Craig H. Bassing

faculty photo
Associate Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
4054 Colket Translational Research Building
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 267-426-0311
Fax: 267-426-2791
B.A. (Biology)
The Johns Hopkins University, 1992.
Ph.D. (Biology)
Duke University, 1997.
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Description of Research Expertise

Research Interests:

Elucidation of molecular mechanisms that: 1) mediate the cellular DNA damage response to maintain genomic stability and suppress malignant transformation, and 2) direct the assembly, modification, and silencing of lymphocyte antigen receptor genes to establish adaptive immunity without causing lymphoma or auto-immunity.

Key Words:

DNA repair, genomic instability, cancer, lymphocyte development, V(D)J recombination, class switch recombination, auto-immunity

Research Details:

DNA double strand breaks (DSBs) are hazardous cellular lesions. Unfortunately, they also are very common. DSBs arise in every S phase through DNA replication errors and can be induced in any cell cycle phase by exogenous factors such as ionizing radiation or endogenous factors such as reactive oxygen species. When un-repaired or mis-repaired, DSBs can result in genomic instability that can lead to cell death or drive malignant transformation. Despite their danger, DSBs are a necessary part of biology. In this context, the induction and repair of DSBs within antigen receptor loci during V(D)J recombination and class switch recombination (CSR) is essential for development and function of an immune system capable of adapting and responding to a wide variety of pathogens. Cells have evolved efficient, specialized, and redundant mechanisms to sense, respond to, and repair DSBs. This generally conserved DNA damage response (DDR) integrates cell cycle progression and cellular survival to facilitate repair, or trigger apoptosis if damage is too severe. The physiological importance of V(D)J recombination and CSR control mechanisms has been demonstrated by the fact that defects in each can lead to immunodeficiency, autoimmunity, and lymphoma; while the immunological relevance of DDR control mechanisms has been illustrated by observations that deficiency of these can lead to immunodeficiency and lymphomas with antigen receptor locus translocations. One main research focus within the lab aims to elucidate molecular mechanisms through which the DDR maintains genomic stability and suppresses transformation in cells during V(D)J recombination, CSR, and DNA replication. Another research focus within the lab aims to exploit the knowledge and animal models gained through these studies to design, develop, and test novel treatments for cancer that are more effective and less toxic than current clinical therapies. A third research focus aims to elucidate the epigenetic mechanisms by which antigen receptor gene rearrangements are coordinated between homologous alleles and activated/silenced in a developmental stage-specific manner to maintain genomic stability and suppress cellular transformation during V(D)J recombination. Another research focus within the lab aims to test our hypothesis that the molecular mechanisms that control antigen receptor gene rearrangements and the cellular DDR co-evolved in lymphocytes to ensure development of an effective adaptive immune system without conferring substantial predisposition to autoimmunity or cancer upon the host organism.

Current Lab Personnel:

Katherine Yang-Iott – CHOP Research Associate
Sarah Koniski - CHOP Research Technician
Megan Fisher – UPenn Immunology Graduate Student
Adrian Rivera-Reyes - UPenn Cancer Biology Graduate Student
Glendon Wu – UPenn Immunology Graduate Student
Rahul Arya - CHOP Postdoctoral Fellow

Former Trainees:

PhD Graduate Students

Andrea Carpenter, 2005-2008
Velibor Savic, 2005-2009
Bu Yin, 2006-2010
Marta Rowh, 2006-2010
Brenna Brady, 2007-2011
Natalie Steinel, 2009-2013
Levi Rupp, 2011-2014
Julie Horowitz 2011-2015
Amy DeMicco 2011-2015

Postdoctoral Fellows:

Angella Fusello 2008-2010
Lori Ehrlich 2010-2012

Selected Publications

Arya R and Bassing CH. : V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity. Trends Genetics S0168-9525: 30071-9. 2017.

Fisher, M.R., Rivera-Reyes, A., Bloch, N.B., Schatz, D.G., Bassing, C.H.: Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks. The Journal of Immunology 198: 2943-2956, 2017.

Rivera-Reyes, A, Hayer, K.E.,. and Bassing, C.H.: Genomic Alterations of Non-Coding Regions Underlie Human Cancer: Lessons from T-ALL. Trends in Molecular Medicine 12: 1035-1046, 2016.

Bednarski, J.J., Pandey, R., Schulte, E., White, L.S., Chen, B.R., Sandoval, G.J., Kohyama, M., Haldar, M., Nickless, A., Trott, A., Cheng, G., Murphy, K.M., Bassing, C.H., Payton, J.E., Sleckman, B.P.: RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals. The Journal of Experimental Medicine 2: 209-23. 2016.

DeMicco, A., Reich, T., Arya, R., Rivera-Reyes, A., Fisher, M.R., and Bassing C.H.: Lymphocyte Lineage- and Developmental Stage-Specific Downregulation of Cyclin D3 in Response to DNA Double Strand Breaks. Cell Cycle 21: :2882-2894, 2016.

Bednarski, J.J., Pandey, R., Schulte, W., White, L.S., Chen, B.R., Sandoval, G.J., Kohyama, M., Haldar, M., Nickless, A., Trott, A., Cheng, G., Murphy, K.M., Bassing, C.H., Payton, J.E., and Sleckman, B.P.: RAG-mediated DNA double-strand breaks activate a cel type-specific checkpoint to inhibit pre-B cell receptor signals. The Journal of Experimental Medicine 213: 209-223, 2016.

Fidanza, M., Seif, A.E., DeMicco, A., Rolf, N., Jo, S., Yin, B., Li, Y., Barrett, D.M., Duque-Afonso, J., Cleary, M.L., Bassing, C.H., Grupp, S.A., Reid, G.S.: Inhibition of precursor B cell malignancy progression by toll-like receptor ligand-induced immune responses. Leukemia 10: 10):2116-2119, 2016.

DeMicco, A., Naradikian, M.S., Sindhava, V.J., Yoon, J-H., Gorospe, M., Wertheim, G.B., Cancro, M.P., and Bassing, C.H. : B cell-intrinsic expression of the HuR RNA-binding protein is required for the T cell-dependent immune response in vivo. The Journal of Immunology 195: 3449-3462, 2015.

Ehlich, L.A., Yang-Iott, K., DeMicco, A., and Bassing, C.H. : Somatic Inactivation of ATM in Hematopoietic Cells Predisposes Mice to Cyclin D3 Dependent T Cell Acute Lymphoblastic Leukemia Cell Cycle 14: 388-98. 2015.

Balestrini, A., Nicolas, L., Yang-Iott, K., Guryanova, O.A., Levine, R.L., Bassing, C.H., Chaudhuri, J., and Petrini, J.H. : Defining ATM-independent Functions of the Mre11 Complex with a Novel Mouse Model. Molecular Cancer Research 2: 185-95, 2015.

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Last updated: 06/28/2017
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