Catherine Peachey Breast Cancer Research Grant

This research program is built on the shared interests and goals between the WGHI and the Catherine Peachey Fund to promote advances in breast cancer research and treatment and to support research that is best positioned to move from the bench to clinic. The Catherine Peachey Fund was established in memory of Cathy Peachey, one of the founders of the Indiana Breast Cancer Coalition. 

Announcement: Dec, 2024

Due:                   TBA

 

Awarded Proposals

2024

W. Andy Tao, PhD

Professor 
Chemical Biology and Analytical Chemistry

Project title: “Monitoring High-risk Populations for Breast Cancer through Measuring Functional Proteins from Plasma-derived Extracellular Vesicles"

Focusing on innovative breast cancer early detection, this project proposes to establish a novel strategy by quantitatively measuring functional proteins in extracellular vesicles (EVs) as effective biomarkers for early onset of BRCA-associated breast cancer by analyzing plasma samples from BRCA patients with or without breast cancer. Exosomes and other EVs have emerged as promising sources for discovering tumor-relevant biomarkers from biofluids such as blood. Our recent study revealed for the first time that a large number of phosphoproteins in EVs could be extracted from a small volume of plasma, identified by high-resolution mass spectrometry, and verified as potential breast cancer markers. We hypothesize that proteins with post-translational modifications (PTMs) in EVs are novel cancer biomarkers and can be developed to detect the early onset of BRCA1- and BRCA2-associated hereditary breast cancer. Through this application, we will implement a novel technique for EV isolation suitable for clinical applications, rigorously characterize cancer-relevant EV isolation efficiency and specificity, and then focus on the identification and validation of EV PTM proteins through machine learning for early onset of breast cancer in BRCA patients. 

Matthew Scarpelli, PhD

Assistant Professor 
School of Health Sciences

Project title: “Improving Breast Cancer Radiotherapy by Theragnostic Targeting of Tumor-Supporting Macrophages"

Radiotherapy is an indispensable part of care for breast cancer patients; however, radiotherapy is not effective for all patients and does include adverse side effects, lowering quality of life. Prior observations suggest radiotherapy outcomes are improved by combining both radiotherapy and therapies targeting tumor associated macrophages (TAMs). However, lack of an established mechanism by which TAM-targeted therapies augments radiotherapy has posed a barrier to clinical translation. Thus, there is an urgent need to establish mechanisms by which TAM-targeted therapy alters radiotherapy. The main objective of this project is to determine the cytotoxic mechanisms and anti-tumor efficacy of integrating TAM targeting within radiotherapy regimens for breast cancer. For these studies, therapeutic targeting of TAMs will be accomplished by repurposing the promising TAM-targeted agent ferumoxytol. Ferumoxytol is an FDA-approved iron nanoparticle that has been previously used to non-invasively assess breast cancer TAMs with magnetic resonance imaging (MRI). The main hypothesis is that ferumoxytol will reduce immunosuppressive, tumor-promoting TAMs. This reduction in TAMs is expected to increase breast cancer sensitivity to radiotherapy by both disrupting TAM-cancer cell heterotypic survival signaling and increasing radiation-induced anti-tumor immune responses. Upon completion, this project will have established the efficacy and cytotoxic mechanisms of combining TAM-targeted therapy with radiotherapy. This contribution is expected to be significant because it will provide knowledge regarding the role of TAMs in modulating breast cancer resistance to radiotherapy; and it will lead to the development of more effective radiotherapeutic strategies. 

2023 

Ann Kirchmaier, PhD

Associate Professor 
Department of Biochemistry

Co-PI:

Nadia Atallah Lanman, PhD
Research Associate Professor
Department of Comparative Pathobiology

Project title: “Revealing Genome Integrity Defect Targets in Breast Cancer"

The long-term goals of the project are to understand how errors during DNA replication and repair contribute to breast cancer formation and progression, and to develop high-impact "precision medicine "strategies and novel biomarkers for predicting or assessing responsiveness to chemotherapeutic drugs based on cancer-specific defects during DNA replication. We hypothesize breast cancers contain tumor-specific genetic or epigenetic defects that will cause a "molecular signature" of preferential stalling/collapse of replication forks at distinct types of impediments. We further hypothesize that when the preferred fork restart pathway is defective in breast cancer, an alternate pathway will become critical. However, if the alternate pathway is inhibited with chemotherapeutics, we predict a  "negative synthetic interaction" will occur between the genetic defect in breast cancer and the inactivated drug target, resulting in catastrophic DNA damage that will disrupt growth and viability. In this proposed proof-of-concept work, we will evaluate a patient-derived breast cancer line with a known genotype to 1) identify the sites of and types of replication fork impediments genome-wide, 2) determine which drugs this breast cancer line is sensitive to, and identify breast cancers with related sensitivities and genetic defects computationally, plus 3) demonstrate how chemotherapeutics influence replication through impediments and growth for the original breast cancer line plus a second breast cancer line predicted to respond similarly. 

Dorothy Teegarden, PhD

Professor 
Department of Nutrition Science

Co-PIs:
Kimberly Buhman, PhD
Professor
Department of Nutrition Science

Chaylen Andolino, PhD
Senior Proteomics Research Scientist
Bindley Bioscience Center

Project title: “Role of the Proteome of Cytoplasmic Lipid Droplets in Metastasis"

Increased cellular storage of fatty acids (FAs) in cytoplasmic lipid droplets (CLDs) is associated with increased breast cancer aggressiveness and poorer patient outcomes, suggesting that CLDs contribute to metastasis. However, how CLDs contribute to metastasis is not known. To begin our investigations, from our preliminary analyses, we have identified two pathways (ferroptosis and cell-cell adhesion) where proteins are differentially located in the CLD-associated fractions in less metastatic compared to metastatic cell lines. In these proposed studies, we will 1) complete additional proteomic analyses of CLDs from cell lines with altered metastatic capability, 2) validate the association of selected proteins with CLDs whose presence in the CLD fraction is associated with metastatic capacity, and 3) preliminarily test the role of the specific proteins or pathways in steps required for metastasis. It is critical to narrow down the selection of proteins so that future studies can be designed to target specific pathways or proteins associated with CLDs to identify how their association with the CLDs promotes metastasis, thereby allowing for the future development of targeted strategies to prevent or treat metastases.

2022

Joseph Rispoli, PhD

Assistant Professor 
Department of Biomedical Engineering

Project title: “Early Breast Cancer Evaluation in High-Risk Subjects using Advanced MRI Modalities"

Early detection and diagnosis of breast cancer are critical for effective treatment and increased survival rate. Developing a highly precise, sensitive, and rapid early-stage breast cancer diagnostic tool is imperative in the medical imaging field as currently available methods such as mammography, ultrasound, computerized tomography, or biopsy are neither sensitive enough, nor suitable for young women. Breast magnetic resonance imaging (MRI) has gradually become more available as a diagnostic tool for evaluation of treatment response, preoperative staging, tissue perfusion, and biopsy guidance. The aim of this study is to develop a comprehensive imaging protocol using both an in-house and a commercially available flexible coil to investigate the sensitivity and specificity of advanced MRI methods for early breast cancer detection in high-risk subjects with dense breast tissue or family history of breast cancer. 

Michael Wendt, PhD

Associate Professor 
Department of Medicinal Chemistry and Molecular Pharmacology

Project title: “Targeting FGFR to prevent obesity-induced metastatic recurrence in breast cancer"

Breast cancer is still amongst the deadliest cancers for women due to the high late-recurrence and high metastasis rates. Preclinical studies have revealed that obesity is a major contributing factor to tumor relapse and distant organ metastases occurring 5-10 years after treatment. Fibroblast growth factor receptor (FGFR) signaling is suggested as a promoting factor in obesity-induced breast cancer recurrences. However, due to lack of clinically relevant in vivo models, it is still not clear how obesity activates dormant disseminated tumor cells and promotes distant organ metastasis. In this study, we will utilize our newly developed mouse model to study the role of FGFR signaling in obesity-mediated breakage of the tumor dormancy and metastatic outgrowth.

2021

Luis Solorio, PhD

Assistant Professor 
Department of Biomedical Engineering

Project title: “Evaluating the impact of complex extracellular matrix proteins using a high-throughput magnetically actuated 3D microtumor environment for more precise breast cancer drug screening.”    

Metastasis is the single greatest driver of cancer related mortalities. Once metastasized, breast cancer patient survival rate drops almost 75%. A defining hallmark of metastasis is the ability for tumor cells to modulate the microenvironment to facilitate invasion and colonization. After tumor cells have invaded into a new tissue, the mechanical actuation of the metastatic site plays a key role in determining if the cell enters a growth cycle or dormancy. Therefore, there is a critical need to determine how the physical attributes of the microenvironment at the metastatic location dictates the tumor cell fate. This project uses an innovative and unique approach of a 3D test platform to evaluate the effect of the mechanical properties of extracellular environment on metastatic breast cancer growth and drug responsiveness.  

Michael Wendt, PhD

Associate Professor 
Department of Medicinal Chemistry and Molecular Pharmacology

Project title: “Understanding the role of obesity in facilitating resistance to HER2- targeted therapies.”    

Obesity is a significant risk factor for breast cancer recurrence and metastatic progression especially for postmenopausal women. Almost 30% of breast cancer eventually relapse and metastasize to distant organs after being treated with a multi-modal therapies. Metabolic reprograming and acquired resistance to current therapies have been considered as two important underlying factors behind high recurrence and targeted therapy resistance rates in metastatic breast cancers, but neither of these molecular mechanisms are fully elucidated. This project will investigate how obesity-driven metastasis regulates lipid metabolism, leading to an acquired resistance to breast cancer treatment, and how to overcome such drug resistance.