个人简介

PEW Scholar in Biomedical Sciences (2010), Blanchard Fellowship (2010), Rosalinde and Arthur Gilbert/ American Federation for Aging Research New Investigator Award in Alzheimer Disease (2009), NSF CAREER Award (2008), Glaucoma Research Foundation Shaffer Award for Innovative Glaucoma Research (2008), American Chemical Society Nobel Laureate Signature Award for Graduate Education in Chemistry (2006), NIH Postdoctoral Research Fellowship (2005)

研究领域

Biochemistry/Biomolecular Structure and Function/Chemical Biology/Molecular Biophysics

We are interested in the molecular details of how cells survive by recognizing and responding to intracellular signals. Eukaryotic cells employ several mechanisms to maintain homeostasis, and if these systems are mis-regulated, changes in metabolite concentrations or protein production/folding eventually lead to a host of diseases. In addition, some of these pathways exist in and are exploited by bacterial pathogens and viruses to gain entry into eukaryotic cells. We seek to understand the details of structure, function, and mechanism of proteins involved in these highly regulated pathways, focusing on enzymes that perform hydrolysis reactions in an unexpected chemical environment: within lipid membrane or near the surface of membranes. In the long term, we hope to identify small molecule inhibitors to modulate these activities and prevent diseases associated with aberrant signaling behavior. Our methods focus on protein crystallography, biochemical and biophysical characterization, in silico modeling, and drug design.

近期论文

查看导师最新文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Donegan, R.K., Hill, S.H., Freeman, D.M., Nguyen, E., Orwig, S.D., Turnage, K.C., Lieberman, R.L. Structural basis for misfolding in myocilin-associated glaucoma. Hum. Mol. Genet. 2014. (DOI: 10.1093/hmg/ddu730) Stothert, A. R., Suntharalingam, A., Huard, D. J., Fontaine, S. N., Crowley, V. M., Mishra, S., Blagg B. S., Lieberman, R. L., Dickey, C.A. Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma. Hum. Mol. Genet. 2014, 23(24), pp. 6470-80. (DOI: 10.1093/hmg/ddu367) Yu, Y., Mena-Barragan, T., Higaki. K., Johnson, J. L., Drury, J. E., Lieberman, R. L., Nakasone, N., Ninomiya, H., Tsukimura, T., Sakuraba, H., Suzuki, Y., Nanba, E., Mellet, C. O., Garcia Fernandez, J. M., Ohno, K. Molecular basis of 1-deoxygalactonojirimycin arylthiourea binding to human alpha-galactosidase a: pharmacological chaperoning efficacy on Fabry disease mutants. ACS Chem. Biol. 2014, 9(7), pp. 1460-9. (DOI: 10.1021/cb500143h) Kalyoncu, S., Hyun, J., Pai, J. C., Johnson, J.L., Entzminger, K., Jain, A., Heaner, D. P., Morales, I. A., Truskett, T. M., Maynard, J. A., Lieberman, R. L. Effects of protein engineering and rational mutagenesis on crystal lattice of single chain antibody fragments. Proteins: Structure, Function, and Bioinformatics. 2014, 82(9), pp. 1884-95. (DOI: 10.1002/prot.24542) Bethel, C. M., Lieberman, R. L. Protein structure and function: A multimedia-based guided-inquiry education module for the high school science classroom, J. Chem. Educ. 2014, 91(1), pp. 52-55. Hill, S. H., Donegan, R. K., Lieberman, R. L. The glaucoma-associated olfactomedin domain of myocilin forms polymorphic fibrils that are constrained by partial unfolding and peptide sequence. 2013, 426(4), pp. 921-35. (DOI: 10.1016/j.jmb.2013.12.002) Orwig, S. D., Chi, P., Du, Y., Hill, S. E., Cavitt, M.A., Suntharalingam, A. Turnage, K. C., Dickey, C.A., France, S., Fu, H., Lieberman, R. L. Ligands for glaucoma-associated myocilin discovered by a generic binding assay. ACS Chemical Biology. 2013, 9(2), pp. 517-25. (DOI: 10.1021/cb40077766) Lieberman R. L., Peek, M. E., Watkins, J. D. Determination of soluble and membrane protein structures by X-ray crystallography. Methods Mol. Biol. 2013, 955, pp. 475-93. (DOI: 10.1007/978-1-62703-176-9_25) Donegan, R. K., Lieberman, R. L. New direction for glaucoma therapeutics: focus on the olfactomedin domain of myocilin. Future Medicinal Chemistry. 2012, 4(17), pp. 2131-4.(DOI: 10.4155/FMC.12.132) Donegan, R. K., Hill, S. E., Turnage, K. C., Orwig, S. D., Lieberman, R. L. The glaucoma-associated olfactomedin domain of myocilin is a novel calcium-binding protein. J. Biol. Chem. 2012, 287(52), pp. 43370-7. (DOI:10.1074/jbc.M112.408906) Suntharalingam, A. Abisambra, J. F., O'Leary III, J. C. Koren, J., Zhang,B., Joe, M. K., Blair, L. J., Hill, S. E.Jinwal,U. K.,Cockman,M. Duerfeldt, S. F., Tomarev, S.I., Blagg, B. S. J., LIeberman, R. L., Dickey, C.A Grp94 triage of mutant myocilin through ERAD subverts a more efficient a more efficient clearance mechanism. J. Biol. Chem. 2012, 287(48), pp. 40661-9. (DOI:10.1074/jbc.M112.384800) Orwig, S. D., Perry, C. W., Kim, L. Y, Turnage, K. C., Zhang, R., Vollrath, D., Schmidt-Krey, I., Lieberman, R. L., Amyloid fibril formation by the glaucoma-associated olfactomedin domain of myocilin. J. Mol. Biol. 2011, 421(2-3), pp. 242-55. (DOI: 10.1016/j.jmb.2011.12.016) Lieberman, R. L. A guided tour of the structural biology of Gaucher disease: acid-beta-glucosidase and saposin c. Enzyme Research 2011, 2011. (DOI:10.4061/2011/973231) Orwig, S. D., Tan, Y. L., Grimster, N. P., Yu, Z., Powers, E., Kelly, J. W., Lieberman, R. L. Binding of 3,4,5,6-tetrahydroxyazepanes to the acid b glucosidase active site: Implications for pharmacological chaperone design for Gaucher disease. Biochemistry. 2011, 50(49), pp. 10647-57. (DOI:10.1021/bi201619z) Lieberman, R. L. Sneak peak at galactocerebrosidase, Krabbe disease's lysosomal hydrolase. Proc. Natl. Acad. Sci USA. 2011, 108(37), pp. 15017-8. (DOI: 10.1073/pnas.1112653108) Lieberman, R. L., Culver, J. A., Entzminger, K. C., Pai, J. C.; Maynard, J. A. Crystallization chaperone strategies for membrane proteins. Invited review, Methods. 2011, 55(4), pp. 293-302. (DOI:10.1016/j.ymeth.1011.08.004) Burns, J. N., Turnage, K. C. Walker, C. A., Lieberman, R. L. The stability of myocilin olfactomedin domain variants provides new insight into glaucoma as a protein misfolding disorder. Biochemistry. 2011, 50(26), pp. 5824-5833. (DOI:10.1021/bi200231x) Orwig, S. D. and Lieberman, R. L. Biophysical characterization of the olfactomedin domain of myocilin, an extracellular matrix implicated in the inherited form of glaucoma. PLoS One. 2011, 6(1): e16347. (DOI:10.1371/journal.pone.0016347) Pai, J. C.; Culver, J. A.; Drury, J. E.; Lieberman, R. L., Maynard, J. A. Conversion of scFv peptide-binding specificity for crystal chaperone development. Protein Engineering Design and Selection. 2010, 24(5), pp. 419-428. (DOI: 10.1093/protein/gzq120) Burns, J. N.; Orwig, S. D.; Harris, J. L.; Watkins, J. D.; Vollrath, D.; Lieberman, R. L. Rescue of glaucoma-causing mutant myocilin thermal stability by chemical chaperones. ACS Chemical Biology. 2010, 5(5), pp. 477-487. (DOI: 10.1021/cb900282e)