Laboratory of Molecular Immunogenetics

Rafael Casellas, Ph.D.
Chief, Laboratory of Molecular Immunogenetics
Phone: (301) 402-7858
Fax: (301) 402-7110
E-mail: casellar@mail.nih.gov

Autoimmune and other inflammatory diseases result from dysfunctions in the regulation of the immune system. The focus of the Laboratory of Molecular Immunogenetics (LMI) is towards understanding the genetic and molecular regulation involved in normal and abnormal immune cell processes and how these events control immune system regulation and disease. The LMI studies the role of key immune genes in controlling immunoglobulin class switching, DNA repair, immune cell activation, recruitment and function, and regulation of gene expression. Understanding the molecular underpinning on how inflammation is regulated in both health and disease is essential for developing targeted therapeutic agents that can ameliorate immune system disorders with minimal side effects.

The LMI uses a multidisciplinary investigative approach that includes biochemistry, cell biology, immunology, molecular biology, and genetics to explore this problem. The Laboratory also employs cutting edge technologies to facilitate discoveries.The coupling of a multidisciplinary approach with innovative technologies provides a fertile ground for scientific discovery and training.


Selected Publications

Kieffer-Kwon KR, Tang Z, Mathe E, Qian J, Sung MH, Li G, Resch W, Baek S, Pruett N, Grøntved L, Vian L, Nelson S, Zare H, Hakim O, Reyon D, Yamane A, Nakahashi H, Kovalchuk AL, Zou J, Joung JK, Sartorelli V, Wei CL, Ruan X, Hager GL, Ruan Y, Casellas R. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell. 2013 Dec 19;155(7):1507-20. doi: 10.1016/j.cell.2013.11.039. PubMed Icon

Kouzine F, Wojtowicz D, Yamane A, Resch W, Kieffer-Kwon KR, Bandle R, Nelson S, Nakahashi H, Awasthi P, Feigenbaum L, Menoni H, Hoeijmakers J, Vermeulen W, Ge H, Przytycka TM, Levens D, Casellas R. Global regulation of promoter melting in naive lymphocytes. Cell. 2013 May 23;153(5):988-99. doi: 10.1016/j.cell.2013.04.033. PubMed Icon

Nakahashi H, Kwon KR, Resch W, Vian L, Dose M, Stavreva D, Hakim O, Pruett N, Nelson S, Yamane A, Qian J, Dubois W, Welsh S, Phair RD, Pugh BF, Lobanenkov V, Hager GL, Casellas R. A Genome-wide Map of CTCF Multivalency Redefines the CTCF Code. Cell Rep. 2013 May 22. pii: S2211-1247(13)00206-4. doi: 10.1016/j.celrep.2013.04.024. [Epub ahead of print] PubMed Icon

Yamane A, Robbiani DF, Resch W, Bothmer A, Nakahashi H, Oliveira T, Rommel PC, Brown EJ, Nussenzweig A, Nussenzweig MC, Casellas R. RPA Accumulation during Class Switch Recombination Represents 5'-3' DNA-End Resection during the S-G2/M Phase of the Cell Cycle. Cell Rep. 2013 Jan 1. pii: S2211-1247(12)00431-7. doi: 10.1016/j.celrep.2012.12.006. PubMed Icon

Jankovic M, Feldhahn N, Oliveira TY, Silva IT, Kieffer-Kwon KR, Yamane A, Resch W, Klein I, Robbiani DF, Casellas R, Nussenzweig MC. 53BP1 Alters the Landscape of DNA Rearrangements and Suppresses AID-Induced B Cell Lymphoma. Mol Cell. 2013 Jan 1. pii: S1097-2765(12)00988-4. doi: 10.1016/j.molcel.2012.11.029. PubMed Icon

Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell. 2011 Sep 30;147(1):95-106. PubMed Icon

Yamane A, Resch W, Kuo N, Kuchen S, Li Z, Sun HW, Robbiani DF, McBride K, Nussenzweig MC, Casellas R. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nature Immunology 2011 Jan;12(1):62-9. PubMed Icon

Pavri R, Gazumyan A, Jankovic M, Di Virgilio M, Klein I, Ansarah-Sobrinho C, Resch W, Yamane A, Reina San-Martin B, Barreto V, Nieland TJ, Root DE, Casellas R, Nussenzweig MC. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 2010 Oct 1;143(1):122-33. PubMed Icon

Kuchen S, Resch W, Yamane A, Kuo N, Li Z, Chakraborty T, Wei L, Laurence A, Yasuda T, Peng S, Hu-Li J, Lu K, Dubois W, Kitamura Y, Charles N, Sun HW, Muljo S, Schwartzberg PL, Paul WE, O'Shea J, Rajewsky K, Casellas R. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity. 2010 Jun 25;32(6):828-39. PubMed Icon

Ji Y, Resch W, Corbett E, Yamane A, Casellas R*, Schatz DG*. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell. 2010 Apr 30;141(3):419-31. PubMed Icon

See extended list of publications

 

Updated January 8, 2014