2010

Michael Lin MD, PhD

Stanford University Human Gene Therapy Division, Stanford, CA Assistant Professor, Departments of Pediatrics and Bioengineering

Research Focus: Tumor Specific Replicating Viruses and Bacterium

Cancer Type: Brain & Breast Cancers

Award: Young Investigator

The measles vaccine virus, which has an impeccable safety record from decades of clinical use, has a natural preference for binding and infecting many types of tumor cells. It has proven promising in clinical trials for several forms of cancer. Recently, genetic modifications to the measles vaccine virus that enhance its ability to replicate in cells provide further evidence of greater efficacy to kill tumors. However, as this therapeutic virus platform is modified to be more lethal to cancer cells, it is crucial to be able to restrict its replication in order retain low toxicity to normal cells.

This research aims to develop two mechanisms for improving measles vaccine virus control and specificity. The first allows administration of an orally available non-toxic drug to rapidly shut off virus protein production. The second renders virus protein production dependent on a specific molecular abnormality commonly found in cancer cells. Both will be based on encoding in the virus genome rationally engineered protein switches to control the function of viral replication proteins. In preliminary work, Dr. Lin has successfully created prototypical control elements for both mechanisms. He proposes to test the ability of these control elements to function in the context of the whole virus in order to control replication in time and by tumor type. If successful, the proposed work will establish a generalized method by which replication of measles vaccine virus, and other RNA-based viruses, can be programmed for increased tumor specificity and safety.

Dr. Michael Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, Damon Runyon-Rachleff Innovation Award, and a 2013 NIH Pioneer Award.

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