Henry V Baker
Professor, Department of Molecular Genetics and Microbiology
University of Florida College of Medicine, USA
Dr. Baker’s research focus is in developing gene expression classifiers that can be used to diagnosis illness, predict clinical course and ultimately responsiveness to therapy. Dr. Baker is a participating investigator in Large Scale Collaborative Research Program Inflammation and the Host Response (U54 GM-62118). His laboratory serves as one of three genomic cores for this program. The others are Washington University School of Medicine and the Genomics Center at Stanford University. He is a member of the computational analysis and modeling core of the program. The main goals of this project are using microarrays to determine whether patterns of gene expression from whole blood leukocytes can be used to identify trauma and burned patients at risk of developing MODS.
Investigation of Fundamental Problems of Gene Regulation The goal of our laboratory is to investigate fundamental problems of gene regulation, and to train graduate students for competitive careers as independent research scientists, and in the case of M.D./PhD students to provide physician scientists with rigorous training in the experimental sciences. The accomplishments of the lab are best measured by the accomplishments of the students who have trained here. Our laboratory’s research focus is on the basic process by which cells regulate the expression of their genes. The informational content of all cells lies encoded within the primary DNA sequence. The expression of individual genes is regulated and controlled by a number of transcriptional regulatory proteins that bind at regulatory sites corresponding to the individual genes. Our laboratory uses the yeast, Saccharomyces cerevisiae, as a model cell for which to study combinatorial interactions between the proteins that govern gene expression. We are interested in understanding the precise roles played by various transcriptional proteins as they come together to mediate high-level gene expression. For the past few years we have investigated the nature of the combinatorial interactions between the proteins known as Rap1p and Gcr1p. At yeast Glycolytic gene upstream activating sequence (UAS) elements Rap1p and Gcr1p come together to form some of the strongest promoter elements known. Rap1p serves as a model for a class of multi-functional proteins that can act as either an activator or repressor depending on the sequence context of its binding site. Gcr1p serves as a model for a class of sequence specific transcription factors that displays high-affinity but low-specificity for their binding sites in vitro, yet can find and bind to their sites in vivo. At glycolytic enzyme gene UAS elements Rap1p functions as an activator by facilitating the binding, at adjacent DNA binding sites, of Gcr1p which then mediates activation. Thus the apparent paradoxes raised by Rap1p and Gcr1p are answered by the combinatorial interactions between the two proteins. Rap1p functions as an activator at glycolytic gene UAS elements by facilitating the binding of Gcr1p. Gcr1p’s specificity for its DNA binding site is increased in vivo via cooperative binding interactions with Rap1p. We hypothesize that Rap1p has other binding partners that mediate additional activating functions and its repressing functions. We think it is also likely that Gcr1p may have additional binding partners that may facilitate its binding in a Rap1p independent fashion. We are currently using a global genomic approach to identify other binding partners for both Rap1p and Gcr1p.