Our research team is investigating a small RNA molecule in breast cancer cells. Despite progress in targeting fast-growing tumor cells with chemotherapy, breast cancer cells can develop resistance, spreading to other organs and jeopardizing patient survival. Our study discovered a small RNA molecule that can promote faster cancer cell growth while inhibiting their ability to spread. This suggests a potential role for this small RNA in enhancing chemotherapy, particularly for triple-negative breast cancer (TNBC), by encouraging TNBC cells to stay localized and responsive to treatment. Our goal is to further understand the mechanisms of this small RNA function and utilize it to restrain TNBC cells, making them more receptive to chemotherapy. 

Macrophages are normal cells in the body that when in tumors (tumor-associated macrophages, TAMs) they help drive tumor growth. We have found that the protein PU.1 controls TAM function, both as part of 1) the colony-stimulating factor 1 (CSF1) receptor/PU.1 signaling pathway and 2) PU.1’s regulation of genes by its interaction with highly active areas of the genetic sequence called superenhancers. In this award, we will target both of these ways PU.1 regulates TAM function using small molecule inhibitors and microparticle-mediated drug delivery systems in mouse models of primary breast cancer tumors across subtypes.

Triple negative breast cancer (TNBC) is an aggressive type of breast cancer that does not respond to current treatment options for breast cancer. This is because TNBC lacks the receptors targeted by current therapies in other breast cancers. Focal adhesion kinase (FAK) is a protein kinase that promotes tumor growth and metastasis in many cancers, and small molecule FAK inhibitors are being tested in clinical trials. Interestingly, we found that FAK inhibition increases some estrogen receptor (ER) signaling pathways in TNBC cells, but not in other breast cancer subtypes. FAK inhibitor in combination with an activator of a specific ER signaling pathway in TNBC cells showed a synergic effect by reducing cell proliferation, and showed a larger reduction in tumor mass and lung metastasis compared to single treatment groups in TNBC mouse models. We think FAK inhibition elevates some ER signaling pathways be reducing EZH2, a protein associated with gene silencing. To test this idea, we will investigate FAK inhibitor and ER activation in different cell lines, mouse models, and samples obtained from TNBC patients. This study aims to understand how FAK affects estrogen signaling to find better ways to treat TNBC patients through the use of FAK inhibitors in combination with ER activators. 

Black women with breast cancer are at an increased risk of heart problems like high blood pressure, stroke, and premature death. The ECHO: Exploring Cardiovascular Health Outcomes in Black Breast Cancer Survivors study will provide insight on Black breast cancer survivor’s perceptions of heart health and health behaviors. With a community advisory board, we will work to co-create an intervention that can educate and support Black breast cancer survivors to achieve greater heart health.

Angiogenesis or the growth of new blood vessels within cancers supplies oxygen and nutrients and disposes wastes. Once new blood vessels grow into the tumor mass, both blood vessels and tumor cells grow crazy and spread to other organs. This study will introduce a new concept that arteriolar angiogenesis functions as tumor vascular microenvironment to promote formation of metastatic cancer stem cells. We will test novel vascular signaling-targeting strategies to control the spread of these malignant cells to other organs. 

Triple negative breast cancer is aggressive with a low survival rate after the disease spreads. Our studies will focus on how mechanical forces drive cancer cell growth, movement, and response to drugs. Results will help develop novel treatment strategies to block mechanical regulation of tumor growth. 

The change in paradigm from a cancer cell-centric approach to a tumor-supporting, non-cancer cell-centric approach in treating cancers has revolutionized cancer treatment in recent times and improved the patient’s quality of life in several ways. Breast cancer (BC) is a complex disease that is often identified with the presence of hardened mass or tissue. It results from an overabundance of non-cellular components called extracellular matrix (ECM), primarily collagen, fibronectin, and matrix cross-linkers, and predicts poorer disease and therapeutic outcomes in patients. The ECM imparts a gradual elastic force to the cancer cells, known as matrix stiffness, which alters the cancer cell biology and promotes metastatic progression. Manipulation of cancer tissue stiffness is envisioned as a major strategy for improvement in cancer therapeutics. The current study will identify the role of lysine-deficient kinase 1(WNK1), which is abundantly expressed in cancer-associated fibroblasts (CAFs), the most prominent non–cancer cell population in BC TME and the primary depositor of ECM, on matrix stiffness in BC.

Women diagnosed with breast cancer live with the unfortunate fear of disease relapse and spread. Reliable follow-ups, monitoring, and guided treatment are essential for longer survival and healthy living of these women. The available methods for the early and accurate detection of recurrent and metastatic lesions need significant improvement to offer better survival. We are developing a new blood-based mitochondrial DNA detection kit, which may identify aggressive tumors early, thereby aiding in better and longer life for these women. 

Breast cancers are composed of both cancerous and non-cancerous cells. Recent research highlighted the importance of non-cancerous cells, especially neurons, which are associated with poorer outcomes. This project focuses on understanding and treating “innervated“ breast cancers, by targeting both the cancerous cells and the neurons. The goal of the project is to develop innovative treatment approaches and clinical trials that consider the presence of nerve cells in breast cancer.

Obesity, which is a widespread problem in the US, has been linked with increased incidence, disease recurrence and worse prognosis in breast cancer as 70% of breast cancer patients in the US are at an increased risk for cancer recurrence and death due to obesity. The interactions between fat cells with cancer cells and other cells in the tumor microenvironment facilitate the survival of cancer cells and aid in disease progression. Lymphatic endothelial cells that form the lymphatic vessels are an essential part of the tumor microenvironment. As obesity promotes metastasis and excess fat is reported to promote lymphatic dysfunction, which in turn plays a major role in regulating the tumor microenvironment, our hypothesis is that the crosstalk between adipocytes and lymphatic endothelial cells play a pivotal role in breast cancer metastasis. In this regard, the goal of the study is to decipher the role of neurotensin, a 13 amino acid neuropeptide that is highly expressed in breast cancer particularly by the lymphatic endothelial cells, and favors cancer progression, in regulating the interactions between adipocytes and lymphatic endothelial cells.  

Landscape phage “substitute antibodies”, invented by Petrenko and Snith, are promising biosensing probes for  detection of cancer cell-derived biomarkers. The goal of this proposal is the development and validation of robust inexpensive highly sensitive and easily available phage-based analytical tools for diagnosis, prognosis, and monitoring of cancer diseases using blood testing, or “liquid biopsy”. Considering the reliability and robustness of landscape phage interfaces in major analytical platforms, and scalability of phage production, we envision a principal breakthrough in  public health security through introducing selective, and economical analytical toolkits for massive breast cancer control.  

Breast cancer is the most diagnosed cancer among women, with wide inter-patient variability in response to treatment and eventual resistance to standard chemotherapy drugs. We have designed a novel computational algorithm called “secDrug” that predicts potential secondary drug candidates against drug-resistant breast cancer. In the proposed study, titled ‘A novel strategy to prevent the development of drug resistance in Breast Cancer’, our team comprising of health innovation scientists and translational researchers from Auburn University and the University of Illinois, Urbana-Champaign, plans to combine in silico modeling with single-cell -omics studies and mouse xenograft models to validate the predicted secDrugs as novel agents for treating drug-resistant breast cancer, and to identify sub-cellular pathways underlying drug resistance and the mechanism of action of the top secDrugs. We are confident that the successful completion of our work will attract high-level funding from national research institutes to cure the lethal subtypes of breast cancer. 

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that is difficult to treat. This study explores a new treatment approach that combines two innovative therapies — one that enhances the immune system’s attack on cancer and another that reprograms immune cells within the tumor to fight cancer cells. By testing this combination in a mouse model that mimics human TNBC, we aim to develop a more effective and safe treatment for patients with this difficult-to-treat disease.

The study focuses on improving breast cancer treatment for African-American women by exploring their unique genetic traits. African-American women often face more aggressive breast cancer types, which are harder to treat due to limited targeted therapy. However, most research has been focused on women of European ancestry, which leaves a gap in understanding how genetics might influence treatment in African-American women. Therefore, by analyzing breast cancer tissue samples from African-American women, we aim to identify the genetic patterns related to breast cancer which will further be compared with the existing treatments approved by FDA to determine which therapies are most likely to work for these patients. This could lead to personalized treatment plans, improving outcomes and addressing health disparities in breast cancer care for African-American women. 

Breast cancer (BCa) is a major health concern, especially because it is often diagnosed late when treatment options are less effective. Early detection is crucial for improving treatment outcomes and reducing healthcare costs. While many methods for diagnosing BCa exist, they often have drawbacks, like being invasive, expensive, or requiring skilled personnel. This study proposes a new, non-invasive method for detecting breast cancer early using a biomarker called 8-oxo-dG, which is found in higher levels in the urine and blood of people with BCa. The goal is to develop a simple, quick, and affordable device that can detect this biomarker in urine samples, offering an easy way to monitor and diagnose BCa early.

Macrophages are one of the important types of white blood cells that protect us from various infections. Tumor cells, on the other hand, constantly recruit and use them to promote tumor growth, metastasis, treatment resistance, and immune evasion. Triple negative breast cancer (TNBC), in particular, is characterized by an excessive accumulation of tumor promoting tumor associated macrophages (TAMs). Several drug molecules that act on TAMs are now being investigated for TNBC treatment, however they are frequently associated with undesirable toxicities. The goal of this proposal is to develop a novel drug candidate that selectively re-educates tumor-supporting TAMs, converts them into tumor killing macrophages, and limits TNBC tumor growth. 

Breast cancer brain metastases usually develop late after diagnosis and treatment of primary breast cancer. Throughout this duration, metastatic breast cancer cells can remain in an undetectable dormant (sleep-like) state finally to wake up and cause brain metastases. Our goal is to study the role of immune cells in the process of reawakening dormant metastatic breast cancer cells using brain tissue mimetic environments. If successful, these studies would provide a foundation for the development of novel investigational interventions against the incurable breast cancer brain metastases.  

DNA variants in the genes BRCA1 and BRCA2 are the best predictors for an individual’s risk for breast cancer. Despite these established connections, predicting an individual’s risk can still be challenging. This study will use new genetic technologies to explore the function of variants occurring near known cancer risk genes to identify new regions with the potential to alter breast cancer risk. The ultimate goal is to create a more complete catalog of variants impacting cancer risk and facilitate development of tests that could improve preventative care and personalized screening to prevent and treat cancer in high-risk individuals.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that is difficult to treat. This study explores a new treatment approach that combines two innovative therapies — one that enhances the immune system’s attack on cancer and another that reprograms immune cells within the tumor to fight cancer cells. By testing this combination in a mouse model that mimics human TNBC, we aim to develop a more effective and safe treatment for patients with this difficult-to-treat disease.