Paras Gaur is a postdoctoral researcher at the University of Iowa. His work focuses on unraveling the complex mechanisms of DNA damage, repair, and genome stability. In this Postdoc Portrait interview, he discusses how cells prevent the genomic instability that often drives cancer progression and explains the importance of his work in guiding future translational cancer therapeutics.
Resolving Noncanonical DNA Structures for Genome Stability
Q | What scientific problem are you trying to solve?
My favorite project focuses on understanding how cells process G-quadruplexes (G4s), which are noncanonical DNA structures that regulate transcription and replication but can drive genome instability when unresolved. These structures are particularly relevant in breast cancer, where they contribute to intratumor heterogeneity and therapy resistance. My research investigates how key repair proteins, such as Fanconi anemia group J protein (FANCJ) and poly(ADP-ribose) polymerase 1 (PARP1), coordinate G4 processing and how cancer-associated mutations in these proteins alter repair outcomes.
Q | What is your favorite part of conducting this research?
What excites me most is combining cutting-edge approaches like single-molecule total internal reflection fluorescence (TIRF) microscopy, mass photometry, and cryo-electron microscopy to visualize these interactions in real time. So far, I have learnt that PARP1 binds selectively to certain G4s and undergoes robust auto-PARylation, a finding that opens new questions about structure-specific signaling and drug sensitivity. By integrating biochemical, single-molecule experiments with structural studies, this project aims to uncover mechanisms that could be exploited for personalized cancer therapies. The potential to translate these insights into novel therapeutic strategies makes this work deeply rewarding.
A Global Journey in Mechanistic Cancer Research
Q | What drew you to studying DNA structures?
My interest in science began early in school but it started to really become reality during my undergraduate studies, where I studied applied zoology. Exposure to research during this time deepened my curiosity, leading me to seek hands-on experience with zoologist Sharmila Basu-Modak, and later at the National Institute of Immunology, studying molecular phylogeny of biliverdin reductase. These experiences solidified my commitment to research.
During my PhD, I focused on DNA damage repair and drug discovery, developing high-throughput assays to study proliferating cell nuclear antigen ubiquitination and identify inhibitors of the translesion synthesis pathway. Currently, as a postdoctoral fellow in Maria Spies’s lab, I investigate how proteins like FANCJ process G4 DNA structures using single-molecule biophysics and structural biology. These experiences shaped my goal of leading a research program that translates mechanistic insights into therapeutic strategies for cancer.
Q | What are some memorable experiences that guided your development as a scientist?
The most exciting part of my scientific journey has been its diversity and the growth it fostered. Starting in Delhi and now working as a postdoctoral fellow in the United States, I’ve trained across India, Hungary, and the US, which has shaped my adaptability and broadened my perspective towards life and science. Each transition brought new challenges and opportunities from learning fundamental biochemistry during my PhD in Hungary to mastering single-molecule biophysics and structural biology in my current role.
What excites me most is the ability to connect mechanistic insights to translational cancer therapeutics. My work on DNA damage repair and G4 structures has opened avenues for understanding therapy resistance and identifying new drug targets. Beyond research, leading programs like the Postdoctoral Association travel award and serving on the University Research Council have strengthened my leadership and advocacy skills. These experiences have not only advanced my science but also prepared me to build an inclusive, impactful research program as an independent investigator.
Q | If you could be a laboratory instrument, which one would you be and why?
I would be a single-molecule TIRF microscope. It is a tool that lets you see real molecular events in real time. It reveals dynamics that bulk assays often miss. It gives precision without losing context. It shows interactions that drive DNA repair, replication, and genome stability. It is also fun to watch cool lasers at work.
TIRF microscopy reflects how I work. I focus on details that matter. I value clarity and sensitivity. I like to uncover complexity without creating noise. I want to enable discovery at the most fundamental level and turn molecular events into clear, interpretable results.
Responses have been edited for length and clarity.
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