UF researcher receives grant to study gene involved in pediatric cancers

By Ian Bennett | bennettian@ufl.edu

With funding from a Live Like Bella® Pediatric Cancer Research Initiative grant, Steven Bruner, Ph.D., a professor in the department of chemistry in the University of Florida College of Liberal Arts & Sciences, will research detrimental mutations in the human SRP54 gene that cause inherited bone marrow failure syndromes and progression of pediatric cancers. 

Steven Bruner, Ph.D.

SRP54, also known as signal recognition particle 54, is a protein that plays a critical role in maintaining the proper function of cells through the synthesis and transport of proteins. SRP54 is a central component of the signal recognition particle, which mediates the co-translational/trafficking of proteins through the endoplasmic reticulum. Mutations in the signal recognition particle have been linked to a variety of diseases, including cancers, autoimmune disorders, neutropenias, neurodegeneration and infectious diseases. However, the exact mechanisms by which these mutations lead to disease development are not fully understood.  

The aim of this research is to gain a better understanding of the molecular basis of how SRP54 functions and how congenital mutations lead to human disorders. The new project is a collaboration between the Bruner Lab and Carl Denard, Ph.D., an assistant professor in the UF department of chemical engineering and a member of the UF Health Cancer Center’s Cancer Therapeutics & Host Response research program.  

Carl Denard, Ph.D.

“We are thrilled to receive this grant and are excited to work on this important area of research,” said Bruner, who is also a member of the Cancer Therapeutics & Host Response research program. “SRP54 plays a crucial role in key cellular processes and congenital mutations of the gene have recently been linked to human disorders. A better understanding of the role that these mutations play in neutropenia and leukemias will be invaluable in the development of treatments for diseases associated with SRP54 mutations.”  

Through the new grant, the team will develop a novel methodology to study the molecular and genetic basis of SRP54 dysfunction and provide leads for therapeutic intervention. The ultimate goal is to develop novel therapeutic and diagnostic approaches to treat or predict diseases associated with SRP54 mutations. 

The expertise of the Bruner and Denard laboratories in enzyme structure/mechanism and synthetic biology will be critical in the development of biochemical and cell-based assays for the research. To study the function of SRP54 and its interactions with pathway proteins, they will work together to develop engineered yeast as a model system for discovering phenotypes of clinically relevant SRP54 mutations. Then, the team will develop small molecule probes into the function or dysfunction of these mutations.   

They will also investigate the effects of congenital mutations on protein function and in disease development and progression. This work will provide a better understanding of congenital mutations of SRP54 and initiate a long-term program focused on how SRP54 mutations affect neutrophil progenitor cells and lead to leukemia.  

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