Through her research, Mojgan Naghavi, PhD, associate professor of Microbiology-Immunology, investigates how microtubules, regulators of microtubule dynamics and microtubule motor proteins, function to enable HIV-1 movement in an infected cell. In one recent study, her lab infected cells with fluorescently tagged HIV to track the virus from the time it entered the cell, all the way through to the nucleus, where the virus replicates.
Her team also explores how and why HIV infection induces neuronal damage, in the hope of helping to develop potential new approaches to treat HIV-associated dementia.
What are your research interests?
Our research focuses on infection by Human Immunodeficiency Virus type 1 (HIV-1), a retrovirus and causative agent of acquired immunodeficiency syndrome (AIDS). In addition to suppressing the immune system, rendering victims susceptible to opportunistic infections, HIV-1 can cross the blood-brain barrier and cause serious damage to the central nervous system, ultimately leading to HIV-associated dementia.
Our research has had a long-term focus on host factors that regulate HIV-1 infection in a variety of cell types, including microglia and primary neurons. Our early work discovered that the neuronal protein FEZ-1 regulates early HIV-1 infection. We have since gone on to show that FEZ-1 acts as a microtubule (MT) motor adaptor protein that associates with HIV-1 capsids and regulates inward movement of viral particles to the nucleus. We have also uncovered fundamental aspects of how HIV-1 regulates MT behavior to facilitate infection and the host factors involved. This includes MT plus-end binding proteins and actin-MT cross-linkers involved in initiating virus transport. Moreover, we discovered that HIV-1 infection was regulated by PDZD8, a poorly understood protein whose biological function was unknown prior to our discovery of its role in regulating MT stability. Beyond HIV-1, we have also discovered how neurotropic viruses such as Herpes Simplex Virus type 1 (HSV-1) exploit MTs to facilitate their replication.
What types of collaborations are you engaged in across campus (and beyond)?
Our long-time collaborator is Derek Walsh, PhD, in the Department of Microbiology-Immunology here at Northwestern. Together with his lab, we have discovered how HSV-1, the causative agent of cold sores, corneal blindness and encephalopathy, exploit MTs to facilitate their replication. We also collaborate with Stephen Goff, PhD, another retrovirologist, as well as cell biologists Gregg Gundersen, PhD, and Richard Vallee, PhD, at Columbia University to understand how HIV and HSV-1 hijack host MT network and MT motors for their movement in infected cells. We are doing this as part of an NIH-funded Program Project Grant (PPG) between our five labs.
How did you become interested in this area of research?
I became interested in HIV as a student at Karolinksa Institute in Stockholm, Sweden. At that time, in the early 1990s, we knew very little about the virus and with the lack of combination antiretroviral drugs currently available to keep HIV infection under control, AIDS was a major cause of death globally. I really wanted to get involved in trying to understand this new disease and try to make a contribution. I later became interested in HIV motility in infected cells when I discovered a number of MT regulatory host factors that could regulate HIV infection during my postdoctoral training at Columbia University.
How is your research funded?
Our research is funded by National Institute of General Medical Sciences, awards R01GM101975 (Characterization of the antiviral and nuclear functions of FEZ-1 and NEK-1) and P01GM105536 (Microtubule networks and virus trafficking), as well as National Institute of Allergy and Infectious Diseases, award T32 AI007476 (Immunology and Molecular Pathogenesis Training Program). We are also supported by Northwestern University and NUCATS start-up awards.
Where have you recently published papers?
We recently published some of our work showing how FEZ-1 binds to HIV cores and regulates the movement of viral particles towards the nucleus in Nature Communications. In collaboration with Dr. Walsh we also uncovered how HSV-1 regulates MT dynamics to initiate their intracellular transport during early infection. This work was recently published in the Journal of Cell Biology.
Who inspires you?
There are a number of people who inspire me, but I would have to say that my former postdoctoral mentor, Stephen Goff, is one who springs to mind immediately. He works on diverse subjects, yet manages to make groundbreaking contributions to each field. He has an enduring passion for science. He is incredibly successful, and at the same time, he is hugely supportive and helpful towards young researchers establishing their own groups, making him truly inspirational.