We use cross-disciplinary
approaches to understand
and engineer cell-cell interactions in human brain tumors.
Decoding Cell-Cell Interactions:
Unraveling the Complexity of Tumor Biology
Tumors are complex biological systems made up of multiple, diverse, and interconnected malignant and non-malignant cell components capable of being reactive to a changing environment.
Cell-cell interactions play essential roles in determining cell identity and function important for the malignant properties of human tumors. Research in our laboratory is focused on understanding how cells interact and communicate with their surrounding environment and how cells process environmental inputs to exert functions.
Dissecting Cellular Diversity and Connections: Pioneering Precision Therapies for Intractable Brain Tumors
Moving towards an exciting and emerging “human biology” era, we are well poised to employ genetic tools, humanized model systems, single-cell technologies, multiplexed assays, and clinical, computational, and engineering expertise. With our ability to measure, model, and manipulate the complex process of cellular communications, our goal is to ascertain the mechanisms of cellular diversity and connection in the complex tumor ecosystem and leverage this knowledge to develop effective and precise therapies for intractable brain tumors, such as glioblastoma.
Inspiring and mentoring the next generation of scientists is one of our missions, and in turn, they will bring a fresh perspective for future medicine. Our young collaborator’s idea below and drawing from her high school research class embody it.
By Neithraa Bacon
The drawing describes genetically modified “super microglia” performing ideal functions to combat glioblastoma. Cancer cells evade attacks from the immune system mainly through the following two mechanisms:
- Avoiding detection from immune cells, and
- Manipulating the immune cells to be dysfunctional.
This proposal shows genetically engineered microglia with four mechanisms to help the immune system identify and attack glioblastoma cells.
- The first mechanism, as shown on the top right of the diagram, allows microglia to recognize where signals are coming from through a receptor protein. Cancer cells deactivate immune cells through inhibitory signals such as PD-L1. Super microglia repurpose the inhibitory signals for detecting glioblastoma cells.
- The second mechanism, described on the bottom right, shows a possible method to recognize glioblastoma cells. Super microglia synthesize a chemical that binds to the proteins that reside within the cell. Glioblastoma has very few mutations and sometimes hides its proteins to avoid recognition.
- The third mechanism, as shown on the bottom left, shows the production of IFN-γ once the cell is identified as abnormal. This cytokine enhances microglia’s tumor suppressive and phagocytic functions. The self-production of IFN-γ will greatly strengthen microglia’s efficiency locally.
- Finally, the fourth mechanism, described on the top left, shows a laboratory-created protein that can specifically activate immune cells. With this protein, there is more efficient communication between immune cells and a quick response to glioblastoma cells.
Our laboratory is affiliated with
Department of Neurosurgery at the University of Michigan Medical School
BioInnovations in Brain Cancer (BIBC) program supported by the Biosciences Initiative
The Hara lab is physically located at the Biointerfaces Institute at the North Campus Research Complex