First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Nima Taefehshokr is first author on ‘ SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2’, published in JCS. Nima conducted the research described in this article while a Postdoctoral Associate in Bryan Heit's lab at the Department of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, Canada, where his work revolved around investigating how SARS-CoV-2 suppressed MHC II expression. He is now a Scientific Evaluator at Health Canada, Ottawa, Canada.

Nima Taefehshokr

How would you explain the main findings of your paper in lay terms?

One way that the virus that causes COVID-19, SARS-CoV-2, could disrupt our immune system's ability to fight it is by reducing the number of molecules that show pieces of the virus, known as antigens, to our immune cells. These molecules, called MHC II proteins, help our immune system recognize and attack the virus. In this paper, we looked into how this process works in our cells, and I found that a main SARS-CoV-2 protein called NSP5 is responsible for decreasing the levels of MHC II. NSP5 does this by stopping another protein in our cells called CIITA from working properly. CIITA normally helps MHC II do its job, but NSP5 messes with it. NSP5 usually functions by cutting up virus proteins, but I found that NSP5 can also bring another protein called HDAC2 to CIITA. HDAC2 then changes CIITA in a way that stops it from working. When CIITA doesn't work, MHC II can't do its job either, which means that fewer antigens are shown to our immune cells. This mechanism slows down our immune system's ability to recognize and fight the virus. I showed that if we can get our cells to make more CIITA or block HDAC2, we can help our immune system get back on track to better fight the virus.

Were there any specific challenges associated with this project? If so, how did you overcome them?

I had to introduce NSP5 into various immune cells using a lentivirus system to investigate the expression of MHC II. This was tricky because immune cells don't always easily take up genetic material, and keeping them alive during the process is tough, especially for cells in suspension. In total, it took ∼3 months to optimize this step. Despite facing challenges with experiments, including our live virus experiments, we tackled them by tweaking each step until it worked well.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

During the early stages of the project, I conducted one of the very first experiments to evaluate the effect of NSP5 on the MHC II antigen presentation system. I visually observed, using a microscope, a suppression of MHC II expression in cells expressing NSP5, which was marked with a green indicator. This discovery fueled our curiosity to further investigate the mechanism underlying this effect.

Why did you choose Journal of Cell Science for your paper?

We chose Journal of Cell Science for my paper because we have encountered high-quality peer-reviewed JCS papers in the fields of biology and immunology, and because JCS provides a platform for dissemination to a wide audience of researchers and professionals.

Subcellular localization of SARS-CoV-2 NSP5 after inhibition of importin-mediated nuclear import.

Subcellular localization of SARS-CoV-2 NSP5 after inhibition of importin-mediated nuclear import.

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Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Absolutely. Mentors play a crucial role in our professional and personal development. Dr Li, my PhD mentor, provided pivotal guidance in shaping my scientific mindset by emphasizing critical thinking and instilling effective problem-solving strategies. Similarly, Dr Heit's unwavering support throughout my postdoctoral journey has been invaluable. His mentorship extended well beyond the confines of the lab, providing guidance on navigating career transitions, seizing networking opportunities and fostering personal growth. Dr Heit's mentorship was characterized by his holistic approach.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

My journey into science was sparked by my dad, a laboratory scientist, who introduced me to the wonders of microscopes and the thrill of experimentation from a young age. His passion for science was infectious, and I found myself engrossed in meaningful discussions with him about everything from biology to philosophy. Additionally, personal experiences, like losing my grandmother to cancer and witnessing my uncle battle autoimmune disease, provided me with deeply personal motivations for delving into the realm of scientific inquiry. Throughout my undergraduate and MSc studies, winning various awards solidified my passion for research and science, motivating me to pursue a PhD. These achievements served as milestones, reinforcing my belief in the power of scientific exploration to address real-world challenges. Each step along my path, from conducting experiments in the lab to evaluating the safety of pharmaceutical products, has been filled with intriguing moments that have deepened my appreciation for the complexities of the natural world.

Who are your role models in science? Why?

My scientific role models are intellectuals who have made substantial contributions to our comprehension of the world and unraveled the mysteries of the universe through their revolutionary discoveries and innovative approaches. Examples include, among others, Charles Darwin, Rosalind Franklin, Edward Jenner, Louis Pasteur, Galileo Galilei, Isaac Newton and Albert Einstein.

What's next for you?

Currently, I work as a scientific evaluator at Health Canada, where I assess the safety and effectiveness of cancer drugs entering the Canadian market. Our team ensures that risks associated with these drugs are communicated transparently to healthcare professionals, empowering the public to make informed decisions. My aim is to gain more experience in this field and contribute further to this important work. My current role allows me to have a significant impact on public health, and I'm committed to continuing this work. As for what's next, I plan to continue advancing in this field, leveraging my expertise to contribute to public health initiatives and ensure the safety of pharmaceutical products for the Canadian population.

Tell us something interesting about yourself that wouldn't be on your CV

About 6 years ago, I went bowling for the first time with a group of 15 people who were seasoned bowlers and confident in their skills. Despite not hitting any pins for the first three rounds, I didn't give up. Instead, I stayed focused and determined, learning quickly from my mistakes. Eventually, my perseverance paid off, and I hit several strikes, ending up winning the game despite the rough start. This experience reminds me of the importance of quick learning and adaptation, qualities that have proven valuable in various aspects of my life.

Nima Taefehshokr's contact details: Health Canada, 200 Eglantine Driveway, Ottawa, Canada.

E-mail: [email protected]

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2024
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SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2
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J. Cell. Sci.
137
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jcs262172
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