Sarah Slavoff has received a 2022 Mark Foundation Emerging Leader Award for her research into a cryptic class of human genes called small open reading frames – some of which are critical regulators of cancer cell signaling pathways and inflammation – that might be linked to adverse treatment outcomes in melanoma. The award, from The Mark Foundation for Cancer Research, aims to empower scientists to take on innovative, high-risk, high-reward projects that have significant potential to improve outcomes for cancer patients.
Dr. Slavoff’s laboratory at Yale’s Institute of Biomolecular Design and Discovery develops chemical and biological tools to study the “dark matter of the human genome” – previously undiscovered small open reading frames that encode microproteins – and their functions. Many patients with metastatic melanoma, the deadliest of skin cancers, develop resistance and other adverse responses to treatment. While the mechanisms behind such adverse events are inadequately understood, uncovering the role of microproteins might introduce new diagnostic and therapeutic targets to revolutionize the treatment of this devastating disease.
“Many metastatic melanoma patients can’t be cured by the current standard of care, and the genetic and molecular causes of these treatment failures are largely unknown,” said Slavoff, assistant professor of chemistry and of molecular biophysics and biochemistry. “We think some of the dysregulated molecules that make cancers refractory to treatment are microproteins, which is why they were previously unidentified – they weren’t part of the genome annotation. This could also suggest that microproteins are linked to human disease more broadly.”
The Slavoff lab, which is based at Yale’s West Campus, expect their findings to enable novel approaches for diagnosing and treating melanoma.
Sarah Slavoff obtained her Ph.D. from Massachusetts Institute of Technology in 2010, where she developed new tools for fluorescence microscopy and proximity biotinylation of cellular proteins in the laboratory of Dr. Alice Ting in the Chemistry Department. She was a NIH Ruth L. Kirchstein Postdoctoral Fellow with Dr. Alan Saghatelian at Harvard University from 2010 – 2014, where she developed the first proteomic method to discover human microproteins on a large scale, and characterized the MRI/CYREN microprotein, which regulates DNA repair. She came to Yale as a faculty member in 2014.
The Mark Foundation for Cancer Research is a philanthropic organization that funds research to transform the prevention, diagnosis, and treatment of cancer. The annual Emerging Leader Awards is granted to promising early-career investigators for projects aimed at addressing unmet needs in cancer research.
Learn about the Slavoff Lab.