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Immunology and Microbial Science

Changchun Xiao, Ph.D.

Associate Professor
Department of Immunology and Microbial Science
California Campus
Laboratory Website
cxiao@scripps.edu
(858) 784-7640

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

The primary focus of our research is to understand the functions of microRNA control and its underlying molecular mechanisms in the mammalian immune system, under health and disease conditions.

MicroRNAs have recently emerged as important factors in the post-transcriptional control of cellular protein concentrations in metazoan organisms. These ~22 nucleotide RNAs pair with mRNAs of protein coding genes to specify their translational repression or degradation. MicroRNAs display distinct temporal and spatial expression patterns and regulate a diverse range of cellular processes, including cell differentiation, proliferation, and apoptosis. Emerging evidence suggests that they can be involved in the control of lymphocyte development and function, as well as lymphomagenesis. However, the specific functions, expression regulation, and molecular mechanisms of action of individual microRNAs remain largely unknown.

We identified a few lymphocyte-specific microRNAs by expression profiling and investigated their functions by generating and analyzing mice with loss- and gain-of-function mutation. We have found that miR-150 controls c-Myb expression and regulates B cell development and response. We also discovered that another microRNA, miR-17~92, contributes to lymphomagenesis by downregulating the protein levels of Pten and Bim. The mice with elevated miR-17~92 expression in their lymphocytes developed lymphoproliferative disease, autoimmunity, and died prematurely.

Based on studies from us and other investigators, some key features of microRNA control have been revealed: (1) a dose-dependent regulation of protein concentrations of target genes over a mostly modest range; (2) subtle changes of concentrations of some key cellular proteins can have profound physiological effects as documented by the many pathologies arising from haploinsufficiency; (3) targeting of several components of a functional network may further enhance the functional impact of microRNA control. A major challenge in the field is to identify the critical targets of individual microRNAs and the molecular pathways they regulate in a given biological context.

We are employing genetic, genomic, proteomic, biochemical, and bioinformatics approaches to understand the functions and molecular mechanisms of microRNA control at molecular, cellular, and system levels, in the context of lymphocyte differentiation, lymphomagenesis and autoimmune diseases. These experimental approaches can also be used to study microRNAs in other systems, when opportunities emerge.

Education

B.S., Biology, Tsinghua University, 1995
M.S., Immunobiology, Yale University, 1998
Ph.D., Immunobiology, Yale University, 2002

Awards & Professional Activities

2010 Pew Scholar in Biomedical Sciences
2009 Cancer Research Institute Investigator Award

Selected References

Xiao C and Rajewsky K. (2009) MicroRNA Control in the Immune System: Basic Principles. Cell 136: 26-36.

Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K. (2008) Lymphoproliferative disease and autoimmunity in mice with elevated miR-17-92 expression in lymphocytes. Nature Immunology 9:405-14.

Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K. (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131: 146-59

Monticelli S, Ansel KM, Xiao C, Socci ND, Krichevsky AM, Thai TH, Rajewsky N, Marks DS, Sander C, Rajewsky K, Rao A, Kosik KS. (2005) MicroRNA profiling of the murine hematopoietic system. Genome Biology 6(8): R71

Links

Xiao Lab Website

Immunology and Microbial Science Home
IMS - California
IMS - Florida
Department Contacts
Links
Affinity Group
IMS Research Forum (Scripps Researchers Only)
NIH Postdoctoral Training Grant
Breakfast Club Meeting

Faculty

Andersen, Kristian
Baccala, Roberto
Burton, Dennis
Chisari, Frank
Choe, Hyeryun
Cochrane, Charles
Dai, Yang D
de la Torre, Juan C.
DerMardirossian, Celine
Edgington, Thomas S.
Elder, John
Farzan, Michael
Feeney, Ann
Franc, Nathalie
Gallay, Philippe
Garaigorta De Dios, Urtzi
Gavin, Amanda
Hangartner, Lars
Havran, Wendy
Kang, Young Jun
Kim, Dae Hee
Kirak, Oktay
Kono, Dwight
Kravchenko, Vladimir
Lasmezas, Corinne
Law, Mansun
Lawson, Brian
McHeyzer-Williams, Michael
Mosier, Donald
Nemazee, David
Nemerow, Glen
Oldstone, Michael B.A.
Petrie, Howard
Reisfeld, Ralph
Ruf, Wolfram
Saphire, Andrew
Saphire, Erica Ollmann
Sauer, Karsten
Schief, William
Sherman, Linda
Song, Byeong Doo
Sullivan, Brian
Teijaro, John
Tellinghuisen, Timothy
Teyton, Luc
Theofilopoulos, Argyrios
Ulevitch, Richard
Valente, Susana Tereno
Weissmann, Charles
Whitton, J. Lindsay
Wyatt, Richard
Xiao, Changchun
Zhu, Jiang
Zwick, Michael

Affiliated Faculty

Getzoff, Elizabeth
Janda, Kim
Kaufmann, Gunnar Joerg F
Paulson, James C.
Torbett, Bruce

Adjunct Faculty

Dennis, Edward
Ditzel, Henrik
Feuer, Ralph
Gascoigne, Nicholas
Ghazal, Peter
Guidotti, Luca
Han, Jiahuai
Isogawa, Masanori
Knaus, Ulla
Mackman, Nigel
Jameson, Julie
McGavern, Dorian
McKay, Dianne
Merson, James
Poignard, Pascal
Sette, Allessandro
Sigurdson, Christina
Surh, Charles