Urmila Sehrawat is a postdoctoral researcher at Memorial Sloan Kettering Cancer Center. She investigates the regulatory nodes of protein synthesis to identify novel therapeutic vulnerabilities in cancer for personalized, first-in-class treatments. In this Postdoc Portrait interview, she shares how she is taking a different approach to find targets for cancer therapeutics.
Targeting the Cellular Assembly Line
Q | What drew you to protein synthesis in cancer?
I have always been fascinated by the central dogma of biology, but what truly drew me to this field was a striking clinical irony: While protein synthesis is the most energy-intensive process in a cell and is notoriously hijacked by cancer, we have almost no therapies that target it directly. I was drawn to the study of translation because of its sheer complexity and its role as the final gatekeeper of gene expression. In cancer research, we often focus on DNA, but I became captivated by the protein synthesis. Seeing how aggressively cancer cells deregulate this machinery to produce oncogenes convinced me that the most effective way to stop a tumor is to intervene at the point of production. I chose this field because it allows me to combine deep mechanistic biology with the practical, high-impact goal of identifying first-in-class small-molecule inhibitors and using them in targeted therapeutic approaches for personalized treatments.
Q | What scientific problem are you trying to solve?
While it is well established that cancer cells exploit protein synthesis to fuel their rapid growth and adaptability, this pathway remains a remarkably underexplored therapeutic target. Currently, there are no clinical therapies capable of specifically inhibiting this process without significant off-target effects. My work addresses this by investigating the underlying regulatory nodes that become subverted in cancer. Through the identification of novel small molecules that target specific translation factors, I am developing an approach to selectively shut down the production of key oncogenes. By cutting off the supply of functional proteins at the source, my research seeks to transform our understanding of cancer’s exploitation of protein synthesis into a viable, first-in-class treatment strategy.
Navigating Molecular Dialogue
Q | What’s one thing you learned from working with translation factors that you didn’t expect?
Ten years ago, when I started studying translation during my PhD, I didn't anticipate the subtlety needed for selectivity. I initially thought that finding a small molecule to inhibit a translation factor would be a simple lock-and-key challenge. However, I discovered that translation factors are part of a highly dynamic communication network. A molecule might block one factor but could unintentionally activate a backup pathway elsewhere. This realization helped me understand that translation factors operate together as a complex system, and targeting this system might be crucial to selectively inhibit the translation of certain oncogenes. Additionally, some genes rely heavily on specific translation factors for their protein synthesis, and nature provides examples where blocking certain translation factors is vital for survival. This experience showed me that targeting the central dogma of biology involves more than halting a machine—it requires navigating a fluid and adaptive biological dialogue.
Q | If your research succeeds, what could it change for science or society?
If this research succeeds, it will establish a whole new category of cancer treatments. For years, our efforts have been centered on targeting DNA mutations, but many of these targets have been considered undruggable. Demonstrating safe and selective intervention at the protein synthesis level offers a novel approach to drug development. This shift would transform our understanding by moving focus from the genetics of cancer to its protein output, potentially providing a method to treat aggressive cancers that have not responded to existing therapies.
Q | What question are you most excited to answer next?
I’m eager to address whether we can we turn these molecular breakthroughs into a first-in-class treatment for aggressive, undruggable tumors. While our current models show promising results, the real challenge lies in translating a successful small molecule from a dish into an effective therapy within a complex biological system. Understanding how these inhibitors perform in a real clinical setting is crucial for truly improving patient outcomes.
Responses have been edited for length and clarity.
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