Bio
Nathanael Gray is the Krishnan-Shah Family Professor of Chemical and Systems Biology at Stanford, Co-Director of Cancer Drug Discovery Co-Leader of the Cancer Therapeutics Research Program, Member of Chem-H, and Program Leader for Small Molecule Drug Discovery for the Innovative Medicines Accelerator (IMA). His research utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anti-cancer targets. Dr. Gray’s research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance.
Dr. Gray received his PhD in organic chemistry from the University of California at Berkeley in 1999 after receiving his BS degree with the highest honor award from the same institution in 1995. After completing his PhD, Dr. Gray was recruited to the newly established Genomics Institute of the Novartis Research Foundation (GNF) in San Diego, California. During his six year stay at GNF, Dr. Gray became the director of biological chemistry where he supervised a group of over fifty researchers integrating chemical, biological and pharmacological approaches towards the development of new experimental drugs. Some of the notable accomplishments of Dr. Gray’s team at GNF include: discovery of the first allosteric inhibitors of wild-type and mutant forms of BCR-ABL which resulted in clinical development of ABL001; discovery of the first selective inhibitors of the Anaplastic Lymphoma Kinase (ALK), an achievement that led to the development of now FDA-approved drugs such as ceritinib (LDK378) for the treatment of EML4-ALK expressing non-small cell lung cancer (NSCLC); and discovery that sphingosine-1-phosphate receptor-1 (S1P1) is the pharmacologically relevant target of the immunosuppressant drug Fingomilod (FTY720) followed by the development of Siponimod (BAF312), which is currently used for the treatment of multiple sclerosis.
In 2006, Dr. Gray returned to academia as a faculty member at the Dana Farber Cancer Institute and Harvard Medical School in Boston. There, he has established a discovery chemistry group that focuses on developing first-in-class inhibitors for newly emerging biological targets, including resistant alleles of existing targets, as well as inhibitors of well-validated targets, such as Her3 and RAS, that have previously been considered recalcitrant to small molecule drug development. Dr. Gray’s team developed covalent inhibitors of the T790M mutant of EGFR inspired the development of Osimertinib (AZD9291), now FDA approved for treatment of patients with relapsed lung cancer due to resistance to first generation EGFR inhibitors. Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called "gatekeeper" residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR.
In 2021, Dr. Gray joined Stanford University where he has joined the Stanford Cancer Institute, Chem-H and the Innovative Medicines Accelerator (IMA) to spur the development of prototype drugs.
These contributions have been recognized through numerous awards including the National Science Foundation’s Career award in 2007, the Damon Runyon Foundation Innovator award in 2008, the American Association for Cancer Research for Team Science in 2010 and for Outstanding Achievement in 2011 and the American Chemical Society award for Biological Chemistry in 2011, and the Nancy Lurie Marks endowed professorship in 2015 and the Paul Marks Prize in 2019, and the Hope Funds for Cancer Research in 2023.
