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Department of Microbiology, A Leader in Microbiology and Microbial Pathogenesis Research and Training.

Immunology and Microbiology
 

Jing Hong Wang, M.D., Ph.D.

Assistant Professor of Immunology & Microbiology


12800 E. 19th Ave., RC1-N 9100
Mail Stop 8333, Aurora, CO 80045

Phone: 303-724-8673
Lab: 303-724-8704
E-mail: jing.wang@ucdenver.edu

Genomic instability and cancer development: Internal or external insults can cause breakages of chromosomes. Incorrect juxtaposition of different pieces of chromosomes during the repair process leads to chromosomal translocation. It is widely accepted that chromosomal translocation can promote cancer development by disrupting tumor suppressors, activating oncogenes, or generating aberrant fusion proteins. Furthermore, cancer type-specific chromosomal translocations are frequently identified in leukemia and lymphomas, and increasingly found in solid tumors. However, many aspects of the mechanisms underlying the generation and cancer-type specificity of chromosomal translocations are poorly understood.  The goal of our laboratory is to understand the molecular mechanisms that promote chromosomal translocations and cancer development in B lymphocytes. Our primary approaches are to establish specific mouse models that resemble human mature B cell lymphomas. In particular, we focus on DNA double strand breaks (DSBs) response factors. These proteins are essential for properly repairing DSBs. In the absence of these factors, DSBs will separate and progress into chromosomal breaks and translocations. We are investigating how these proteins suppress oncogenic translocations. Furthermore, we are elucidating how cancer-type specific translocations are generated at the molecular level, and how mechanistic factors including DSB frequency, spatial proximity of target loci and DNA repair pathways influence translocation frequency and spectrum. We will also employ novel genome-editing approaches (CRISPR-Cas9 system) to test how genetic alterations in DNA repair influence the level of on-going genomic instability in cancer cells.


Molecular mechanism of somatic hypermutation and class switch recombination: More than 90% of human lymphomas are B cell-derived. This is likely because B cells extensively shuffle their genomic DNA during immune responses. Upon immunizations and infections, activated B cells form a specialized structure termed germinal center (GC). In the GC, two B cell-specific DNA alterations occur, namely somatic hypermutation (SHM) and class switch recombination (CSR). Both SHM and CSR rely on the activity of an enzyme called activation induced deaminase (AID). In activated B lymphocytes, AID causes point mutations in the variable regions of the immunoglobulin (Ig) genes. These mutations cause small changes in the protein sequence of antibodies and lead to increased antibody affinity for specific antigens. AID also induces DSBs in the repetitive switch regions that lie upstream of each constant region exon of the Ig heavy chain locus to mediate CSR.  CSR assigns antigen-appropriate effector functions to antibody molecules and is, therefore, a process important for productive immune responses against pathogens.  Eventually AID-mediated DNA alterations enhance antibody diversity and specificity. Given that AID is a potent DNA mutator, its activity has to be tightly regulated. We are interested in elucidating the molecular mechanisms that regulate AID targeting specificity and efficiency. Furthermore, we are also investigating how AID contributes to genomic instability and cancer development. Lastly, we expand our research into the signaling control of CSR process. In particular, we are investigating how antigens and co-stimulatory molecules cooperatively stimulate CSR and elucidating the signaling transduction pathways that promote or inhibit CSR.

Education

2002.9-2004.6

Ph.D. Pathology Program, University of Chicago, Chicago, IL.  Degree was granted in June, 2004.  Thesis Advisor: Dr. Yang-Xin Fu

1996.9-1998.12

Master of Science. Graduate Program in Department of Molecular Genetics, Ohio State University, Columbus, OH. Degree was granted in December, 1998.  Advisor: Dr. Berl Oakley

1991.8-1996.7 

Bachelor of Medicine (equivalent to M.D. in U.S.). Department of Basic Medical Sciences, Beijing Medical University, Beijing, P.R. China. Degree was granted in July, 1996.


Positions

2011.1-present 

Assistant Professor, Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health 

2009.6-2010.12 

Instructor of Pediatrics, Immune Disease Institute, Children’s Hospital Boston, Harvard Medical School. Lab PI: Dr. Frederick W. Alt.

2004.7-2009.6

Postdoctoral Research Fellow, Immune Disease Institute, Children’s Hospital Boston, Harvard Medical School. Lab PI: Dr. Frederick W. Alt.

1999.1-2002.8 

Research Associate, Department of Pathology, University of Chicago.  Lab PI: Dr. Yang-Xin Fu.


Honors/Awards

2014: AAI 2014Early Career Faculty Travel Award

2012: Outstanding Junior Faculty Award, National Jewish Health

2012-present: American Society of Hematology (ASH) Scholar Award

2011-2014: Boettcher Foundation Webb-Waring Early Career Investigator Award

2005-2008: Leukemia and Lymphoma Society (LLS) senior fellowship

1996-1997: Distinguished University Fellowship, Ohio State University

1996: GuangHua Scholarship, Beijing Medical University

Zhangguo Chen, Ph.D.
Assistant Research Professor
Zhangguo.Chen@ucdenver.edu

Xiaomi Chen, Ph.D.
Postdoctoral Fellow
Xiaomi.Chen@ucdenver.edu

Mihret Elos, B.S.
Graduate Student, HMGGP
Mihret.Elos@ucdenver.edu

Postdoctoral fellow position available
Rotation inquiry welcomed