Research Awards Research Awards: Developing Cyclopeptide Nef Inhibitors to Facilitate HIV-1 Eradication

$ 538,606 awarded to Xiaofei Jia sponsored by The National Institute of Health

Pictured above, left to right: 
Back: Jacob Kress, Mohammad Karimian Shamsabadi*, Dodhy Saint-Amand, Xiaofei Jia
Front: Madelyn Davis* (graduated), Arianna Klimczyk (graduated), Fatema Yeasmin*, Priya Sridharan*, Kequan Wang*
^{*Students working on or having contributed to this project}

Assistant Professor Xiaofei Jia has been awarded $538,606 by the National Institute of Health (NIH) for the project, "Developing Cyclopeptide Nef Inhibitors to Facilitate HIV-1 Eradication"

This project is being pursued collaboratively by a team of three research groups: Dr. Rudi Fasan’s group at University of Rochester, Dr. John Guatelli’s group at University of California San Diego, and Dr. Jia’s research group at UMass Dartmouth. UMass Dartmouth is the primary and contact site of this R56 grant. The R56 Award, to be shared by the three groups, will provide limited, interim research support based on the merit of the pending application. This support is designed to enable the Principal Investigator to gather additional data for revision of the current application.

This project is directed toward developing a novel antiretroviral drug that could potentially help cure HIV infection. While currently available antiretrovirals can control HIV infection, they cannot eliminate it, which means that there is still no cure of this disease. Part of the difficulty in finding a cure for HIV is that the virus has devised mechanisms to hide the infection from the host immune system. Previous work on the viral protein Nef has elucidated, at the molecular level, how Nef enables immune evasion in two significant ways.

"Inspired by our finding that Nef is poised to bind short peptides that bend themselves into near-circular shapes, we have designed this current project to develop cyclic peptide (or cyclopeptide) inhibitors to block Nef functions," said Jia. "The promise is that such drugs, if developed successfully, may help revitalize immune mechanisms, which are otherwise silenced by Nef, to spot infected cells and then possibly clear them.

"This is a very exciting project that we have worked enthusiastically on for a while. Although our results are so far promising, we are only at the very beginning of a hopefully long journey. It is very possible that we find out somewhere down the road that such a drug cannot be developed. However, we do feel that, given the promise and potential here, this path has to be explored. I feel fortunate that we could be the ones to test this out, for our own scientific careers and for the world.

"I am very grateful that the NIH recognizes the significance of our work and has committed to support us with the interim grant. I hope that, with the help of NIH and the efforts of our three groups, we could further validate this approach. To me, the goal this year is to convince the funding agency, and ourselves, that this work ought to be continued."