Breast Cancer

Current Projects
Lauren E. Cote, PhD

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.

Project title: "Constructing one continuous digestive tract, cell by cell"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Jessica L. Feldman, PhD
Cancer Type: Gastric, Other Cancer, Breast, Colorectal, All Cancers
Research Area: Developmental Biology
Luisa F. Escobar-Hoyos, PhD

Current pancreatic cancer chemotherapies are not effective, and targeted therapies are only applicable in about 5% of cases. Furthermore, pancreatic cancers cause immune cell stress, limiting the success of immunotherapies in this disease. Using animal models and tumor samples from pancreatic cancer patients, Dr. Escobar-Hoyos has discovered that changes in RNA splicing, a process that controls protein diversity in cells, are crucial for pancreatic cancer development, therapy resistance, and disruption of anti-tumor immunity. The proposed project will dissect the molecular role of RNA splicing in pancreatic cancer, which likely drives the disease's lethality. She seeks to develop a novel anti-RNA splicing therapy with dual action-a targeted therapy against tumor cells coupled with an immunotherapy to restore immune cell anti-tumor activity-to more effectively treat pancreatic cancer patients.

Project title: "Understanding RNA splicing in tumor-cell adaptation and anti-tumor immunity"
Institution: Yale University
Award Program: Innovator
Cancer Type: Breast, Lung, Pancreatic
Research Area: Cell Biology
Siting Gan, PhD

Dr. Gan focuses on brain metastasis in lung and breast cancer, a major cause of death for these patients. She is applying the latest single-cell technologies and developing computational tools to dissect how tumor cells interact with resident brain cells to mediate the progression of metastasis. This research aims to better understand the formation of brain metastasis which may lead to new therapeutic strategies for prevention.

Dr. Gan is developing computational methods to leverage the approximate spatial information of whether a brain cell is near a metastatic tumor cell and coarse tumor progression indicators, such as the postinoculation time and whole-brain ex vivo bioluminescence signal to infer the trajectories of phenotypic states in each type of cell. She is applying these methods to examine how the different populations of cells influence each other to co-evolve along their respective trajectories.

Project title: "In situ single-cell dissection of the tumor-microenvironment interplay mediating brain metastasis"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Joan Massagué, PhD, and Dana Pe'er, PhD
Cancer Type: Brain, Breast, Lung
Research Area: Systems Biology
Tristan Wold Owens, PhD

Dr. Owens focuses on heat shock proteins (HSPs) and their “master regulator” called heat shock transcription factor 1 (HSF1). The transformation and growth of cancers causes a wide array of cellular stresses including metabolic changes, genomic instability, and protein misfolding that would halt the growth of a normal cell. Tumor cells, however, depend on cellular stress response machinery, like HSPs, for their survival. HSF1 is critical to tumor development and progression, and HSF1 activity is strongly correlated with poor prognosis in many common cancers. For decades, efforts to develop cancer therapies targeting HSPs have failed. Dr. Owens aims to understand how HSPs and HSF1 interact to regulate activity, and how this regulation is co-opted to promote tumor growth and progression.

Project title: "Molecular mechanisms of heat shock transcription factor 1 in cancer"
Institution: University of California, San Francisco
Named Award: Suzanne and Bob Wright Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David A. Agard, PhD
Cancer Type: Other Cancer, Breast, Prostate, All Cancers
Research Area: Biochemistry
Sangeetha M. Reddy, MD

Despite the success of immunotherapies such as immune checkpoint blockade in other solid tumors, breast cancer patients have shown limited responses, especially in cases of metastatic disease. Antigen-presenting cells, critical to initiate anti-tumor immunity and for efficacy of immune checkpoint blockade, are known to be defective in breast cancers. Dr. Reddy's research focuses on restoring effective antigen presentation to enhance anti-tumor immunity in breast cancers. Based on data generated in her lab, she is leading a clinical trial to test the combination of chemotherapy with two therapeutic molecules that promote different aspects of antigen presentation. This trial will assess the safety, clinical efficacy, and pharmacodynamics associated with this triplet therapy. Through this work, she hopes to improve long-term survival of patients with triple negative breast cancer and lay the foundation for systemically targeting antigen presentation as a therapeutic strategy in solid tumors.

Project title: "Multi-modality approach to enhancing antigen presentation in breast cancers"
Institution: University of Texas Southwestern Medical Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Zhijian (James) Chen, PhD, and Hans Hammers, MD, PhD
Cancer Type: Breast
Research Area: Immunotherapy
Runmin Wei, PhD

Dr. Wei is focusing on inflammatory breast cancer (IBC), an aggressive disease subtype without known genetic signatures. This suggests that IBC could be highly heterogeneous (the cells within a tumor are genetically diverse), and the tumor microenvironment (the environment surrounding a tumor) may be important for disease progression and therapeutic resistance. He is developing a computational toolkit to characterize the IBC tumor spatial heterogeneity and tumor microenvironment. He will leverage cutting-edge deep learning approaches to associate histopathology findings from tumor samples with single cell spatial sequencing information. This project will provide a better understanding of IBC initiation, progression and therapy responses at a molecular level.

Dr. Wei will use open-access single cell and spatial sequencing data analysis tools, e.g. Seurat and Scanpy to analyze data. He will also use specific computational tools for different analytical purposes, e.g. RNA Velocity and Monocle to infer cell differentiation, CytoTRACE, SCENT to infer cell differentiation potentials, and SCENIC to infer the transcriptional factors and gene regulatory network. Besides, he will develop novel algorithms/computational tools for spatial and single-cell sequencing data analysis.

Project title: "Integrating single cell genomic and spatial information to delineate tumor heterogeneity and microenvironment interactions in inflammatory breast cancer"
Institution: The University of Texas MD Anderson Cancer Center
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Nicholas E. Navin, PhD, and Ken Chen, PhD
Cancer Type: Breast
Research Area: Bioinformatics
Yi Yin, PhD

Dr. Yin has developed single-cell assays that will be combined with statistical modeling to understand homologous recombination (HR). Cells use the process of HR to accurately repair harmful breaks that occur on both strands of DNA. Failure to correct such DNA damage can play a role in cancer initiation and progression. Dr. Yin aims to understand this critical mechanism to help guide treatment approaches for many cancer types.

Project title: "Global analysis of DNA break repair by single-cell sequencing"
Institution: University of California, Los Angeles
Award Program: Dale Frey Scientist
Cancer Type: Blood, Breast, Skin
Research Area: Chromosome and Telomere Biology
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