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Fred Perrino, PhD

Fred Perrino, PhD, is exploring the dysfunction of the TREX1 and TREX2 genes and the enzymes they encode in causing autoimmune disorders. He is also researching the anticancer potential presented by inhibiting their function, thereby stimulating an immune response. He is eager for industry support in his efforts to identify small molecules that will exploit this unique cancer immunotherapy strategy.

About Fred Perrino

Perrino earned his PhD in biological sciences at the University of Cincinnati in 1986. From 1986 to 1989, he was a postdoctoral fellow in pathology and biochemistry at the University of Washington, Seattle. He joined Wake Forest University Health Sciences as an assistant professor of biochemistry in 1989, was promoted to associate professor in 1995 and became a full professor in 2006. He also serves as director of the molecular and cellular biosciences track for the Wake Forest School of Medicine.

Decades ago, Perrino and his lab colleagues identified the TREX1 and TREX2 genes. TREX1 encodes an enzyme that is especially potent in dismantling DNA, which is an essential physiological function. As his work progressed, he determined that mutation in the TREX1 gene leads to the development of autoimmune disorders, because failure to degrade DNA by TREX1 activates the immune system. Now, with the entire TREX1 pathway defined, he is pursuing the possibility that inhibiting the catalytic activity of TREX1 with a small molecule could stimulate a powerful anti-cancer immune response—a new form of cancer immunotherapy.

The concept that drove Perrino’s research forward is that humans do not evolve genes with the kind of catalytic potential seen in TREX1 and TREX2 without there being very important biology at work. Over the years, he has relentlessly pursued a comprehensive understanding of this biochemical system, and his eventual acquisition of that knowledge has brought about exciting new opportunities in immunooncology. Perrino and his team are also studying the cellular and molecular elements that drive autoimmunity, using a mouse model with a TREX1 mutant allele that causes a lupus-like phenotype when present in humans.

Perrino would like to partner with industry to identify small molecule inhibitors of TREX1. He believes the modality may represent an entirely new approach to cancer immunotherapy, with the potential for substantial therapeutic, scientific and commercial benefits. Developing the immunooncology strategy will require investment in the ongoing research to bridge the basic science with clinical applications with tremendous potential to enhance human health.


Fred Perrino, PhD, professor of biochemistry at Wake Forest School of Medicine and track director of the Molecular and Cellular Biosciences Graduate Program, specializes in:

  • The biochemistry of DNA and RNA in human disease
  • Human autoimmune diseases
  • Lupus
  • The role of enzymes in human autoimmune diseases
  • The TREX1 and TREX2 genes, which encode DNA disassembly enzymes