PEOPLE

Craig H. Bassing, PhD

Associate Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine

Contact InformationChildren's Hospital of Philadelphia
4054 Colket Translational Research Building
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 267-426-0311
Fax: 267-426-2791

Specialty Division

Immunobiology and Experimental Pathology

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

Education

B.A. (Biology), The Johns Hopkins University, 1992
Ph.D. (Biology), Duke University, 1997

Specialty Certification

Postgraduate Training

Research Fellow in Medicine, Boston Children's Hospital, 1997-2002
Research Fellow in Genetics, Harvard Medical School, 1997-2002
Research Fellow in Molecular Immunology, CBR Institute for Biomedical Research, 1997-2000
Research Fellow in Molecular Immunology, Irvington Institute for Immunological Research, 1997-2000
Research Associate in Molecular Immunology, Howard Hughes Medical Institute, 2000-2003
Research Fellow in Cancer Genetics , Lymphoma Research Foundation, 2003-2005

Awards and Honors

Alpha Epsilon Delta Honor Society, The Johns Hopkins University Chapter, 1990
Howard Hughes Medical Institute, Summer Fellow, 1991
Phi Beta Kappa Honor Society, The Johns Hopkins University Chapter, 1991
Golden Key Honor Society, The Johns Hopkins University Chapter, 1992
National Science Foundation Pre-Doctoral Fellow Award, 1992-1995
Departmental Honors (Biology), The Johns Hopkins University, 1992
University Honors, The Johns Hopkins University, 1992
Irvington Institute for Immunological Research Fellow Award, 1997-2000
Lymphoma Research Foundation Fellow Award, 2003-2005
American Cancer Society Institutional Research Award, 2005-2006
Pew Scholar in the Biomedical Sciences, 2005-2009
Foerderer-Murray Award, 2005-2006
W.W. Smith Charitable Trust Award, 2005-2007
American Cancer Society Institutional Research Award, 2006-2007
Lassin Family Cancer Research Award at the Abramson Cancer Center of the University School of Medicine, 2008-2009
American Cancer Society Institutional Research Award, 2008
Michael S. Brown New Investigator Research Award, University of Pennsylvania School of Medicine, 2009-2009
Pathology and Laboratory Medicine Chair Award of the Children's Hospital of Philadelphia, 2010
Leukemia and Lymphoma Society Scholar Award, 2010-present

Memberships and Professional Organizations

American Association for the Advancement of Science, 1992 - present
American Association of Immunologists, 2005 - present
Abramson Cancer Center of the Perelman School of Medicine at the University of Pennsylvania, 2005 - present
Irvington Institute for Immunological Research, 2006 - 2006
Cerimon Pharmaceuticals, Inc., 2006 - 2008
National Cancer Institute, 2006 - 2006
American Association for Cancer Research, 2008 - present
Wellcome Trust, 2008 - 2008
UK Cancer Research Project, 2008 - 2008
New York Academy of Sciences, 2009 - present
Special Emphasis Panel/Scientific Review Group 2009/10 ZRG1 OBT-A (58) R Meeting, National Institutes of Health, 2009 - 2009
Center for Childhood Cancer Research, Children's Hospital of Philadelphia Research Institute, 2009 - present
Ad Hoc Reviewer, Cellular and Molecular Immunology B Study Section, Section of Scientific Review, National Institutes of Health, 2009 - 2009
The Henry Kunkel Society, 2010 - present
NIH Study Section ZRG1 IMM-D (02) M - Member Conflict: Myeloid cell Development and Immunoglobulin Repertoire, National Institutes of Health, 2010 - 2010
Israel Science Foundation Grant Program, 2010 - 2010
Austrian Academy of Sciences, Austrian Programme for Advanced Research and Technology, 2010 - 2010
Member, Faculty of 1000, Leukocyte Development Section in the Immunology Faculty, 2012 - present
Special Emphasis Panel/Scientific Review Group 2014/05 ZRG1 IMM-M (80) S meeting, 2014 - 2014
Member, Board of Scientific Counselors, Division of Intramural Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 2014 - present
Ad Hoc Reviewer, Cellular and Molecular Immunology B Study Section, Section of Scientific Review, National Institutes of Health, 2016 - 2016

Web Links


Selected Publications

Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks

Fisher, M.R., Rivera-Reyes, A., Bloch, N.B., Schatz, D.G., Bassing, C.H., The Journal of Immunology [Epub ahead of print](): , 2017

Genomic Alterations of Non-Coding Regions Underlie Human Cancer: Lessons from T-ALL

Rivera-Reyes, A, Hayer, K.E.,. and Bassing, C.H., Trends in Molecular Medicine 12(): 1035-1046, 2016

RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals

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., The Journal of Experimental Medicine 2(): 209-23., 2016

Lymphocyte Lineage- and Developmental Stage-Specific Downregulation of Cyclin D3 in Response to DNA Double Strand Breaks

DeMicco, A., Reich, T., Arya, R., Rivera-Reyes, A., Fisher, M.R., and Bassing C.H., Cell Cycle 21(): :2882-2894, 2016

RAG-mediated DNA double-strand breaks activate a cel type-specific checkpoint to inhibit pre-B cell receptor signals

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., The Journal of Experimental Medicine 213(): 209-223, 2016

Inhibition of precursor B cell malignancy progression by toll-like receptor ligand-induced immune responses

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., Leukemia 10(): 10):2116-2119, 2016, PMID:27220664

Read article

B cell-intrinsic expression of the HuR RNA-binding protein is required for the T cell-dependent immune response in vivo

DeMicco, A., Naradikian, M.S., Sindhava, V.J., Yoon, J-H., Gorospe, M., Wertheim, G.B., Cancro, M.P., and Bassing, C.H., The Journal of Immunology 195(): 3449-3462, 2015

Lineage Specific Contraction of Tcrb Requires a Chromatin Barrier to Protect the Function of a Long-range Tethering Element

Majumder, M., Koues, O.I., Chan, E.A.W., Kyle, K.E., Horowitz, J.E., Yang-Iott, K.S., Bassing, C.H., Taniuchi, I., Krangel, M.S., and Oltz, E.M., The Journal of Experimental Medicine, 2015

Somatic Inactivation of ATM in Hematopoietic Cells Predisposes Mice to Cyclin D3 Dependent T Cell Acute Lymphoblastic Leukemia

Ehlich, L.A., Yang-Iott, K., DeMicco, A., and Bassing, C.H., Cell Cycle 14(): 388-98., 2015

Defining ATM-independent Functions of the Mre11 Complex with a Novel Mouse Model

Balestrini, A., Nicolas, L., Yang-Iott, K., Guryanova, O.A., Levine, R.L., Bassing, C.H., Chaudhuri, J., and Petrini, J.H., Molecular Cancer Research 2(): 185-95, 2015