Dr. Andrew J. Flint has been the director of the NExT Chemical Biology Consortium (CBC) Support Program since 2016, after joining the Frederick National Laboratory for Cancer Research as a senior scientist and technical project manager in 2011.
Flint has a Ph.D. in biochemistry from University of California, Berkeley, and a B.S. in chemistry from the University of North Carolina at Chapel Hill. Prior to working on diverse oncology targets in the NExT CBC program, his research career focused on regulation by protein phosphorylation. As a graduate student, he identified sites of autophosphorylation on protein kinase C bII, one isozyme of the recently discovered receptors for the tumor-promoting phorbol esters. His pioneering use of the baculovirus expression system, which has now become standard practice, enabled studies with purified, fully active individual mammalian PKC isozymes.
As a postdoctoral fellow with Nick Tonks at Cold Spring Harbor Laboratory, Flint studied PTP1B, the founding member of a recently discovered class of novel phosphotyrosine dephosphorylating enzymes. He collaborated with David Barford to determine its X-ray crystal structure, providing the first views of the conserved 3-dimensional structure of the catalytic domain that defines this family of enzymes. His enzyme kinetic studies with a variety of mutants in conserved residues revealed their roles in catalysis and led to the invention of substrate-trapping mutants for discovery of PTP substrates.
In 1996, he was hired as the fourth employee at the biotech company CEPTYR, Inc., which was founded to exploit PTPs as therapeutic targets. There, he initially developed assays to characterize the mechanism of action of PTP inhibitors, and to exclude agents acting via a surprisingly large array of bogus, artifactual, or undesirable mechanisms. As leader of the biochemical pharmacology group, his team worked on all targets being prosecuted, but he was most involved with the PTP1B project for diabetes and obesity, leading a collaboration with Eli Lilly in the early stages, and eventually chaperoning the selected clinical candidate into IND-enabling studies and overseeing its synthesis and cGMP manufacturing.
