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
Education:
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 IGG Graduate Student
Amy DeMicco – UPenn CAMB Graduate Student
Julie Horowitz – UPenn IGG Graduate Student


Former Trainees:

Graduate Students

Andrea Carpenter, 2005-2008, Ph.D. 2008
Velibor Savic, 2005-2009, Ph.D. 2009
Bu Yin, 2006-2010, Ph.D. 2010
Marta Rowh, 2006-2010, Ph.D. 2010
Brenna Brady, 2007-2011, Ph.D. 2011
Natalie Steinel, 2009-2013, Ph.D. 2013
Levi Rupp, 2011-2014, Ph.D. 2014

Fellows:

Angella Fusello PhD, 2008-2010
Lori Ehrlich MD/PhD, 2010-2012

Selected Publications

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 Cancer Research Under Revision, 2014.

Sandoval, G., Graham, D., Gmyrek, G., Akilesh, H., Fujikawa, K., Sammut, B., Bhattacharya, D., Srivatsan, S., Kim, A., Shaw, A., Yang-Iott, K., Bassing, C., Duncavage, E., Xavier, R., Swat, W.: Novel Mechanism of Tumor Suppression by Polarity Gene Discs Large 1 (DLG1) Revealed in a Murine Model of Pediatric B-ALL. Cancer Immunology Research In Press, 2014.

Vaites, L.P., Lian, Z., Yin, B., DeMicco, A., Bassing, C.H., and Diehl, J.A.: ATM deficiency augments constitutively nuclear cyclin D1-driven genomic instability and lymphomagenesis. Oncogene 33: 129-33, 2014.

Ruppa L.J., Chen, L., Krangel, M.S., and Bassing, C.H.: Molecular Analysis of Mouse T Cell Receptor α and β Gene Rearrangements Methods in Molecular Biology In Press, 2014.

Bednarski, J.J., Pandey, R., Sandoval, G.J., Haldar, M., Schulte, E., Nickless, A., White, L., Trott, A., Cheng, G., Schreiber, R.D., Murphy, K.M., Bassing, C.H., Payton, J.E., and Sleckman, B.P.: DNA Damage Responses Triggered by RAG DNA Double Strand Breaks Attenuate Pre-BCR Signaling Through Sequential Activation of ATM, NF-kB2, and SPIC. Nature Immunology Under Review, 2014.

Horowitz, J.E. and Bassing, C.H.: NonCore RAG1 Regions Promote Vβ Rearrangements and αβ T Cell Development by Overcoming Inherent Inefficiency of Vβ Recombination Signal Sequences Journal of Immunology Jan 10. [Epub ahead of print], 2014.

Steinel, N.C., Fisher, M., Yang-Iott, K.S., and Bassing, C.H.: The Ataxia Telangiectasia Mutated and Cyclin D3 Proteins Cooperate to Enforce Tcrb and Igh Allelic Exclusion. Journal of Immunology In Press, 2014.

Rupp, L.J., Brady, B.L., Carpenter, A.C., De Obaldia, M.E., Bhandoola, A., Bosselut, R., Muljo, S.A., and Bassing, C.H.: The microRNA biogenesis machinery modulates lineage commitment during αβ T cell development The Journal of Immunology In Press, 2014.

Ehrlich, L.A., Yang-Iott, K., and Bassing, C.H. : Tcrδ Translocations that Delete the Bcl11b Haploinsufficient Tumor Suppressor Gene Promote Atm-deficient T Cell Acute Lymphoblastic Leukemia Cell Cycle In Press, 2014.

Brady, B.L., Rupp, L.J., and Bassing, C.H.: Requirement for Dicer in Survival of Proliferating Thymocytes Experiencing DNA Double Strand Breaks Journal of Immunology 190: 3256-66, 2013.

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Last updated: 09/08/2014
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