Srinivasu Karri is a postdoctoral researcher at the University of Minnesota. He investigates how cells accurately recycle parental histones during DNA replication to maintain critical chromatin states. In this Postdoc Portrait interview, he shares what initially drew him into the world of chromatin inheritance and how a better understanding of this process can potentially guide new therapeutics strategies.
Uncovering Chromatin Inheritance Networks
Q | What drew you to epigenetics and molecular biology?
My interest in this field stems from the fundamental importance of chromatin state inheritance in preserving epigenetic information during cell division. While DNA replication ensures genetic fidelity, the faithful propagation of chromatin states is equally critical for maintaining cell identity. Dysregulation of this process is increasingly linked to developmental disorders and cancer, motivating my focus on uncovering the underlying mechanisms.
Q | What scientific problem are you trying to solve?
My research revolves around uncovering how parental histones are accurately recycled during DNA replication to preserve epigenetic information. While DNA replication ensures genetic fidelity, the mechanisms that maintain chromatin states—particularly how histones are transferred to leading and lagging strands—remain unclear. Resolving this will provide fundamental insight into genome regulation and its disruption in disease.
Q | What’s one thing you learned from your research that you didn’t expect?
I initially thought that histone transfer during replication was mainly driven by proteins with histone-binding motifs. However, I learned that this process is far more dynamic and regulated. Multiple factors, including replication stress, chromatin context, and checkpoint signaling, can significantly influence how histones are transferred to newly replicated strands.
Mapping Future Therapeutic Strategies
Q | If your research succeeds, what could it change for science or society?
This work will redefine how epigenetic information is propagated during DNA replication and how its disruption contributes to disease. By uncovering mechanisms of nascent chromatin inheritance, this research will provide critical insight into cancer heterogeneity, aging, and neurological disorders, potentially revealing new therapeutic strategies to modulate epigenetic states.
Q | What question are you most excited to answer next?
I want to understand whether we can tune the machinery that copies and repairs DNA using external signals, potentially opening new ways to treat disease.
Responses have been edited for length and clarity.
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