Members of the Hart lab use the tools of single crystal X-ray diffraction, together with other biophysical and biochemical methods, to characterize the structure and action of macromolecules involved in human health. Current projects include the RNA lariat debranching enzyme (ALS), copper-zinc superoxide dismutase (ALS), community acquired respiratory distress syndrome (CARDS) toxin Mycoplasma pneumoniae (asthma/ARDS); and matrix metalloproteinase-13 (osteoarthritis). We seek mechanisms to combat schistosomiasis, a disease caused by parasitic blood flukes that infect ~200 million people world-wide. Each project has a translational component, and we work closely with the UTHSCSA Center for Innovation in Drug Discovery in the structure-based pursuit of novel therapeutic agents. Dr. Hart serves as Director of the UTHSCSA X-ray Crystallography Core Labortatory (http://xray.uthscsa.edu).
Gleason JE, Galaleldeen A, Peterson RL, Taylor AB, Holloway SP, Waninger-Saroni J, Cormack BP, Cabelli DE, Hart PJ, Culotta VC. Candida albicans SOD5 represents the prototype of an unprecedented class of Cu-only superoxide dismutases required for pathogen defense. Proc Natl Acad Sci U S A. 2014 Apr 7.
Ivanova MI, Sievers SA, Guenther EL, Johnson LM, Winkler DD, Galaleldeen A, Sawaya MR, Hart PJ, Eisenberg DS. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):197-201.
Valentim CL, Cioli D, Chevalier FD, Cao X, Taylor AB, Holloway SP, Pica-Mattoccia L, Guidi A, Basso A, Tsai IJ, Berriman M, Carvalho-Queiroz C, Almeida M, Aguilar H, Frantz DE, Hart PJ, LoVerde PT, Anderson TJ. Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites. Science. 2013 Dec 13;342(6164):1385-9.
Galaleldeen A, Taylor AB, Chen D, Schuermann JP, Holloway SP, Hou S, Gong S, Zhong G, Hart PJ. Structure of the Chlamydia trachomatis immunodominant antigen Pgp3. J Biol Chem. 2013 Jul 26;288(30):22068-79.
Seetharaman SV, Winkler DD, Taylor AB, Cao X, Whitson LJ, Doucette PA, Valentine JS, Schirf V, Demeler B, Carroll MC, Culotta VC, Hart PJ. Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R. Biochemistry. 2010 Jul 13;49(27):5714-25.