Venuprasad Poojary, Ph.D.

A study researching the impact of inflammation on tumor progression was recently published in Nature Immunology featuring the work of Venuprasad Poojary, Ph.D., assistant professor of Immunology and Microbiology for the Wayne State University School of Medicine.

The paper, "The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation," presents three years of research studying two enzymes -- E3 ligase Itch and deubiquitinase Cyld -- and how they work together to prevent the spread of metastasis  in mice with lung cancer.

Chronic inflammation has been associated with tumor growth, yet there has not been a clear understanding of why this happens. Dr. Poojary, also a researcher at the Barbara Ann Karmanos Cancer Institute, and his research team identified that the interaction of the two enzymes studied (the Itch-Clyd complex), promoted the degradation of the protein kinase, called Tak1, an intracellular signaling component in inflammatory signaling pathways. This interaction helped to terminate the signaling process that encourages tumor growth.

The findings of Dr. Poojary's research team suggest that deficiencies in the enzymes Itch or Cyld led to the chronic production of tumor-promoting cytokines (small cell-signaling protein molecules) advancing the growth and metastases of lung carcinoma in lab mice. Research findings demonstrated that the Itch-Clyd combination of enzymes helped prevent inflammatory cells in mice with lung cancer.

Although the research is ongoing, Dr. Poojary said, the results are significant. The next step will be to determine whether this shows promise in mice with other cancers, and then how this work translates to human cancer tissue.

"We have discovered a novel Itch-Cyld ubiquitin editing complex that terminates inflammatory pathway," Dr. Poojary said. "We are investigating the role of this complex in the regulation of tumor growth in mouse models of human cancers. Our ultimate goal is to target this novel pathway to inhibit tumor promoting inflammation that may help prevent the spread of certain cancer diseases."

In addition to Dr. Poojary, other researchers involved in this work from the WSU School of Medicine and the Karmanos Cancer Institute include Neesar Ahmed, Ph.D.; Minghui Zeng, Ph.D.; Indrajit Sinha, Ph.D.; Lisa Polin, Ph.D.; and Wei-Zen Wei, Ph.D. Also involved are Chozhavendan Rathinam, Ph.D., from Columbia University Medical Center in New York; Richard Flavell, Ph.D., from Yale University School of Medicine in Connecticut; and Ramin Massoumi, Ph.D., from Lund University in Sweden.