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Our current research interest is in protein modifications by a family of small proteins known as ubiquitin and its homologues. These modifications control life-spans, trafficking, assembly, and enzymatic activities of cellular proteins, and are important in nearly every aspect of biological functions. We employ nuclear magnetic resonance (NMR) and other structural approaches in combination with biochemical, molecular and cellular biological methods to understand these processes at an atomic level. Such knowledge is necessary for developing research and therapeutic approaches to target these processes, in which aberrations are responsible for the development of numerous life-threatening human diseases. Specific areas of interest are outlined below.
Covalent attachments of ubiquitin or its homologues to other proteins are macromolecular chemical reactions that, similar to other macromolecular reactions (e.g., transcription, translation and DNA repair), require several steps catalyzed by multiple enzymes. These processes involve dynamic protein-protein interactions, for which NMR methods are particularly suited and can provide atomic resolution structural information. Knowledge of how macromolecular reactions are catalyzed will lead to improved design of pharmacological intervention strategies, targeting these modifications, for the treatment of a wide variety of human diseases.
Our recent studies have shown that biological consequences of modifications by the ubiquitin-like SUMO protein occur mostly through the interaction between SUMO and a SUMO-binding motif (SBM, also known as SIM). We are currently developing reagents that will inhibit SUMO-mediated protein-protein interactions with specificity for the different SUMO paralogues and different modification forms (monomer or polymer). We are also using such reagents to investigate the role of SUMO-mediated protein-protein interactions in cancer cell sensitivity to DNA damaging chemotherapeutic drugs and radiation, as well as the role of SUMO-mediated protein-protein interactions in the viral life cycle.
Metabolic activity is a reflection of cellular functions. Our laboratory utilizes NMR spectroscopy, in combination with cell biology methods, as tools for metabolomic studies, that is, global analysis of metabolic activities. Our goal is to provide information on cellular pathways and to discover biomarkers for diagnosis, as well as prognosis assessment in cancer therapy.
We are collaborating with several other laboratories with expertise in synthetic chemistry, molecular biology, and medical oncology to develop new therapeutics for cancer. State-of-the-art NMR methods are employed to provide information on protein-ligand interactions at an atomic resolution; information that is critical for the rational design of new therapeutics.
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Weijun Huang, Ph.D.
Staff Scientist
Yi-Jia Li, Ph.D.
NIH NSRA
Postdoctoral Fellow
Vered Marks, Ph.D.
Research Fellow
Ikena Madu, Ph.D.
Research Fellow
Kristen McCue, Ph.D.
Research Fellow
Andrew Namanja, Ph.D.
Research Fellow
Khue Truong
Graduate Student
Loran Colson, B.S.
Research Associate
Steven Wong
Research Associate
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Postdoctoral fellows
Yate-Ching Yuan, Ph.D.
Director of the Bioinformatic Core Facility at the Beckman Research Institute of the City of Hope
Maria Victoria Botuyan, Ph.D.
Staff scientist at Mayo Clinic, MN, USA
Jerry Hu, Ph.D.
Manager, Materials Research Laboratory Spectroscopy Facility, UC Santa Barbara
Donghai Lin, Ph.D.
Professor at Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Suhkmann Kim, Ph.D.
Associate Professor at Pusan National University, Korea.
Sheng Cai, Ph.D.
Director of the NMR laboratory at Marquette University, Wisconsin, USA
Lingyang Zhu, Ph.D.
Senior Scientist, Array BioPharma Inc. Boulder, CO
Thomas Wilkinson, Ph.D.
Staff Scientist, UCLA
Xuanjun Ai, Ph.D.
Postdoctoral fellow with Dr. Charalampos Kalodimos at Rutgers University
Yang Su, Ph.D.
Beijing, China
Jianghai Wang, Ph.D.
Senior Scientist, BostonBiochem, MA, USA
Graduate Students
Ziming Zhang, Ph.D. (2004)
Ziming went to Burnham Institute as a postdoctoral fellow and stayed as Staff Scientist in San Diego Center for Chemical Genomics, Burnham Institute, CA
Jing Song, Ph.D. (2006)
Jing spent two years as a postdoctoral fellow with Professor Timothy Springer at Harvard Medical School, and now is group leader/principal scientist at BioDuro in Beijing.
Research Technician
Qin Liu, M.S., Biomolecular NMR Facility manager, Department of Biochemistry, University of Western Ontario, Canada
Candace Seu, Ph.D. student, UC San Diego
Lisa Fukui, M.D/Ph.D. student, University of Illinois at Urbane Champion
Brian Lee, medical student, SUNY Stony Brook
Larry Tong, medical student, University of Nebraska
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