Northwestern University Assistant Professor Judd Hultquist, PhD, was recently awarded an R21 grant from the National Institute of Allergy and Infectious Diseases to study new molecular probes for understanding HIV latency and for developing next-generation curative strategies. Hultquist is a principal investigator of this grant, along with Ali Shilatifard, PhD, the Robert Francis Furchgott Professor and chair of biochemistry and molecular genetics at Northwestern.
“This award really is the product of a highly synergistic collaboration between Dr. Shilatifard’s lab, which brings expertise in drug design and transcriptional regulation, and my lab, which brings expertise in HIV molecular virology and latency,” said Hultquist.
Antiretroviral therapies for the treatment of HIV are not curative because the virus can hide in long-lived cells in the human body. These “latently infected” cells silence expression of the virus through many different mechanisms that prevent the immune system from recognizing and clearing them. Identifying ways to wake these viruses up is one way that they could be cleared from the body, leading towards the development of an HIV cure.
Recently, the Hulquist lab, in collaboration with Shilatifard’s lab, described a new role for the protein complex PAF1C in regulating HIV latency. To better understand the contribution of PAF1C to latency, Hultquist and Shilatifard’s labs developed a small molecule inhibitor of PAF1C, which they showed could reactivate latent viruses in blood from people living with HIV. With this award, Hultquist and Shilatifard aim to optimize this inhibitor to make it more efficient, research its mechanism of action, and determine if it might have synergistic potential with other ongoing cure strategies being used in the HIV field.
Over the last several years, Hultquist has been very involved with the Third Coast Center for AIDS Research and its Viral Pathogenesis Core, providing consultation on the practical application of high-throughput and systems-level approaches to molecular virology. The Third Coast CFAR has helped him create ideas for new HIV research projects.
“The idea for this project originated with a CFAR Administrative Supplement Award in 2020, which provided the seed funding to develop and test the first inhibitor we used in a variety of latency models,” said Hultquist.
Hultquist values the countless opportunities that interdisciplinary work provides for cutting-edge HIV research and innovations.
“I think this research project is a great example of how interdisciplinary collaborations that bridge expertise and bring new investigators into the HIV field can lead to new innovations, ideas, and progress.”Judd Hultquist