Skip to main content.

Grantees

2024 Lion Heart Grant recipients

 

Lion Heart’s Core Granting Criteria

A Lion Heart grant has become – within the research community of the Yale Cancer Center, Smilow Cancer Center/ Yale New Haven – an important accolade for the careers of researchers and thus the advancement of breast cancer solutions. This is because our funding principles has proven to be both attractive to donors and to our research grantees:

  • Seed Funding - One-year grants:  Our grants are meant to be awarded only time and for one year.  The goal of the grant is to investigate new ideas and hypotheses in order to build a case for larger grants.  Thus, our Lion Heart dollars are leveraged to become far larger than the actual grant amount suggests.
  • Young researchers – We aim our grants primarily at young breast cancer researchers or researchers who move from other fields of research into breast cancer research. Our grants have supported major careers of various recipients, who have developed new clinical applications and breakthroughs in the fight against breast cancer.
  • Tracking Impact – While grants are for one year, we track the progress and impact of our grants over time, in order to measure the success of our funding principles and the longer term impact of our grants.

 

Grantees for 2025

The Lion Heart grant committee met in December, 2024 to review and select the 2025 research grants. For 2025, we awarded three $ 52,000 research grants.

Mapping the Spatial Landscape of Immune Response and Tumor Heterogeneity to Predict Immunotherapy Efficacy in Triple Negative Breast Cancer

Principal Investigator: Thazin Aung, PhD. Associate Research Scientist, Dept. of Pathology, Yale School of Medicine.

Immune modulation therapies are effective tools in managing triple negative breast cancer (TNBC), but they do not help all TNBC patients and are quite expensive. It is important to find ways to identify the patients who are likely to respond before treatment, so that they can be offered other therapies. Spatial biology analyzes the characteristics of cancer cells, immune cells and other cells in tumors in the context of their relative locations in tissue. This provides a new window into the local neighborhood of cancer cells that can have enormous impact on their behavior. For example, the presence or absence of specific subsets of nearby immune cells may predict response to immune-based therapies. Dr. Aung will perform digital spatial profiling on a collection of TNBC cases from two different treatment cohorts and use advanced machine learning techniques to develop a signature that predicts response to immune checkpoint therapy. An innovative component of this work is integration of the spatial biology results with microscopic imaging of tumor sections stained with hematoxylin and eosin dyes for diagnosis of TNBC.

Deriving information from two different kinds of tissue analyses will multiply the predictive power and utility of the signatures for management of TNBC. Moreover, this work will advance deeper computational exploitation of information in standard stained tissue images that are inexpensive and are acquired routinely for clinical practice. The computational principles established will be readily applicable to other types of breast cancer besides TNBC, and to other cancers treated with immune-based therapies. This work will support the pathway to career independence of a talented young breast cancer investigator.

Mechanism of PLA2G10 in Inducing the Immune Evasion and Resistance to Immunotherapies of Triple- Negative Breast Cancer

Principal Investigator: Tianxiang Zhang, PhD. Associate Research Scientist, Dept. of Immunobiology, Yale University.

Many patients with triple negative breast cancers (TNBC) do not respond to immune therapies such as PD-1 or PD-L1 inhibitors. These tumors often lack sufficient infiltrating T cells to mount an effective immune response, even when that response is ramped up with the immune therapies. In a recent Science Immunology publication, the PI identified PLA2G10 in a screen for molecules that interfere with infiltration of T cells into tumors. The hypothesis is that blockade of PLA2G10 will facilitate tumor penetration by T cells and improve responses to immune therapies. Dr. Zhang’s research will investigate what the major source(s) of the molecule are within tumors, and identify characteristic differences in portions of tumors rich or poor in PLA2G10. These are essential steps towards understanding regulation of PLA2G10, and how it affects the behavior of cancer cells and immune cells. To translate his findings to the clinic, Dr. Zhang plans to evaluate the impact of combining PLA2G10 blockade therapy in combination with immune checkpoint therapies that augment limited endogenous anti-tumor immune responses. Finally, Dr. Zhang will determine the impact of PLA2G10 blockade on tumor infiltration by a different immune-based therapy, CAR-T therapy. CAR-T therapies use T cells that are modified by genetic engineering so that they will attack specific kinds of tumors. They are approved by the FDA for use in some leukemias, but have been largely ineffectual on solid tumors including TNBC. A major obstacle seems to be limited infiltration of the CAR-T cells into tumors, which should be improved by PLA2G10 blockade.

Overall, PLA2G10 blockade therapy is on a rapid path to clinical trials. This work will advance preclinical investigation of an exciting new immune agent that may overcome a major obstacle to immune therapies. Dr. Zhang intends to continue professional development towards independence at the juncture of laboratory and clinical science leading to new breast cancer therapies.

Novel Treg inactivating approach for breast cancer immunotherapy via targeted protein degradation

Principal Investigator: Wei Hu, PhD. Assistant Professor of Immunobiology, Yale School of Medicine.

Immune checkpoint therapies have had some utility for treatment of breast cancer, especially triple negative breast cancer. These agents dial up existing anti-tumor responses, but may be ineffectually when the patients’ existing T cell control of the tumors is limited, or has been exhausted. The magnitude of the anti-tumor immune controlling an individual patient is a balance of many influences that affect the activity and location of CD8 T cells that can kill tumor cells. A different set of T cells termed regulatory (Treg) cells plays an important role in negative regulation of immune responses including those mediated by tumor killing T cells. Treg cells are essential for protection from auto-immune diseases in which the immune system attacks the patients’ tissue. Potentially, reduction of Treg would enhance anti-tumor CD8 responses, but this might result in massive autoimmunity. Dr. Hu has shown, using sophisticated animal modeling, that loss of the Foxp3 protein required for Treg development leads to an amount of reduced Treg function in which immunity is maintained and enhanced, but without obvious autoimmune disease. She will first determine the impact of Foxp3 suppression on immune responses to a series of breast cancer cell lines. Next, she will develop a small molecule protein degrader agent (using molecular glue technology) that will selectively degrade Foxp3 in human cells.

This work builds upon Dr. Hu’s establishment that Foxp3 targeting to suppress Treg cells can be accomplished in animal models without overwhelming auto-immune disease. The planned work will model this approach for immune-based breast cancer control and initiate development of a small molecule agent for this purpose. This innovative work will establish a new therapeutic angle to enhance immune control of breast cancer. This funding supports an innovative young investigator in early stages of academic career development as a translational immunologist.

See more research grantees.