As a protein crystallographer by training, my interests lie of course in determining and analyzing 3D atomic structures of proteins, especially proteins that are of interest in all stages of disease such as cancer, with the purpose of understanding the function/malfunction that causes the disease/cancer. More recently, after moving to UAB's School of Dentistry, my research topics have expanded to cover proteins involved in formation of hard tissue and enamel during tooth formation and development as well as proteins involved in the bacterial colonization of teeth that cause caries.
One main focus of research is the signaling system of pleiotrophin. Pleiotrophin (PTN) is a secreted heparin-binding cytokine that signals diverse functions, including lineage-specific differentiation of glial progenitor cells, neurite outgrowth, and angiogenesis. The gene expression of PTN, also known as HB-GAM, and osteoblast-specific factor 1 (OSF-1) is found in cells in early differentiation during developmental periods and is up-regulated in cells with an early differentiation phenotype in wound repair. ptn is also a proto-oncogene, which is strongly expressed in different human tumor cells and expression of the ptn gene in tumor cells in vivo accelerates growth and stimulates tumor angiogenesis. We are working towards elucidation of the three-dimensional structures of the protein complexes involved in the PTN signaling pathway.
A second focus is on biophysical characterization of the enamel matrix proteins, exemplified by ODAM (Odontogenic and ameloblast-associated molecule) and amelogenin, both expressed in the ameloblasts during the maturation stage of enamel formation.
Third, we recently determined the three-dimensional structure of Streptococcus parasanguinis Gtf3 glycosyltransferase as a collaboration with Professor Hui Wu (UAB School of Dentistry). This project may ultimately lead to development of small-molecule oral bacterial-secreted glycosyltransferase inhibitors, which can be used to prevent caries.
Another recently developed project is the structural investigation of transcription factor/DNA interactions (Msx1/Pbx1) involved in tooth and bone formation and development. This is a collaboration with Dr. Peter Jezewski (UAB School of Dentistry). Msx1 proteins are ancient members of the Metahox subset of homeobox domain-containing transcription factors. The Metahox genes act as master control genes during body plan development. The Msx1 gene is expressed in all vertebrates, including humans, within cranial neural crest cells that form the face and jaws, and is also known to regulate tooth development. The Msx1 protein is a transcriptional repressor and a mouse knock-out model of Msx1 shows an oral facial clefting phenotype, as well as missing teeth. The Msx1 5’-upstream regions contains a short nucleotide sequence that is highly conserved in vertebrates from humans to zebra fish, and is believed to be a distal enhancer of Msx1 expression. Interestingly; the distal enhancer region contains a consensus-binding motif for both the Msx1 and Pbx1 transcription factors. We are characterizing binding interactions between the Msx1, Pbx1 proteins and the upstream Msx1 distal enhancer region (double stranded DNA (dsDNA)) using various biophysical techniques, including protein X-ray crystallography and Isothermal Titration Calorimetry (ITC).
Dr. Erlandsen (b. 1970) received her Ph.D in protein crystallography from the University of Tromsø, Norway, in 1998. She worked under the guidance of Professors Asbjørn Hordvik and Edward Hough and determined the structure of human phenylalanine hydroxylase (PAH), an important enzyme in the metabolism of dietary phenylalanine, as well as characterized ligand binding and effects of mutations in the enzyme both structurally and biophysically. Mutations in the gene for PAH are known to cause phenylketonuria (PKU), one of the first recognized inborn errors of metabolism (PKU is an autosomal recessive genetic disorder). Dr. Erlandsen did her post doctoral research at the University of California at Berkeley and The Scripps Research Institute (Califormia, USA) with professor Raymond C. Stevens, before taking a faculty position as an assistant professor at the Department of Biochemistry and Biophysics at Stockholm University, Sweden. She moved to Birmingham in 2007 and her primary faculty appointment is currently as a research instructor at the Institute of Oral Health Research in the UAB School of Dentistry. She is a secondary faculty member at the Department of Chemistry at UAB. Her work is currently funded through the NIDCR.