Professor of Biology and Chemistry
Ph.D., Brandeis University
My laboratory uses approaches derived from both chemistry and biology to investigate molecular mechanisms of cellular biochemistry and physiology. Projects are organized around the themes of purine/pyrimidine metabolism and protease action and include problems in inhibitor design, protein engineering and cellular metabolism. Most projects have clinical relevance. Techniques vary with the particular project, and can entail molecular biology, single molecule experiments, organic synthesis, protein crystallography and NMR spectroscopy as well as protein purification, enzyme kinetics and mutagenesis.
Sample of Recent Publications
Umejiego NN, Gollapalli D, Sharling L, Volftsun A, Lu J, Benjamin NN, et al. Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis. Chem Biol. 2008;15(1):70-7.
Riera TV, Wang W, Josephine HR, Hedstrom L. A kinetic alignment of orthologous inosine-5'-monophosphate dehydrogenases. Biochemistry. 2008;47(33):8689-96.
Mortimer SE, Xu D, McGrew D, Hamaguchi N, Lim HC, Bowne SJ, et al. IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA. J Biol Chem. 2008;283(52):36354-60. [full text in PubMed Central]
Hedstrom L. IMP dehydrogenase-linked retinitis pigmentosa. Nucleosides Nucleotides Nucleic Acids. 2008;27(6):839-49.
Liu L, Mushero N, Hedstrom L, Gershenson A. Short-lived protease serpin complexes: partial disruption of the rat trypsin active site. Protein Sci. 2007;16(11):2403-11.
Gladysheva IP, Sazonova IY, Houng A, Hedstrom L, Reed GL. Regulation of nonproteolytic active site formation in plasminogen. Biochemistry. 2007;46(30):8879-87.
Rejman D, Olesiak M, Chen L, Patterson SE, Wilson D, Jayaram HN, et al. Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase. J Med Chem. 2006;49(16):5018-22.
Liu L, Mushero N, Hedstrom L, Gershenson A. Conformational distributions of protease-serpin complexes: a partially translocated complex. Biochemistry. 2006;45(36):10865-72.
Hedstrom L, Gan L. IMP dehydrogenase: structural schizophrenia and an unusual base. Curr Opin Chem Biol. 2006;10(5):520-5.
Bowne SJ, Sullivan LS, Mortimer SE, Hedstrom L, Zhu J, Spellicy CJ, et al. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2006;47(1):34-42. [full text in PubMed Central]