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YUNG CHANG Associate Professor Ph.D., University of Iowa Send e-mail to yung.chang@asu.edu

Research

My primary interest lies in understanding the mechanisms in V(D)J recombination joining process. Developing lymphocytes have the unique ability to generate a vast diversity of antigen receptor molecules, immunoglobulins and T cell receptors. The assembly of these receptor genes is achieved through site-specific recombination events from separately encoded gene segments, variable (V), diversity (D) and joining (J) regions, known as V(D)J recombination. This process consists two distinct steps: a site-specific cleavage to generate double strand DNA breaks and a ubiquitous joining of these breaks. Defects in this recombination process could lead to immune deficiency and possible lymphoid malignancy.

Our research effort is directed in several areas: 1) to study the underlying mechanism of V(D)J recombination joining process; 2) to investigate the effect of V(D)J recombination on lymphocyte development; 3) to examine the pathogenic impact of defective V(D)J recombination on malignant transformation of lymphocytes. Finally, based on our recent finding in the zebrafish recombination process, we combine experimental and bioinformatics approaches to explore origination and evolution of V(D)J recombination. Knowledge generated from these studies may provide clues to the understanding of normal lymphopoiesis, immunodeficiency, and oncogenesis of lymphoid system.

Current Students

Danny Franco, Ph.D., Molecular & Cellular Biology

David Wilson, Ph.D., Microbiology

Jeffrey Pavlicek, PhD, Microbiology

Stephanie Rogers, M.S. Molecular & Cellular Biology

Sarah Salameh, M.S. Bioengineering

Selected Publications

Zhong, H., Z. Li, S. Lin and Y. Chang. 2006. Initiation of V(D)J recombination in zebrafish (Danio rerio) ovaries. Mol. Immunol. In press.

Li, Z., Y. Chang. 2006. V(D)J recombination in zebrafish: normal joining products with accumulation of unresolved coding ends and deleted signal ends. Mol. Immunol. In press.

Bogani, F. E. McConnell, L. Joshi, Y. Chang, G. Ghirlanda. 2006. A designed glycoprotein analogue of Gc-MAF exhibits native-like phagocytic activity. J. Am. Chem. Soc. 128:7142-7143.

Jacobsen, E. O. Ananieva, M. L. Brown and Y. Chang. 2006. Growth, differentiation and malignant transformation of pre-B cells mediated by inducible activation of v-Abl oncogene. J. Immunol. 176: 6831-6838.

Chen, Y., T. Fu. T. Tao, J. Yang, Y. Chang, M. Wang, L. Kim, L. Qu, J. Cassady, R. Scalzo & X. Wang. 2005. J. Nat. Prod. 68: 773-776.

Jacobson, E., T. Beach, Y. Shen, R. Li, & Y. Chang. 2004. Reduction of the Mre11 DNA repair complex in Alzheimer's Diseases. Mol. Brain Res. 128:1-7

Pettit, G. R., H. Hoffman, H. D. L Herald, P. M. Blumberg, E. Hamel, J. M. Schmidt, Y. Chang, R. K. Pettit, N. E. Lewin and L. V. Pearce. 2004. Antineoplastic agents. 499. Synthesis of hystatin 2 and related 1H-benzo[de][1,6]-naphthyridinium salts from aaptamine. J. Med. Chem. 47: 1775-1782.

Martina, C., A. Bell, J. Wayne and Y. Chang. 2003. In vivo ligation of CD3 on neonatal scid thymocytes blocks g-irradiation-induced TCRb rearrangements and thymic lymphomagensis. Immunol. Letter. 85: 279-286.

Middlebrook AJ, C. Martina, Y. Chang, R. J. Lukas & D. DeLuca. 2002. Effects of nicotine exposure on T cell development in fetal thymus organ culture: arrest of T cell maturation. J Immunol. 169:2915-2924.

Brown, M. L., D. Franco, A. Brkel and Y. Chang. 2002. Role of PARP in DNA- PK independent recombination. PNAS 98:4532-4537.

Perkins, E. J., A. Nair, D. O. Cowley, T. Van Dyke, Y. Chang and D. A. Ramsden. 2002. Sensing of intermediates in V(D)J recombination by ATM. Genes & Dev. 16:159-164.

Brown, M. L., S. Lew and Y. Chang. 2000. The scid recombination-inducible cell line: a model to study DNA-PK-independent V(D)J recombination. Immunol. Letter. 75: 21

Lew, S., D. Franco and Y. Chang. 2000. Activation of V(D)J recombination induces the formation of interlocus joints and hybrid joints in scid pre-B cell lines. Mol. Cell. Biol. 20(19):7170-7.

Brown, M. L and Y. Chang. 2000. Metabolism of recombination coding ends in scid cells. J. Immunol. 164:4135-4142.

Bosma, G.C., Y. Chang, and M. J. Bosma, 1999. Differential effect of an immunoglobulin m transgene on development of pre-B cells in fetal and adult scid mice. PNAS 96:11952-11957.

Chang, Y., M. J. Bosma, and G. C. Bosma. 1999. Extended duration of DH-JH rearrangement in immunoglobulin heavy chain transgenic mice: implications for regulation of allelic exclusion. J. Exp. Med. 189: 1295-1305.

Chang, Y., and Brown, M. L. 1999. Formation of coding joints in V(D)J recombination-inducible scid pre-B cell lines. PNAS 96: 191-196

Chang, Y. and M. J. Bosma. 1997. Immunoglobulin transgenic scid mice: requirements for the rescue of scid B cell differentiation. Int. Immunol. 9:373-380.

Chang, Y., G. C. Bosma and M. J. Bosma. 1995. Development of B cells in scid mice with immunoglobulin transgenes: Implications for the control of VDJ recombination. Immunity 2: 607-616.