Spotlight Article featuring Zac Nagel

 

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EMGS celebrates its LGBTQIA+ scientists during June Pride Month. In recognition of these scientists and as a final celebration of Pride Month, please enjoy this article spotlighting Zac Nagel, Assistant Professor at the Harvard T.H. Chan School of Public Health and member of the EMGS Diversity and Inclusion Committee. Thank you to Catherine Klein for taking the time to craft these interview questions, and to Zac Nagel for his thoughtful answers.

 

Can you tell us about your research?

Research in our laboratory is focused on understanding how the pathways responsible for maintaining genome integrity affect our susceptibility to the health effects of DNA damage and the response of cancers to therapy. At the core of our work are functional assays that I originally co-developed during my postdoctoral research in Leona Samson’s laboratory at MIT. Fluorescence multiplex host cell reactivation (FM-HCR) assays utilize fluorescent reporter plasmids modified with site-specific DNA lesions to measure DNA repair capacity in mammalian cells. We are continuing to expand the repertoire of DNA repair processes that can be measured with these reporters. We have now developed reporters for microhomology mediated end joining, translesion synthesis, joining of double strand breaks with chemically complex structures, reporters that can distinguish between subpathways of nucleotide excision repair, and reporters that measure the accuracy of double strand break repair.

We are applying this technology in several areas where genome integrity is emerging as an important and underexplored dimension of public health. These applications include screening engineered nanomaterials for potential genotoxicity, determining how inter-individual differences in DNA repair capacity affect susceptibility to lung cancer and clinical radiosensitivity, and predicting therapeutic responses in glioblastoma multiforme. We have several exciting collaborations with EMGS members that are focused on basic mechanisms of DNA damage tolerance and repair. For example, we’re investigating structure-function relationships in REV7 together with Graham Walker. We have also been studying DNA repair mechanisms in cancer cells with Natalie Gassman and Joann Sweasy, and we are measuring DNA repair in populations in collaboration with Bevin Engelward. In the longer term we hope this work will collectively advance personalized medicine by providing insights into individual susceptibilities and determining which therapies are most likely to work for individual cancer patients.

 

When did you know what kind of career that you wanted?

I wish I could say I always knew I wanted to be a scientist, but in fact curiosity is what came first. Once I started doing undergraduate research, I realized that doing experiments was the most gratifying way to satisfy my curiosity. And as I got further into my career, I realized it was also possible to make useful tools and answer important questions about human health. That’s what I do now in my dream job, and it makes sense in hindsight, but I’d never have guessed I’d be here 20 years ago.

 

Did your career involve any missteps, or divergences?

I’ve taken a winding path, but I don’t regret it. I got my start studying photosynthesis at the University of Michigan. My PhD project in chemistry was about the role of quantum tunneling in enzymatic catalysis in Judith Klinman’s laboratory at UC Berkeley. So, moving to Leona Samson’s laboratory at MIT for my postdoc was quite a leap, but that experience opened my eyes to the possibility that we can do basic and applied research at the same time. Now at the Harvard T.H. Chan School of Public Health, I find I can apply everything I learned along the way, which gives me a unique perspective on public health.

 

Were there any LGBTQ issues that impacted your career choices?

As we close out pride month, I’m grateful for the progress we’ve made since I started my career. Being a member of this community is a source of joy for me, and fortunately it did not impact my career choice even though a common perception in the late 90s was that being openly gay could be a career killer. For many of us it does come with some challenges, including growing up worrying about how we’re perceived, and whether we’ll be welcome. Since peer review is at the core of the scientific enterprise, I think this primes us for experiencing the imposter syndrome. For me the antidote has been to surround myself with supportive people, and I’m proud to say EMGS has been a wonderfully supportive community.

 

What advice would you offer to upcoming young scientists?

Change your mind often. It’s good to keep your mind flexible so you don’t miss the message when some surprising or even disappointing data come from your experiments. I think this is good advice for life in general; when new information comes in, we should be open to the possibility that we’ve been wrong about something, even if we’re really attached to it. Whether it’s a trivial matter or a major life decision, I find that changing my mind as I learn new things is one of the most satisfying exercises!

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