Dr. Perry is investigating how a key immune cell in the tumor microenvironment, the macrophage, contributes to cancer’s development and progression. His work focuses on triple-negative breast cancer, as it remains one of the deadliest cancers, especially to young women and Black women, with decades of treatment efforts failing to improve patient outcomes. Specifically, Dr. Perry aims to combine novel methods of manipulating and imaging the cellular metabolism to better understand how macrophages contribute nutrients to help cancer cells meet their nutrient demand and escape treatment. This work will not only provide a method for diagnostic biomarker identification but also establish a novel platform for developing individualized treatments. Importantly, his work has the potential of being broadly applicable to all difficult-to-treat metastatic adenocarcinomas.

Most cancers develop in the epithelial tissue, which includes the skin and internal organ linings.  Hemidesmosomes (HDs) are adhesive structures that anchor epithelial cells to the underlying base layer and maintain tissue integrity. While HD disassembly occurs normally during wound healing, tumor cells can exploit this process to detach and spread to other parts of the body. Dr. Bagde is studying how HD components interlock like Lego blocks to form stable HDs in healthy tissues and how they disassemble in cancerous tissues. To investigate this phenomenon, Dr. Bagde plans to develop organoids—self-organizing mini-organs grown in a petri dish to study disease progression. By creating simple base layers that simulate the supportive properties of the native organ base layer, he plans to promote the growth of both normal and cancerous organoids. This work has the potential to support the development of personalized cancer therapies based on patient-derived tumor samples. Dr. Bagde received his PhD from Cornell University, Ithaca and his MS and BS from the Indian Institute of Science Education and Research, Pune.

Dr. Cote is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr. Cote is combining tissue-specific genetic manipulations and laser cell ablations with live imaging during Caenorhabditis elegans digestive tract development to reveal how intracellular organization in one cell type can influence the alignment, polarity, and function of cells in the neighboring tissues.

The cellular response to DNA damage is coordinated by an enzyme known as ATM kinase. Mutations in ATM are found in approximately 1% of the population and contribute to an increased risk of both hereditary and sporadic cancers, including breast cancer. Dr. Kim’s research investigates how ATM suppresses the production of double-stranded RNAs (dsRNAs) in response to DNA damage. These dsRNAs play a critical role in tumor progression. Dr. Kim aims to identify the key molecular players involved in ATM-mediated suppression of dsRNAs and elucidate how the loss of ATM function triggers inflammatory responses through dsRNA sensing pathways. By uncovering these mechanisms, Dr. Kim aims to deepen our understanding of how ATM mutations drive cancer development and uncover novel therapeutic strategies for ATM-associated cancers. Dr. Kim received his PhD and BS from the Ulsan National Institute of Science and Technology, Ulsan.

Human cells compact their vast genomes into the small confines of the nucleus by wrapping their DNA into a highly complex structure called chromatin. Packaging DNA into chromatin, however, affects all nucleic acid-transacting machines (e.g., transcription factors) that need to access the genomic information stored in the DNA. NuRD is a large multi-subunit protein complex that plays a major role in making chromatin either accessible or inaccessible. Dysregulation of NuRD and aberrant targeting of the complex can result in the emergence of several types of cancers, including breast, liver, lung, blood, and prostate cancers. Dr. Osorio Valeriano’s [Philip O'Bryan Montgomery, Jr., MD, Fellow] work will reveal mechanistic aspects of NuRD-mediated chromatin regulation and pave the way for the development of novel therapeutic approaches that target cancers more effectively. Dr. Osorio Valeriano received his PhD from Philipps University and his MSc and BSc from the National Autonomous University of Mexico.

One way cancer cells evade immune attack is by constructing a thin material barrier called the glycocalyx on their surface to evade detection and destruction by surveilling immune cells. Tiny changes in the glycocalyx thickness, as small as 10 nanometers, can affect the anti-tumor activity of immune cells, including CAR T cells. Dr. Park’s [Merck Fellow] goal is to develop strategies to endow CAR T cells with the ability to penetrate the glycocalyx barrier in solid tumors such as breast cancer and glioblastoma. These strategies will increase the effectiveness of CAR-T cell therapy against solid tumors by overcoming a significant mechanism of immune cell evasion. Dr. Park received his PhD from Cornell University, Ithaca and his BS from Korea Advanced Institute of Science and Technology, Daejeon.

Groundbreaking advances in immunotherapy have revolutionized the treatment of cancer. In particular, new antibody drugs that block immunosuppressive pathways have achieved remarkable success in reawakening the immune system to clear tumor cells, leading to lasting cures in patients whose cancers do not respond to any other therapies. Unfortunately, the majority of patients (>70%) do not respond to immunotherapy treatment. It is difficult to predict which patients will benefit, creating an urgent demand for novel immunotherapy drugs that act through alternative mechanisms. Dr. Spangler is working to develop a class of antibody therapeutics that target cancer-promoting pathways in a different way than all current immunotherapies, with the goal of drastically expanding the percentage of cancer patients who benefit from them.

Breast cancer is the most frequent cancer in women and the second-leading cause of cancer deaths in women worldwide. Triple-negative breast cancer is among the most aggressive subtypes; its name refers to the fact that it lacks all three primary markers of breast cancer, making it particularly challenging to detect and treat. Although our ability to detect early-stage breast cancer has improved substantially over the past few decades, anticipating whether and how fast a tumor will progress to metastatic disease remains challenging. Dr. Trenado-Yuste aims to improve our ability to predict a tumor's disease course and response to therapy by creating a new framework of biomathematical models and experimentally engineered tumors, which may aid in prognostication and decrease cancer-related deaths.

Experimental research in cancer biology also drives a need for new computational models. This project focuses on mathematical modeling, with an emphasis on developing agent-based and pharmacokinetic models, to help clarify how tumor spheroids progress and respond to drug treatments. The importance and innovation of the proposed theoretical and computational methods lie in their potential to identify the optimal combinations of personalized treatment schedules for individual patients.

Many immunotherapy strategies require patient T cells to recognize specific cancer-associated antigens. However, it is unclear what these antigens are and how they contribute to tumor shrinkage during treatment. Dr. Zhu [HHMI Fellow] will use large-scale antigen screening methods to identify cancer-associated antigens recognized by T cells that are activated in breast cancer patients during immunotherapy treatment. Mapping the antigen landscape of breast cancer will identify targetable antigens and improve future immunotherapies. Dr. Zhu received his PhD from The Rockefeller University and his BSc from the National University of Singapore.