Ubiquitin-like Modifications
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 a combination of structural, biochemical, molecular and cellular biological methods to understand these processes in cellular regulation and disease pathogenesis, including cancer and HIV replication. Specific areas of interest are outlined below.

The Role of SUMOylation in Oncogenesis
Post-translational modifications by the small ubiquitin-like modifiers (SUMO) are important in oncogenesis and cellular response to DNA damage. Recent findings indicate that the key oncogenic pathways driven by Myc and KRas are dependent on, or addicted to, SUMOylation. For example, knocking down of the gene encoding the catalytic subunit of the SUMO activating enzyme (SAE), SAE2, has the strongest synthetic lethal interaction with Myc hyperactivation. We are investigating the molecular mechanisms underlying the synthetic lethality of SUMOylation with Myc hyperactivation and KRas mutations. In addition, we are investigating the structure-activity relationship of how the inhibitors interact with the SAE and inhibit its enzymatic activity, and use this information to guide further improvement of the inhibitors. These studies could potentially improve treatment of many cancers, as overexpression of Myc is estimated to contribute to 70 percent of all human cancers, and KRas is also frequently mutated in human cancers.

SUMO Modifications and HIV Replication
SUMO-specific proteases (SENP) regulate post-translational modifications by SUMO through catalyzing the maturation of SUMO precursors and the removal of SUMO from modified proteins. Small molecule inhibitors of SENPs that function in cells would be valuable tools for elucidating the functions of SENPs. We have recently identified a family of small molecule inhibitors of SENPs that inhibit de-SUMOylation activities in cells. Coincidently, these small molecules had been shown to confer anti-HIV activities in a National Cancer Institute antiviral screen, although the cellular targets and the mechanism of inhibition of HIV were unknown. We are investigating the molecular mechanism of how SUMOylation is involved in HIV life cycle. In addition, we are conducting the structure-activity relationship studies of how these inhibitors interact with the SENPs and inhibit their enzymatic activity, and use this information to develop improved inhibitors. Furthermore, we are interested in exploiting this pathway to develop a potential strategy for a cure of HIV by allowing the immune system to target HIV infected cells without producing infectious virus.

NMR-based Metabolomics
Metabolic activity is a reflection of cellular functions. Our laboratory utilizes nuclear magnetic resonance (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.

Application of NMR Methods in Drug Discovery
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.

Amanda McMichael
Administrative Assistant

Aileen Alontaga, Ph.D.
Research Fellow

Chih-Hong Chen, Ph.D.
Research Fellow

Li Du, Ph.D.
Research Fellow

Baozong Li, Ph.D.
Research Fellow

Yi-Jia Li, Ph.D.
Staff Scientist

Andrew Namanja, Ph.D.
NIH Career Development Award (K01) Recipient

Eric Samuels
B.S. Graduate Student

Postdoctoral fellows
Yate-Ching Yuan, Ph.D.
Director of the Bioinformatic Core Facility at Beckman Research Institute of 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.
Khue Truong, Ph.D. (2012)
Conducting post doctoral at UCLA.

Research technicians
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
Steven Wong, medical student, UCLA