Daniel A. Engel, PhD
Function of the adenovirus E1A oncoprotein
Adenovirus oncoprotein E1A function (collaborations with Cancer Center members A. Beyer, J. Brown and B. Paschal labs). The Engel lab has been studying the function of the adenovirus E1A oncoprotein, which is a transcriptional regulator of viral and cellular genes. They have found that the E1A interacts directly with the major viral core DNA binding protein, protein VII, suggesting that E1A regulates viral transcription through modification of viral chromatin structure. They are examining the function of protein VII during virus replication to determine how viral chromatin structure plays a part in this process. This work relates to the interplay between chromatin regulation and cancer, which has been documented in a number of systems. They are doing EM studies with the Brown lab to examine the structure of protein VII-DNA complexes. They are doing mammalian cell microinjection studies with the Paschal lab to examine the function of protein VII-DNA complexes in the nucleus. The lab has published a recent paper with the A. Beyer lab demonstrating the activity of protein VII as a DNA condensation protein and repressor of transcription.
Drug discovery and characterization of novel anti-cancer Therapeutics (collaborations with M.M. Smith, Grant labs) Chromatin structure and its regulation play important roles in cellular control and oncogenesis. They are using a "synthetic lethal" approach to identify novel compounds that target chromatin regulatory pathways in yeast. Compounds identified so far include inhibitors of histone acetyltransferases. Genetic (with Smith lab) and biochemical (with Grant lab) approaches are being applied to identify the pathways targeted by positive acting compounds.