Date: March 21, 2011
Shyam Biswal, Ph.D.
A Timeline of CRF Discovery
• 2001: A cigarette exposure facility is constructed to study smoking-induced lung cancer.
• 2002: The work reveals new information about smoking-related carcinogens and the cellular changes they cause that ultimately lead to lung cancer.
• 2003: Biswal and team identify and test chemopreventive agents that block the negative impact of smoke on cells.
• 2004: He identifies the Nrf2 gene and finds that it helps detoxifies cells of carcinogens, such as cigarette smoke. Nrf2 directs proteins to absorb pollutants and chemicals and then pumps them out, clearing cell of toxins.
• 2005-2007: Another gene, called Keap1, is found to work with Nrf2. Keap1 lets cells know when toxins are removed, shutting down Nrf2.
The team learns that lung cancer cells corrupt the Nrf2/KEAP1 process. Biswal finds that an altered Keap1 gene keeps Nrf2 active pumping out cancer-attacking drugs before they can get into lung cancer cells.
Biswal used these findings to leverage additional grants from the National Institutes of Health and the Flight Attendant Medical Research Institute.
JHU reports three discoveries. Two international patent applications are based on this work.
• 2008-2010: Biswal collaborates with a University of Maryland investigator to screen 1280 compounds for their ability to block Nrf2 in lung cancers with Keap1 mutations. The best candidate becomes the focus of clinical trials funded by the National Cancer Institute.
TODAY: This novel therapeutic approach to target lung cancer treatment resistance has resulted in three inventions licensed to the Baltimore, Maryland-based start-up company Cureveda. Patents are pending in the U.S., Canada, Europe, and Australia. It is unlikely that this progress would have been made without the initial CRF grant.