Nisha Sosale, a researcher in Associate Professor Matt Lazzara’s cell signaling engineering lab at the University of Virginia’s chemical engineering department, has received a Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellows from the National Cancer Institute. It will fund Sosale’s project, “Investigating the role of SPRY2 in regulating drug resistance of glioblastoma multiforme tumors and interaction between GBM tumor cells and macrophages.”
The fellowship, often referred to as an NCI F32 award, “supports promising postdoctoral applicants who have the potential to become productive and successful independent cancer research investigators,” according to the National Cancer Institute website. The NCI, which is part of the National Institutes for Health, is the federal government’s principal agency for cancer research and training.
Sosale’s project will build on her work in Lazzara’s lab, where she has held a postdoctoral appointment since 2015 when they were at the University of Pennsylvania. Lazzara joined the faculty at UVA’s School of Engineering and Applied Science in 2016.
"The work that we do in the Lazzara Lab is appealing because we use chemical engineering principles to better understand biological molecules in a way that helps us to discover improved therapeutic treatments for cancer."Nisha Sosale, NCI individual fellow
Glioblastoma multiforme — which is often shortened to GBM — is the most common and lethal brain cancer in adults. Standard of care includes surgery and radiation or chemotherapy, but even with these treatments, patients survive only 12 to 15 months.
In previous research, Lazzara’s lab has demonstrated that the protein Sprouty2, or SPRY2, which has been reported to function as a tumor suppressor in some cancers, surprisingly functions as a driver of tumorigenesis in GBM.
“High levels of Sprouty2 also correlate with poor patient survival,” Sosale said. “Further studies from our lab have shown that reducing levels of Sprouty2 in a controlled manner leads to more [tumor] cell death in response to existing therapeutics, which indicates that Sprouty2 hinders the effectiveness of therapeutic molecules used to treat GBM.”
For example, Sosale said they have seen reductions in Sprouty2 increase cell death in response to targeted inhibitors of oncogenic proteins known to drive GBM pathogenesis.
More recently, a second element of their research has shown that Sprouty2 could play a role in communication between GBM cells and tumor-associated macrophages. “Sprouty2 may control this cell-cell communication by regulating the release of proteins into the extracellular space. The proteins can be sensed by macrophages and can regulate macrophage phagocytosis, a cellular engulfment process through which macrophages can destroy cancer cells,” Sosale said.
In both phases of the investigation, the researchers will use Luminex, a system that utilizes antibody-coated microbeads to capture and to detect and quantify multiple signaling proteins simultaneously. “Using a computational model, we will identify which of the measured signals are most strongly associated with Sprouty2’s ability to drive GBM resistance to therapeutics and regulation of macrophages.”
The ultimate goal is to translate this knowledge into new treatment modalities to improve glioblastoma multiforme patient survival. The promise of such outcomes drew Sosale to Lazzara’s work. She met him at UPenn when he served on her dissertation committee. She had completed a postdoctoral appointment at the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany, when Lazzara received an American Cancer Society grant that allowed him to hire a researcher.
“After hearing about the exciting work, I was very interested to join the lab,” Sosale said. “The work that we do is appealing because we use chemical engineering principles to better understand biological molecules in a way that helps us to discover improved therapeutic treatments for cancer.”