Xiaofei Jia awarded two NIH R01 grants to study HIV-1 eradication

Biochemistry professor wins two R01 grants in two months

The Jia Lab from L to R Top: Kequan Wang, Fatema Yeasmin, Linh Dan Nguyen, Priya Sridharan, Ruth BarbosaAmado Bottom: Xiaofei Jia, Mohammad Karimian Shamsabadi, Dodhy Saint-Amand, Jacob Kress

Associate Professor of Chemistry and Biochemistry Xiaofei Jia, PhD was recently awarded a four-year R01 grant with a first-year budget of $701,761 from the National Institutes of Health (NIH) for, "Developing Cyclopeptide Nef Inhibitors to Facilitate HIV-1 Eradication." The project was originally awarded an R56 grant from the NIH in August 2022.

This marks Jia's second R01 grant awarded by the NIH in the past two months. In July, he was awarded a five-year grant for a related project, "Elucidating the Structural Bases of HIV-1-Induced CD4 Degradation," with a first-year budget of $531,301.

"This is very exciting for my lab," said Jia. "Our research has two components, and the two new grants each provide multi-year support for one component of our work. The first component of our research involves using structural biology to understand how HIV-1 evades the immune system. The R01 grant that came in July will help us further understand structurally how the virus utilizes multiple strategies to take down an important host immune receptor, named 'CD4.'

"Once we understand through our structural work how certain immune evasion is achieved by the virus, we may then be able to engage with the second component of our research – developing therapeutics to target and possibly clear the viral infection. In essence, our goal is to therapeutically reactivate the host immune mechanisms so that infected cells can be identified and killed by the empowered immune cells. The R01 grant awarded on August 1 supports our efforts here. In this project, we're working on developing cyclopeptide-based therapeutics, a novel type of drug with immense potential.

"Receiving funding for both components of our research means that we can continue to keep things balanced, which is great in many senses, including for student training."

While currently available antiretrovirals can control HIV infection, they cannot eliminate it, which means that there is still no cure for 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. The work in the Jia Lab explores one possible route of finding a cure.

Earlier structure solved in the Jia Lab revealed that the conformation of the HIV-1 protein Nef responsible for downregulating CD4 (cartoon, cyan) is incompatible with Nef dimerization (two protomers of the dimer are in blue and red, respectively).

"Drug discovery is high-risk, high-reward," said Jia. "Brilliant ideas fail most of the time, but there's no way to know without trying it. We believe that this direction should be explored experimentally and we're very grateful that the NIH recognizes the value of our work and is supporting our efforts with these multi-year grants.

"The cyclopeptide project is pursued collaboratively by three research groups: Dr. Rudi Fasan’s at the University of Texas at Dallas, Dr. John Guatelli’s at University of California San Diego, and our group here at UMass Dartmouth, which will serve as the primary and contact site

"As a team, we first applied for this grant a year prior. However, we had a challenging time convincing the reviewers of its practicality. The NIH program officer, recognizing the potential of our project, issued us a one-year R56 grant so that we could gather more data to further validate our approach. The support of the R56 interim grant was tremendous in maintaining this large collaboration."

The National Institutes of Health is the largest public funder of biomedical research around the globe. Their support has led to life-saving treatments and an ever-growing body of research that paves the way for future breakthroughs. The Research Project Grant (R01) is the original and historically oldest grant mechanism used by NIH, providing support for health-related research and development based on the mission of the NIH.

Associate Professor of Chemistry and Biochemistry Xiaofei Jia, PhD

Jia Lab members at all levels—PhD, master’s, and undergraduate—are contributing to these projects. PhD students Jacob Kress, Mohammad Karimian Shamsabadi, Priya Sridharan, Kequan Wang, BS/MS students Dodhy Saint-Amand, Ruth BarbosaAmado, and rising junior Linh Dan Nguyen have contributed to and/or are working on the structural biology project; PhD students Mohammad Karimian Shamsabadi, Fatema Yeasmin, and Kequan Wang have contributed to and are continuing to work on the cyclopeptide inhibitor development project.

"We have a team of young, enthusiastic students who are eager to learn and keen on producing solid research," said Jia. "These projects are great training grounds for them. It's exciting to think how much they will grow in the process. Of course, I hope to be able to grow a little as well myself, learning together with, and sometimes from, my students.

"Before, the pressure was on securing funding to support our work; now it has switched to delivering the results and proving to the reviewers and the NIH that we are worth supporting. That’s what we will be focused on doing in the next few years."

Read more about Dr. Jia's work at The Jia Lab.

Contact:
DavidJames
508-999-8478
djames2@umassd.edu

Source: https://www.umassd.edu/news/2023/xiaofei-jia-two-r01-grants.html

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