Biomedical Engineering (BME) graduate student Anujan Ramesh has been selected to receive the 2022 Student Award for Outstanding Research from the Society for Biomaterials. He and his advisor Ashish Kulkarni of the Chemical Engineering Department (and a BME adjunct) have been working on reprogramming certain immune cells called macrophages to inhibit tumor growth much more effectively.
The Society for Biomaterials award to Ramesh is part of its program to recognize significant contributions to the field of biomaterials science from industry, academia, regulatory agencies, and students. A paper submitted by Ramesh and Kulkarni to the society’s Journal of Biomedical Materials Research Part A (JBMRA) was one of the main criteria for Ramesh’s award and is still under review for placement in the journal.
As Ramesh says about his research, “My area of interest is primarily in the field of immune engineering. My research focuses on identifying novel targets involved in immune cell-disease cell interactions, engineering supramolecular nanoparticle systems that can modulate immune cell response in order to resolve disease associated with the immune system, and developing tools to monitor the efficacy of treatments in real-time.”
In that context, Ramesh is a member of the Kulkarni Research Group, which works at the interface of engineering and immunobiology to develop innovative technologies for achieving the precise level of immune activation to treat diseases and improve human health.
As Kulkarni and Ramesh explain about the research described in their JBMRA paper, “Macrophages are ubiquitously present cells that are a part of the innate immune system and are the first line of defense against incoming pathogens. In addition to this, macrophages also infiltrate the tumor micro-environment of solid tumors in high numbers. These ‘tumor associated macrophages’ [TAMs] are cells capable of existing in multiple phenotypes….”
The researchers go on to explain that recent developments in the field of macrophage immunotherapy have focused on strategies aimed at reeducating TAMs from two particular phenotypes to act more effectively against tumors. But, so far, data from such studies demonstrate that the TAMs still exhibit subpar anti-cancer performance due to nonspecific biodistribution, toxicities, and low therapeutic indices.
The research of Kulkarni and Ramesh aims to upgrade this reeducation process.
According to Kulkarni and Ramesh, “We hypothesized that TAMs can be reprogrammed metabolically by delivery of drugs using a supramolecular nanoparticle [that can] effectively rewire macrophage metabolism by simultaneous inhibition of the Citric Acid Cycle and upregulation of the glycolytic metabolic pathway.”
As the researchers conclude from their experimentation based on this hypothesis, “In summary, we have demonstrated the synthesis of a metabolic supramolecular nanoparticle system that can deliver dual drugs targeting two different metabolic targets in TAMs.”
According to Kulkarni and Ramesh, “These results were further validated in an aggressive murine 4T1 breast-cancer model, where decreased tumor burden was observed [because of] of metabolic reprogramming of TAMs in the tumor microenvironment. Ex vivo studies that were performed evaluated the immune profile of tumor infiltrating macrophages to further attest to the tumor progression data.”