants of health (SDOH) may worsen cancer disparities. The Penn Individualized Management for Patient-Centered Targets (IMPaCT) model is a standardized community health worker intervention for addressing health inequity and SDOH, with proven effectiveness in chronic disease management. The IMPaCT program has currently been scaled up to 50 organizations in 20 states and the Veterans Administration health system, but the effectiveness of this model has not been previously studied in patients with cancer. The goal of this proposal is to evaluate the effectiveness of IMPaCT on cancer stage distribution, missed oncology clinic appointment rates and cancer-related outcomes in patients previously enrolled in IMPaCT across the University of Pennsylvania Health System from 2013-2022, who received any cancer diagnosis following enrollment in IMPaCT. Additionally, Dr. Martei and her research group plan to pilot and evaluate implementation outcomes of a breast cancer-adapted community health worker program integrated into breast cancer care delivery, using the Implementation Mapping for Adaptation framework. 

Biography

Dr. Martei graduated from Harvard College and Yale School of Medicine. She completed her internal medicine training at the University of California, San Francisco, and hematology-oncology fellowship and Master of Science in clinical epidemiology at University of Pennsylvania. Dr.  Martei is currently a medical oncologist, an assistant professor of medicine, and the vice chief of diversity, inclusion and health equity in the Hematology-Oncology Division at the University of Pennsylvania. Her research is focused on implementation strategies for eliminating global disparities in breast cancer outcomes by optimizing high quality breast cancer therapy delivery in low-resource settings and among patients with complex co-morbidities.

Acknowledgement of Support

“This research focus aligns with my vision for health equity in cancer, and I am excited for the opportunity to be able to implement this proposal through this Breast Cancer Research Foundation-AACR Career Development Awards to Promote Diversity and Inclusion mechanism. This funding is critical for building preliminary data in an area of disparity and great need.” 

Research

Patients with breast cancer are thought to be intrinsically resistant to immune checkpoint inhibitors, in part, due to a suppressed tumor microenvironment (TME) by myeloid derived suppressor cells (MDSCs). Previous work by the Roussos Torres lab demonstrated in preclinical models that entinostat decreases MDSC suppression. A better understanding of mechanisms to overcome the immunosuppressive TME of breast cancer will provide a basis for more specific molecular and/or cellular targets. Dr. Roussos Torres will examine the molecular and cellular mechanisms regulating intra- and inter-tumoral MDSC response to entinostat as well as the contribution of entinostat-treated macrophages and dendritic cells on decreased MDSC suppressive function. These findings will be validated in samples collected from patients enrolled in a clinical trial (NCI-9844).

Biography

Dr. Roussos Torres received undergraduate degrees in microbiology, immunology and molecular genetics and dance, from the University of California at Los Angeles in 2005. She then received her medical and doctorate degrees (MD/PhD) from the Albert Einstein College of Medicine in 2012. She completed her internal medicine residency at the Hospital of the University of Pennsylvania in 2014, and a fellowship in oncology in 2018 at Johns Hopkins University. Dr. Roussos Torres became an assistant professor at Johns Hopkins University. She is currently an assistant professor at the University of Southern California in the Division of Oncology.

Acknowledgement of Support

“As a passionate female physician scientist in the throes of building my career, I am honored to receive this award from BCRF and AACR! This type of national recognition and support is invaluable and a tremendous honor as I continue to strive for excellence in all that I do.”

2022 Grantees

Research

Dysregulated immunoglobulin production and preexisting autoantibodies may contribute to autoimmune adverse events (AE) of immunotherapy (e.g., thyroid disease) and immune-mediated AEs of chemotherapy (e.g., peripheral neuropathy (CIPN)). This proposal aims to identify autoantibodies that are associated with therapy-induced immune-related AEs (irAEs) in patients with breast cancer. Dr. Blenman is set to: 1) determine if preexisting serum autoantibodies are associated with irAEs, and 2) determine if specific preexisting serum autoantibodies protein epitopes are associated with irAEs. This study has the potential to uncover biomarkers that can be used to forecast and monitor irAEs before, during, and after therapy to help guide treatments and evaluate survivorship.

Biography

Dr. Kim Blenman is an immunologist and clinical chemist who uses and develops novel software tools to understand the mechanisms responsible for disparities in disease pathogenesis and therapeutic response. In addition to an undergraduate degree in chemistry and a doctoral degree in immunology, she has a certificate in Drug Development and Regulatory Sciences from the University of California, San Francisco. She had the privilege of learning and working on drug discovery and clinical development at Procter & Gamble’s Pharmaceutical division as a senior scientist and as a global research director for autoimmune diseases, inflammatory bowel disease, and irritable bowel syndrome. She was also a Postdoctoral Fellow at the City of Hope Comprehensive Cancer Center in Duarte, California. Dr. Blenman is currently an Assistant Professor in the Yale School of Medicine Department of Internal Medicine Section of Medical Oncology and the Yale Cancer Center as well as in the Yale School of Engineering and Applied Science Department of Computer Science.

Acknowledgment of Support

The Breast Cancer Research Foundation-AACR Career Development Awards to Promote Diversity and Inclusion will be instrumental in helping me be a leader in the field and an advocate for equity in clinical research for all.

Research

Although lymph nodes play a critical role in the expansion of anti-cancer T cells, they are frequent sites of metastatic spread. Prior work by Dr. Jones and colleagues found that compression of blood vessels by breast tumors in lymph nodes is associated with impaired T cell entry into these metastatic tumors. In this project, Dr. Jones and his group will test the hypothesis that relieving this compression will improve T cell entry into nodal metastases. They will use long-term intravital imaging to measure whether decompressing blood vessels enhances T cell entry into metastatic tumors. Further, they aim to combine decompression therapy with immune therapy to test whether this drug combination will enhance the killing ability of T cells that enter lymph node tumors.

Biography

Dr. Jones obtained his PhD in Immunobiology from Yale University, where he studied basic mechanisms of lymphatic vessel expansion during pathological inflammation. He completed his postdoctoral training at Massachusetts General Hospital/Harvard Medical School, where he developed mouse models of lymphatic metastasis and characterized tumor progression in lymph nodes. He is currently an assistant professor at the Boston University School of Medicine in the Department of Pathology and Laboratory Medicine. His lab studies immune suppressive mechanisms within metastatic tumors with the goal of identifying novel targetable proteins for effective therapy of advanced breast cancer.

Acknowledgment of Support

I appreciate the Breast Cancer Research Foundation’s and the AACR’s commitment to supporting underrepresented minority investigators and I am honored to receive the 2022 Career Development Award to Promote Diversity and Inclusion. This support will be instrumental in allowing us to understand and overcome mechanisms of tumor-mediated T cell suppression.

2021 grantee

Research
Breast cancer stem cells can emerge as a result of MYC-induced reprogramming of committed cell types (such as luminal epithelial cells in the mammary duct). Emerging evidence points to the role of super-enhancers in this reprogramming. The transcriptional coactivator Mediator links super-enhancers to target promoters within large transcription hubs and promotes MYC activity at super-enhancers, suggesting that Mediator facilitates reprogramming. Dr. Saldivar has uncovered an unexpected link between large transcription hubs and ATR, a replication stress-response kinase that is needed for MYC-driven cancers. His group will use a combination of time-lapse confocal imaging and single-cell sequencing to uncover a potential oncogenic role of ATR signaling within these hubs during MYC-induced reprogramming and breast cancer stem cell emergence.

Biography
Dr. Saldivar received his PhD at Ohio State University, where he studied the origins of genomic instability in premalignant cells. He completed his postdoctoral work at Stanford University, where he uncovered a cell cycle checkpoint pathway controlling the S to G2 transition. He is currently an assistant professor in the Division of Oncological Sciences and a member of the Cancer Early Detection Advanced Research Center at Oregon Health & Science University. His lab studies the mechanisms driving reprogramming in the early stages of cancer.

Acknowledgment of Support
I am deeply honored to be selected as a recipient of the 2021 Breast Cancer Research Foundation-AACR Career Development Award to Promote Diversity and Inclusion. As an early career investigator, this award will enable me to conduct research focused on the mechanisms of oncogenic reprogramming in breast cancer.