Rafael C. Casellas, Ph.D.
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine
Present Title & Affiliation
Dual/Joint/Adjunct Appointment
Professor, Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor, Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
Antibody-based immunotherapies are among the most promising treatments against human malignancies. Chimeric antigen receptor (CAR) T cells and T cell engagers efficiently combine tumor antigen recognition by antibody variable domains (heavy and light chains) with T cell cytotoxicity to specifically destroy cancer cells. However, a significant fraction of tumors invariably relapses over time due to antigen loss, mutation or low cell surface density. Targeting multiple antigens simultaneously can in principle solve this problem, but that approach often fails with single chain variable fragments (scFvs) because of cross pairing and aggregation of CARs or the difficulty in assembling large antibody constructs. At the MD Anderson Nanobody Center we seek to overcome these and related hurdles by implementing single chain antibodies (nanobodies) in the development of novel immunotherapies. Through immunization of camelids (the source of natural nanobodies) and the creation of large human nanobody phage libraries we have developed a high-throughput program to rapidly isolate highly specific antibodies against tumor antigens. Our current projects include the production of multimeric CARs against cell surface as well as intracellular (peptide-HLA) targets in hematopoietic and solid tumors.
Education & Training
Degree-Granting Education
| 2002 | Rockefeller University, New York, New York, US, Molecular Immunology, Ph.D |
Postgraduate Training
| 2002-2003 | Research Fellowship, Molecular Biology, California Institute of Technology, Pasadena, California |
Licenses & Certifications
| 2015 | Medical Oncology |
Experience & Service
Administrative Appointments/Responsibilities
Head, Regulome Project, National Institutes of Health, Bethesda, MD, 2010 - 2022
Senior Investigator, Laboratory of Lymphocyte Nuclear Biology, National Institutes of Health, Bethesda, MD, 2004 - 2022
Other Professional Positions
Tenure Track Committee, National Institutes of Health, Bethesda, MD, 2012 - 2016
Regulome Project, National Institutes of Health, Bethesda, MD, 2010 - 2022
Undergraduate Scholarship Program for Minorities, National Institutes of Health, Bethesda, MD, 2010 - 2022
Immunology Interest Group Committee, National Institutes of Health, Bethesda, MD, 2010 - 2012
Honors & Awards
| 2021 | Salzman’s Virology Award, National Institutes of Health |
| 2010 | NIH Director’s Award, National Institutes of Health |
| 2008 | NIH MERIT Award, National Institutes of Health |
| 1996 | Brigham Young University Hypercube Scholar, Brigham Young University |
Professional Memberships
Selected Presentations & Talks
Local Presentations
- 2022. “Why B cells are particularly prone to tumor development”. Conference. “Why B cells are particularly prone to tumor development”. Houston, TX, US.
Formal Peers
- 2022. NCI-NIDDK Seminar Series. Visiting, US.
- 2021. B cell transcriptional regulation and antibody production. Visiting, Melbourne, AU.
- 2021. Laboratory of Immune System Biology. Visiting, US.
- 2021. Nuclear events driving B cell activation and antibody production. Visiting, CT, US.
- 2021. Seminar Series. Visiting. Gaithersburg, Maryland, US.
- 2021. Nuclear architecture regulates transcription and recombination of antibody genes. Visiting, NY, US.
- 2021. NGM Biopharmaceuticals. Visiting. San Francisco, CA, US.
- 2020. Promoter-Enhancer Communication Symposium. Visiting, US.
- 2020. BYU Biochemistry Seminar Series. Visiting. Provo, UT, US.
- 2020. Wall Street, Bridgewater Associates LP. Visiting, NY, US.
- 2019. 4DN Annual Meeting. Visiting. District of Columbia, WA, US.
- 2019. Biowulf Seminar. Visiting, US.
- 2019. NCI Chromosome Biology Symposium. Visiting, US.
- 2019. Biowulf Seminar. Visiting, Shanghai, CN.
- 2019. Nuclear Architecture Conference. Visiting, Beijing, CN.
- 2019. Beijing. Visiting, Beijing, CN.
- 2019. Mediator’s role in transcription and nuclear architecture. Visiting, Maintz, DE.
- 2019. Gordon Research Conference. Visiting, Hong Kong, CN.
- 2019. LCBG Seminar Series. Visiting, US.
- 2019. Epigenetic Regulation (chair). Visiting, US.
- 2018. America Society of Cell Biology. Visiting. San Diego, CA, US.
- 2018. Epigenetics Symposium. Visiting, US.
- 2018. How Nuclear Architecture Regulates Transcription. Visiting. New York, NY, US.
- 2018. Gordon Conference. Visiting, Baeza, ES.
- 2018. ?. Visiting, Warsaw, PL.
- 2018. ?. Visiting. Pasadena, CA, US.
- 2018. ?. Visiting, Paris, FR.
- 2018. ?. Visiting, US.
- 2018. How nuclear architecture and Mediator regulate transcription. Visiting. Philadelphia, PA, US.
- 2018. How nuclear architecture regulates transcription. Visiting, Reykjavik, IS.
- 2018. ?. Visiting, US.
- 2018. ?. Visiting, Helsinki, FI.
- 2018. ?. Visiting, Turku, FI.
- 2018. ?. Visiting. Boston, MA, US.
- 2017. ?. Visiting, CO, US.
- 2017. ?. Visiting, Wuhan, CN.
- 2017. ?. Visiting, Hong Kong, CN.
- 2017. ?. Visiting. Chicago, IL, US.
- 2017. ?. Visiting, US.
- 2017. ?. Visiting, US.
- 2016. Experimental Aspects of Sample Preparation and ChIA-PET Library Construction. Visiting, CT, US.
- 2016. B cell activation triggers Epigenome Amplification and Global Decondensation of Chromatin. Visiting, Kumamoto, JP.
- 2016. ?. Visiting, US.
- 2016. ?. Visiting, PA, US.
- 2016. ?. Visiting, US.
- 2016. ?. Visiting, MD, US.
- 2016. global chromatin acetylation and transcriptome amplification during lymphocyte activation. Visiting, Barcelona, ES.
- 2016. ?. Visiting. Boston, MA, US.
- 2016. The 4D Nucleome Project: Epigenome Amplification in Lymphocytes. Visiting. Bethesda, MD, US.
- 2016. ?. Visiting. Boston, MA, US.
- 2016. ?. Visiting, US.
- 2015. ?. Visiting. Bethesda, MD, US.
- 2015. ?. Visiting, FI.
- 2015. ?. Visiting, CT, US.
- 2015. ?. Visiting. Bethesda, MD, US.
- 2015. ?. Visiting. St. Louis, MO, US.
- 2015. ?. Visiting. Cincinnati, OH, US.
- 2015. ?. Visiting, US.
- 2015. ?. Visiting, Banff, CA.
- 2015. ?. Visiting. New York, NY, US.
- 2015. The NIH Mouse Regulome. Visiting, Jerusalem, US.
- 2015. ?. Visiting, Tel Aviv, IR.
- 2014. ?. Visiting, Hyderabad, IN.
- 2014. ?. Visiting. Houston, TX, US.
- 2014. ?. Visiting, CT, US.
- 2014. ?. Visiting, VA, US.
- 2014. ?. Visiting, Barcelona, ES.
- 2014. ?. Visiting. La Jolla, CA, US.
- 2014. ?. Visiting, Turke, FI.
- 2014. ?. Visiting, Stokholm, SE.
- 2014. ?. Visiting, US.
- 2014. ?. Visiting. Boston, MA, US.
- 2014. ?. Visiting. Provo, UT, US.
- 2013. ?. Visiting. New Haven, CT, US.
- 2013. ?. Visiting, Cordoba, AR.
- 2013. Mechanisms driving B cell tumor-inducing translocations. Visiting, Montevideo, UY.
- 2013. ?. Visiting. East Lansing, MI, US.
- 2013. ?. Visiting, England, GB.
- 2013. ?. Visiting, England, GB.
- 2013. ?. Visiting, Bern, CH.
- 2013. ?. Visiting, US.
- 2013. ?. Visiting, AU.
- 2013. ?. Visiting, Turku, FI.
- 2013. ?. Visiting, Dublin, IE.
- 2013. ?. Visiting, ME, US.
- 2013. Immunity and Tolerance. Visiting, NY, US.
- 2013. ?. Visiting, MD, US.
- 2013. ?. Visiting, US.
- 2013. ?. Visiting, PA, US.
- 2012. ?. Visiting, Melbourne, AU.
- 2012. ?. Visiting, US.
- 2012. ?. Visiting, US.
- 2012. ?. Visiting, AL, US.
- 2012. ?. Visiting, TX, US.
- 2012. ?. Visiting. Bethesda, MD, US.
- 2011. ?. Visiting. New York City, NY, US.
- 2011. Nuclear Contacts and Targeted DNA Breaks Regulate the Frequency of B Cell Chromosome. Visiting. Bethesda, MD, US.
- 2011. ?. Visiting. Los Angeles, CA, US.
- 2011. ?. Visiting, Montreal, CA.
- 2011. ?. Visiting. Chicago, IL, US.
- 2011. Frequency of B Cell Chromosomal Translocations. Visiting. Bethesda, MD, US.
- 2011. Genome Organization and Targeted DNA Damage Determine the Location and Frequency of Chromosomal Translocations. Visiting. Los Angeles, CA, US.
- 2011. ?. Visiting, Barcelona, ES.
- 2011. ?. Visiting, Helsinki, FI.
- 2011. ?. Visiting, Stockholm, SE.
- 2011. ?. Visiting. Washington, DC, US.
- 2011. ?. Visiting, Paris, FR.
- 2011. Genome-wide analysis of AID activity and AID-mediated translocations in B lymphocytes. Visiting, Cambridge, GB.
- 2011. ?. Visiting, London, GB.
- 2011. ?. Visiting, British Columbia, CA.
- 2011. ?. Visiting. Baltimore, MD, US.
- 2011. ?. Visiting, ME, US.
- 2011. ?. Visiting. Boston, MA, US.
- 2010. ?. Visiting. New Haven, CT, US.
- 2010. ?. Visiting, Toronto, CA.
- 2010. ?. Visiting. The Bronx, NY, US.
- 2010. ?. Visiting. Bethesda, MD, US.
- 2010. ?. Visiting, Stokholm, SE.
- 2010. ?. Visiting, PA, US.
- 2009. ?. Visiting, Helsinki, FI.
- 2009. ?. Visiting, Turku, FI.
- 2009. ?. Visiting, Tampere, FI.
- 2009. ?. Visiting, US.
- 2009. Immunity’s microRNome. Visiting, Seoul.
- 2009. ?. Visiting. Bethesda, MD, US.
- 2009. ?. Visiting. Frederick, MD, US.
- 2009. ?. Visiting. St. Louis, MO, US.
- 2009. ?. Visiting. Bethesda, MD, US.
- 2008. ?. Visiting. Bethesda, MD, US.
- 2008. ?. Visiting. Bethesda, MD, US.
- 2008. ?. Visiting, Ligure, IT.
- 2008. ?. Visiting, Paris, FR.
- 2007. ?. Visiting. Baltimore, MD, US.
- 2007. ?. Visiting, OK, US.
- 2007. ?. Visiting, Geneva, CH.
- 2007. ?. Visiting, FI.
- 2007. ?. Visiting. Bethesda, MD, US.
- 2007. ?. Visiting. Baltimore, MD, US.
- 2007. ?. Visiting. Bethesda, MD, US.
- B cell Keystone Symposium. Visiting. Taos, NM, US.
Grant & Contract Support
| Date: | 2024 - 2028 |
| Title: | Cancer Prevention & Research Institute of Texas Multi-Investigator Research Awards |
| Funding Source: | CPRIT MIRA |
| Role: | PI |
Selected Publications
Peer-Reviewed Articles
- Fedkenheuer, M, Shang, Y, Jung, S, Fedkenheuer, K, Park, S, Mazza, D, Sebastian, R, Nagashima, H, Zong, D, Tan, H, Jaiswal, SK, Fu, HQ, Cruz, AC, Vartak, SV, Wisniewski, J, Sartorelli, V, O’Shea, JJ, Elnitski, LL, Nussenzweig, A, Aladjem, MI, Meng, FL, Casellas, RC. A dual role of Cohesin in DNA DSB repair. Nature communications 16(1), 2025. e-Pub 2025. PMID: 39833168.
- Xu, J, Zhou, T, McKee, K, Zhang, B, Liu, C, Nazzari, AF, Pegu, A, Shen, CH, Becker, JE, Bender, MF, Chan, P, Changela, A, Chaudhary, R, Chen, X, Einav, T, Kwon, YD, Lin, BC, Louder, MK, Merriam, JS, Morano, NC, O'Dell, S, Olia, AS, Rawi, R, Roark, RS, Stephens, T, Teng, IT, Tourtellott-Fogt, E, Wang, S, Yang, ES, Shapiro, L, Tsybovsky, Y, Doria-Rose, NA, Casellas, RC, Kwong, PD. Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1. Advanced Science 11(26), 2024. e-Pub 2024. PMID: 38704686.
- Zhao H, Young N, Kalchschmidt J, Lieberman J, El Khattabi L, Casellas R, Asturias FJ. Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core. Nat Commun 12(1):1355, 2021. e-Pub 2021. PMID: 33649303.
- Dai HQ, Et Al, Casellas R, Alt FW. Loop extrusion mediates physiological Igh locus contraction for RAG scanning. Nature 590(7845):338-343, 2021. e-Pub 2021. PMID: 33442057.
- Ba Z, Et Al, Casellas R, Alt FW. CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning. Nature 586(7828):305-310, 2020. e-Pub 2020. PMID: 32717742.
- Zhang X, Et Al, Casellas R. Fundamental roles of chromatin loop extrusion in antibody class switching. Nature 575(7782):385-389, 2019. e-Pub 2019. PMID: 31666703.
- Petermann F, Et Al, Casellas, R, O'Shea, J.J. The Magnitude of IFN-gamma Responses Is Fine-Tuned by DNA Architecture and the Non-coding Transcript of Ifng-as1. Mol Cell 75(6):1229-1242.e5, 2019. e-Pub 2019. PMID: 31377117.
- El Khattabi L, Et Al, Casellas, R. A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers. Cell 178(5):1145-1158.e20, 2019. e-Pub 2019. PMID: 31402173.
- Delgado-Benito V, Et Al, Casellas R, Di Virgilio M. The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination. Mol Cell 72(4):636-649.e8, 2018. e-Pub 2018. PMID: 30293785.
- Shastri N, Et Al, Casellas R, Brown EJ. Genome-wide Identification of Structure-Forming Repeats as Principal Sites of Fork Collapse upon ATR Inhibition. Mol Cell 72(2):222-238.e11, 2018. e-Pub 2018. PMID: 30293786.
- Vian L, Et Al, Casellas R. The Energetics and Physiological Impact of Cohesin Extrusion. Cell 175(1):292-294, 2018. e-Pub 2018. PMID: 30241609.
- Vian L, Et Al, Casellas R. The Energetics and Physiological Impact of Cohesin Extrusion. Cell 173(5):1165-1178.e20, 2018. e-Pub 2018. PMID: 29706548.
- Li G, Et Al, Casellas R, Baltimore D. Epigenetic silencing of miR-125b is required for normal B-cell development. Blood 131(17):1920-1930, 2018. e-Pub 2018. PMID: 29555645.
- Rao SSP, Et Al, Casellas R, Aiden EL. Cohesin Loss Eliminates All Loop Domains. Cell 171(2):305-320.e24, 2017. e-Pub 2017. PMID: 28985562.
- Kieffer-Kwon KR, Et Al, Casellas R. Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation. Mol Cell 67(4):566-578.e10, 2017. e-Pub 2017. PMID: 28803781.
- Canela A, Et Al, Casellas R, Nussenzweig A. Genome Organization Drives Chromosome Fragility. Cell 170(3):507-521.e18, 2017. e-Pub 2017. PMID: 28735753.
- Wang Q, Et Al, Casellas R, Robbiani DF. The cell cycle restricts activation-induced cytidine deaminase activity to early G1. J Exp Med 214(1):49-58, 2017. e-Pub 2017. PMID: 27998928.
- Cruz AC, Et Al, Casellas R, Siegel RM. Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction. Nat Commun 7:13895, 2016. e-Pub 2016. PMID: 28008916.
- Zhang S, Et Al, Casellas R, Bustin M. HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells. Nucleic Acids Res 44(15):7144-58, 2016. e-Pub 2016. PMID: 27112571.
- Swaminathan S, Et Al, Casellas R, Muschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol 16(7):766-774, 2015. e-Pub 2015. PMID: 25985233.
- Pratama A, Et Al, Casellas R, Vinuesa CG. MicroRNA-146a regulates ICOS-ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres. Nat Commun 6:6436, 2015. e-Pub 2015. PMID: 25743066.
- Meng FL, Et Al, Casellas R, Alt FW. Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell 159(7):1538-48, 2014. e-Pub 2014. PMID: 25483776.
- Qian J, Et Al, Casellas R. B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity. Cell 159(7):1524-37, 2014. e-Pub 2014. PMID: 25483777.
- Kieffer-Kwon KR, Et Al, Casellas R. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell 155(7):1507-20, 2013. e-Pub 2013. PMID: 24360274.
- Kouzine F, Et Al, Casellas R. Global regulation of promoter melting in naive lymphocytes. Cell 153(5):988-99, 2013. e-Pub 2013. PMID: 23706737.
- Jankovic M, Et Al, Casellas R, Nussenzweig MC. 53BP1 alters the landscape of DNA rearrangements and suppresses AID-induced B cell lymphoma. Mol Cell 49(4):623-31, 2013. e-Pub 2013. PMID: 23290917.
- Di Virgilio M, Et Al, Casellas R, Nussenzweig A. Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339(6120):711-5, 2013. e-Pub 2013. PMID: 23306439.
- Bothmer A, Et Al, Casellas R, Robbiani DF. Mechanism of DNA resection during intrachromosomal recombination and immunoglobulin class switching. J Exp Med 210(1):115-23, 2013. e-Pub 2013. PMID: 23254285.
- Nie Z, Et Al, Casellas R, Levens D. c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell 151(1):68-79, 2012. e-Pub 2012. PMID: 23021216.
- Meredith MM, Et Al, Casellas R, Nussenzweig MC. Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. J Exp Med 209(9):1583-93, 2012. e-Pub 2012. PMID: 22851594.
- Baba M, Et Al, Casellas, R. The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development. Blood 120(6):1254-61, 2012. e-Pub 2012. PMID: 22709692.
- Takahashi H, Et Al, Casellas R, O'Shea JJ. TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol 13(6):587-95, 2012. e-Pub 2012. PMID: 22544395.
- Hakim O, Et Al, Casellas R. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 484(7392):69-74, 2012. e-Pub 2012. PMID: 22314321.
- Fritz JH, Rojas OL, Simard N, McCarthy DD, Hapfelmeier S, Rubino S, Robertson SJ, Larijani M, Gosselin J, Ivanov II, Martin A, Casellas R, Philpott DJ, Girardin SE, McCoy KD, Macpherson AJ, Paige CJ, Gommerman JL. Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut. Nature 481(7380):199-203, 2011. e-Pub 2011. PMID: 22158124.
- Klein IA, Et Al, Casellas R, Nussenzweig MC. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147(1):95-106, 2011. e-Pub 2011. PMID: 21962510.
- Yamane A, Et Al, Casellas R. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat Immunol 12(1):62-9, 2011. e-Pub 2011. PMID: 21113164.
- Pavri R, Et Al, Casellas R, Nussenzweig MC. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143(1):122-33, 2010. e-Pub 2010. PMID: 20887897.
- Daniel JA, Et Al, Casellas R, Nussenzweig A. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science 329(5994):917-23, 2010. e-Pub 2010. PMID: 20671152.
- Kuchen S, Et Al, Casellas R. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity 32(6):828-39, 2010. e-Pub 2010. PMID: 20605486.
- Ji Y, Et Al, Casellas R, Schatz D. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141(3):419-31, 2010. e-Pub 2010. PMID: 20398922.
- Klemm L, Et Al, Casellas R, Müschen M. The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 16(3):232-45, 2009. e-Pub 2009. PMID: 19732723.
- Takizawa M, Et Al, Casellas R. AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development. J Exp Med 205(9):1949-57, 2008. e-Pub 2008. PMID: 18678733.
- Teng G, Et Al, Casellas R, Papavasiliou FN. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28(5):621-9, 2008. e-Pub 2008. PMID: 18450484.
- Kruhlak M, Et Al, Casellas R. The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks. Nature 447(7145):730-4, 2007. e-Pub 2007. PMID: 17554310.
Review Articles
- Casellas R, Et Al. Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity. Nat Rev Immunol 16(3):164-76, 2016. e-Pub 2016. PMID: 26898111.
- Aiden EL, Casellas R. Somatic Rearrangement in B Cells: It's (Mostly) Nuclear Physics. Cell 162(4):708-11, 2015. e-Pub 2015. PMID: 26276627.
- Barlow JH, Et Al, Casellas R, Nussenzweig A. Identification of early replicating fragile sites that contribute to genome instability. Cell 152(3):620-32, 2013. e-Pub 2013. PMID: 23352430.
Other Articles
- Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Muschen M Author Correction: Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol, 2025. PMID: 41315083.
Patient Reviews
CV information above last modified July 22, 2026