Projects 11713

Cause: cancer

Study of the biophysical effects of cancer mutations of histone methyltransferase SETD8

In project 11713 we are looking at histone lysine methyltransferase SETD8 in the context of its cancer mutations. This protein has been found overexpressed in a number of cancers including bladder cancer, non-small cell and small cell lung carcinoma, chronic myelogenous leukemia, hepatocellular carcinoma, and pancreatic cancer. In some cancers, it has been found to promote tumorigenesis, and it has been implicated in cancer invasiveness and metastasis [DOI: 10.1186/s13148-016-0268-4]. In a series of past and current projects we have been interested in understanding the conformational landscape of SETD8 in as much detail as possible, so that eventually selective small molecule inhibitors and chemical probes can be designed and tested. In this particular project we aim to explore the effect of over 20 mutations seen in cancer patients on the stability of SETD8 in its active conformation.

List of Contributors

This project is managed by Rafal Wiewiora at Memorial Sloan Kettering Cancer Center.


Graduate Student at Chodera Lab, Memorial Sloan Kettering Cancer Center, New York.

Interested in studying conformational dynamics of proteins using Molecular Dynamics and experimental methods, to make rational drug design better, cheaper and faster. Working with histone methyltransferases - a family of epigenetic regulators implicated in many cancers, aging and drug addiction.

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