Structural Biology; Macromolecular Crystallography; Enzymology; Immune Responses, Rare Disease.
Our laboratory is interested in the relationship of macromolecule three-dimensional structures to biochemical functions. The tools employed are X-ray crystallography, molecular biology, and protein chemistry.
The first research area focuses on enzymatic mechanisms, and mechanisms of protein autoproteolysis and splicing which are posttranslational processing events. We are pursuing structural studies of the autoproteolysis mechanism of glycosylasparaginase, whose mutations in humans result in an inherited lysosomal storage disorder aspartylglycosaminuria (AGU), and the autoproteolysis of a nucleoporin, Nup98, that plays important roles in the nucleocytoplasmic transport of proteins and RNAs.
The second research area is to study enzymes involved in antigen presentation. For an epitope to be recognized by T cells, foreign antigens need to be cut into short peptides with proper sizes in order to form physical complexes with MHC molecules. A few aminopeptidases have recently been identified to play critical roles in trimming peptide precursors and generating the final N-termini of class I-restricted epitopes. We are pursuing structural studies on these critical enzymes.
The other research areas are structural studies of factors interacting with nucleic acids. These include transcription factors, regulatory proteins, reverse transcriptases, as well as restriction enzymes with unique DNA cleavage patterns. The goal is to understand the structural basis for their functions, and specific interactions of protein-protein and protein-nucleic acid, at atomic resolution.
- Other: Structural Biology, (1994), Harvard University - Cambridge, MA
Supporting Area: Molecular Biology
- Ph D: Molecular Biology, (1990), Cornell University - Ithaca, NY
Supporting Area: Chemical Engineering
Dissertation/Thesis Title: Mutational Analysis of Transcriptional Antitermination Mediated by Lambdoid Phage Gene Q Products
- BS: Biochemistry, (1982), National Taiwan University - Taipei, Taiwan
Supporting Area: Chemical Engineering
Dissertation/Thesis Title: Identification of Lentinus edodes by Headspace Analysis
Dr. Hwai-Chen Guo is a Professor in Biological Sciences at UMass Lowell. He received his Ph.D. in Molecular Biology with a minor concentration in Chemical Engineering from Cornell University, and postdoctoral training as a Cancer Research Institute Fellow in Structural Biology at Harvard University. Dr. Guo joined the Department of Biophysics at Boston University School of Medicine as an Assistant Professor in 1994, was appointed Associate Professor in 2001, and subsequently promoted to Full Professor in 2010. He also served as a faculty member of Bioinformatics on the Charles River Campus of Boston University. In 2011, Dr. Guo accepted an offer to join the Department of Biological Sciences at UMass Lowell.
Awards and Honors
- Cancer Research Institute Fellow (1991), Scholarship/Research - Cancer Research Institute
- Damon Runyon-Walter Winchell Cancer Research Fellow (1991), Scholarship/Research - Damon Runyon-Walter Winchell Cancer Research Institute
- Research Associate (1990), Scholarship/Research - Howard Hughes Medical Institute
- Pande, S., Lakshminarasimhan, D., Guo, H. (2017) "Crystal structure of a mutant glycosylasparaginase shedding light on aspartylglycosaminurea-causing mechanism as well as on hydrolysis of non-chitobiose substrate," Mol Genet and Metab 121: pp. 150-156
- Sui, L., Gandhi, A., Guo, H.F. (2016) "Crystal structure of a polypeptide’s C-terminus in complex with the regulatory domain of ER aminopeptidase 1.," Molecular Immunology 80: pp. 41 - 49
- Sui, L., Gandhi, A., Guo, H.F. (2015) "Single-chain expression and crystallization of an antigenic C-terminus in complex with the regulatory domain of ER aminopeptidase 1.," Crystal Structure Theory and Applications 4: pp. 47-52
- Sui, L., Lakshminarasimhan, D., Pande, S., Guo, H. (2014) "Structural basis of a point mutation that causes the genetic disease Aspartylglucosaminuria.," Structure 22: pp. 1855-1861
- Gandhi, A., Lakshminarasimhan, D., Sun, Y., Guo, H.F. (2011) "Structural insights into the molecular ruler mechanism of the endoplasmic reticulum aminopeptidase ERAP1.," Sci. Rep. (Nature Publishing Group) 1: pp. 186 (6 pages)
- Wang, Y., Guo, H.F. (2010) "Crystallographic Snapshot of Glycosylasparaginase Precursor Poised for Autoprocessing.," Journal of Molecular Biology 403: pp. 120-130
- Sun, Y., , Y. (2008) "Structural constraints on autoprocessing of the human nucleoporin Nup98.," Protein Science 17: pp. 494-505
- Wang, Y., Guo, H.F. (2007) "Crystallographic Snapshot of a Productive Glycosylasparaginase-Substrate Complex.," Journal of Molecular Biology 366: pp. 82-92
- Liu, X., Olczak, T., Guo, H.F., Dixon, D.W., Genco, C.A. (2006) "Identification of amino acid residues involved in heme binding and hemoprotein utilization in the Porphyromonas gingivalis heme receptor.," HmuR. Infect. Immun. 74: pp. 1222-1232
- Meyer, R.D., Qian, X., Guo, H.F., Rahimi, N. (2006) "Leucine Motif-dependent Tyrosine Autophosphorylation of Type III Receptor Tyrosine Kinases.," Journal of Biological Chemistry 281:13 pp. 8620-8627
- Meng, J., Vardar, D., Wang, Y., Guo, H.F., Head, J.F., McKnight, C.J. (2005) "High-Resolution Crystal Structures of Villin Headpiece and Mutants with Reduced F-Actin Binding Activity.," Biochemistry 44:36 pp. 11963-11973
- Xu, Q.S., Roberts, R.J., Guo, H.F. (2005) "Two crystal forms of the restriction enzyme MspI-DNA complex show the same novel structure.," Protein Sci. 14: pp. 2590-2600
- Xu, Q.S., Kucera, R.B., Roberts, R.J., Guo, H.F. (2004) "Article: An Asymmetric Complex of Restriction Endonuclease MspI on Its Palindromic DNA Recognition Site.," Structure 12: pp. 1741-1747
- Qian, X., Guan, C., Guo, H.F. (2003) "Article: A Dual Role for an Aspartic Acid in Glycosylasparaginase Autoproteolysis.," Structure 11: pp. 997-1003
- Wang, X., Qian, X., Guo, H.F., Hu, J. (2003) "Heat Shock Protein 90-Independent Activation of Truncated Hepadnavirus Reverse Transcriptase.," Journal of virology 77:8 pp. 4471-4480
- Wang, Y., Guo, H.F. (2003) "Two-step dimerization for autoproteolysis to activate glycosylasparaginase.," J. Biol. Chem. 278: pp. 3210-3219
- Guo, H.F. (2003) "Type II restriction endonucleases: structures and applications.," Recent Research Developments in Macromolecules. S.G. Pandalai , ed. (Trivandrum, India: Research Signpost) pp. 225-245
- O' Loughlin, T.J., Xu, Q., Kucera, R.B., Dorner, L.F., Sweeney, S., Schildkraut, I., Guo, H.F. (2000) "Crystallization and preliminary X-ray diffraction analysis of Mspl restriction endonuclease in complex with its cognate DNA.," Acta Crystallogr. D 56: pp. 1652-1655
- Xu, Q., Buckley, D., Guan, C., Guo, H.F. (1999) "Article: Structural Insights into the Mechanism of Intramolecular Proteolysis.," Cell 98: pp. 651-661
- Cui, T., Liao, P., Guan, C., Guo, H.F. (1999) "Purification and crystallization of precursors and autoprocessed enzymes of Flavobacterium glycosylasparaginase: an N-terminal nucleophile hydrolase.," Acta Crystallogr. D 55: pp. 1961-1964
- Guo, H.F., Xu, Q., Buckley, D., Guan, C. (1998) "Crystal structures of Flavobacterium glycosylasparaginase: an N-terminal nucleophile hydrolase activated by intramolecular proteolysis.," J. Biol. Chem. 273: pp. 20205-20212
- Bouvier, M., Guo, H.F., Smith, K.J., Wiley, D.C. (1998) "Crystal structures of HLA-A*0201 complexed with antigenic peptides with either the amino- or carboxyl-terminal group substituted by a methyl group.," Proteins Struct. Funct. Genet. 33: pp. 97-106
- Guo, H.F., Madden, D.R., Silver, M.L., Jardetzky, T.S., Gorga, J.C., Strominger, J.L., Wiley, D.C. (1993) "Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201 and HLA-B*2705.," Proc. Natl. Acad. Sci. USA 90: pp. 8053-8057
- Silver, M.L., Guo, H.F., Strominger, J.L., Wiley, D.C. (1992) "Atomic structure of a human MHC molecule presenting an influenza virus peptide.," Nature 360: pp. 367-369
- Guo, H.F., Jardetzky, T.S., Garrett, T.P., Lane, W.S., Strominger, J.L., Wiley, D.C. (1992) "Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle.," Nature 360: pp. 364-366
- Guo, H.F., Kainz, M., Roberts, J.W. (1991) "Characterization of the late-gene regulatory region of phage 21.," J. Bacteriology 173: pp. 1554-1560
- Guo, H.F., Roberts, J.W. (1990) "Heterogeneous initiation due to slippage at the bacteriophage 82 late gene promoter in vitro.," Biochemistry 29: pp. 10702-10709
- Goliger, J.A., Yang, X., Guo, H.F., Roberts, J.W. (1989) "Early transcribed sequences affect termination efficiency of Escherichia coli RNA polymerase.," Journal of Molecular Biology 205: pp. 331-341