Contact

Location: MED 5.007V

Department

Microbiology, Immunology & Molecular Genetics

Casali, Paolo, M.D.

UT Ashbel Smith Professor and Distinguished Research Professor

Personal Statement:

Dr. Casali’s research focuses on epigenetic mechanisms regulating expression of the immunoglobulin locus, as well as genome-wide and specific gene expression in antibody and autoantibody responses and immune B cell memory.  Experimental approaches include cutting-edge molecular genetic methods, in vitro immune cell cultures, in vivo models of immunity and autoimmunity, with emphasis on humanized mice (H-Mice) recently developed in Dr. Casali lab and as adapted to vaccine development and autoimmunity.

Education

  • M.D., University of Milan, School of Medicine & Surgery, 1974
  • University of Milan, School of Medicine & Surgery, Specialty Diploma and Board Certification in Allergy and Clinical Immunology, 1976
  • University of Milan, School of Medicine & Surgery, Specialty Diploma and Board Certification in Microbiology and Virology, 1984

Research

Knowledge in the biological and biomedical sciences continues to accelerate at a remarkably rapid pace. All of us are witnessing this extraordinary scientific revolution and almost endless application of today’s discoveries and modern technologies to improve tomorrow’s lifestyles and societal well-being. Recent observations concerning the influence of the microbiome on human health and disease further reinforce the fundamental contributions and influence of microorganisms on immunity, inflammation, nutrition, metabolic integrity, and neurological development. Therefore, a graduate focus in Microbiology and Immunology offers many exciting opportunities to become the multitalented, innovative and interdisciplinary scientist and educator required to compete in today’s evolving scientific world. Our graduate program emphasizes interactive and self-directed courses in microbiology and immunology as well as meaningful exposure to other biomedical disciplines, which provides the appropriate and relevant intellectual balance and preparation. Advanced courses in many key areas of Microbiology and Immunology are available, so that students can build upon their expanding knowledge base. Furthermore, students learn to write and critique grant proposals, develop skills in communication, and discuss the ethical basis of scientific research and conduct. Thus, our responsibility to graduate students in the Microbiology and Immunology Program is to provide focused yet sufficiently broad educational and research experiences, so that each student encounters and utilizes state-of-the-art approaches to further their investigative talents and research explorations. This commitment will enable trainees to prepare for the range of exciting career choices that await them in the fields of academia, biotechnology, government, and numerous other cross-over professional specialties.

Publications

(selected publications since 2000) Complete List of Publications

  • Chupp, D.P., C.E. Rivera, Y. A. Fisher, H. Zan and P. Casali.  2022. Construction of mice with a fully human immune system mounting class-switched, hypermutated and neutralizing antibody responses.  Cell, to be submitted.
  • Rivera, C.E., Y. Zhou, A.D. Fisher, D.P. Chupp, H. Yan, J.R. Simon, H. Zan, Z. Xu and P. Casali.  2022.  T-independent TLR-BCR linked coengagement induces class-switched, hypermutated and neutralizing antibody responses.  Science Immunol., submitted.
  • Yan, H., R. Wang, M. Fernandez, C. E. Rivera, C. Cervantes, J.B. Moroney, X.-D. Li, N. Zhang, X.-Z. Meng, Z. Yin, R. Kedl, B. Min, C.A. Hunter, Y. Xiang, P. Casali and Z. Xu.  2022.  BATF3-dependent induction of IL-27 by B cells bridges the innate and adaptive stages of the antibody response. bioRxiv 2020 Jun; doi. 10.1101/2020.06.26.117010. To be submitted to Cell.
  • Xu, Y., H. Zhou, G. Post, H. Zan and P. Casali.   2022.  Rad52 mediates class-switch DNA recombination to IgD through microhomology-mediated alternative end-joining.  Nature Commun. 13: 980. PMID: 35190531  PMCID: PMC8861003 DOI: 10.1038/s41467-022-28576-2.
  • Casali, P., S. Li, G. Morales, C.C. Daw, D.P. Chupp, A.D. Fisher and H. Zan.  2021. Epigenetic modulation of class-switch DNA recombination to IgA through selective downregulation of Smad2, Smad3 and Smad4. Front. Immunol. 12:761450. DOI: 10.3389/fimmu.2021.761450  PMID: 34868004  PMCID: PMC8635144.
  • Moroney, J.B., D.P. Chupp, Z. Xu, H. Zan and P. Casali. 2020. Epigenetics of the antibody and autoantibody response.  Curr. Op. Immunol. 67:75-86.  DOI: 10.1016/j.coi.2020.09.004
  • Moroney, A. Vasudev, A. Pertsemlidis, H. Zan and P. Casali.  2020.  Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells.  Nature Commun. 11:543.  DOI:10.1038/s41467-020-19242-6 PMID: 33116135 PMCID: PMC7595102.
  • Casali, P., T. Shen T., Y. Xu, Z. Qiu, D.P. Chupp, J. Im, Z. Xu and H. Zan. 2020. Estrogen reverses HDAC Inhibitor-mediated repression of Aicda and class-switching in antibody and autoantibody responses by downregulation of miR-26a.  Front. Immunol.11:491. DOI: 10.3389/fimmu.2020.00491.
  • Gan H., T. Shen, D.P. Chupp, J.R. Taylor, H.N. Sanchez, X. Li, Z. Xu, H. Zan and P. Casali. 2020.  B cell Sirt1 deacetylates histone and non-histone proteins to modulate AID expression and the antibody response. Science Adv. 6: eaay2793. PMCID: PMC7112761.
  • Yan, H.,  M. Fernandez, J. Wang, S. Wu, R. Wang, Z. Lou, J.B. Moroney, C.E. Rivera, J.R. Taylor, H. Gan, H. Zan, D. Kolvaskyy, D. Liu, P. Casali* and Z. Xu*.  2020.  B cell endosomal RAB7 promotes TRAF6 K63 polyubiquitination and NF-kB activation for antibody class-switching.  J. Immunol. 204: 1-15. [*equal contributors].  DOI: 10.4049/jimmunol.2000342.
  • Sanchez, H.N.*, J.B. Moroney*, H. Gan, T. Shen, J. Im, T. Li, J.R. Taylor, H. Zan and P. Casali.  2020.  B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids.  Nature Commun. 11:60 [*equal contributors]. PMCID: PMC6940392.
  • Zan, H., C. Tat, Z. Qiu, J.A. Guerrero, J. R. Taylor, T. Shen and P. Casali.  2017.  Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.  Nature Commun. 8:14244. PMID: 28176781; PMCID: PMC5309807. DOI: 10.1038/ncomms14244.
  • Catalan-Dibene, J, M.I. Vazquez, V.P. S.P. Luu, Nuccio, A. Karimzadeh, J.M. Kastenschmidt, S.A. Villalta, I. Ushach, E.J. Pone, P. Casali, M. Raffatellu, M. Burkhardt, M. Hernandez-Ruiz, G. Heller, P.A. Hevezi and A. Zlotnik.  2017.  Identification of IL-40, a Novel B Cell-Associated Cytokine. J. Immunol. 199:3326-3335; DOI:10.4049/jimmunol.1700534; PMID: 28978694.
  • Sanchez, H.N.*, T. Shen*, D. Garcia, Z. Lai, P. Casali and H. Zan.  2017. Genome-wide analysis of HDAC inhibitor-mediated modulation of microRNAs and mRNAs in B cells induced to undergo class switch DNA recombination and plasma cell differentiation.  [*equal contributors and corresponding authors].  J. Vis. Exp., 127; PMID: 28994753; DOI:10.3791/55135.
  • Casali, P.  2017. DNA recombination and somatic hypermutation in the immune system. In: Lewin’s GENES XII, J.E. Krebs, E.S. Goldstein, S.T. Kilpatrick, Eds. (12th Edition), Jones & Bartlett Publishers.  Boston, Toronto, London, Singapore.  Chapter 16, pages 397-439.
  • Lam, T., D.V. Kulp, R. Wang, Z. Lou, J., Taylor, Q. Zhong, Z. Wang, H. Zan, D. Ivanov, G. Zhong, P. Casali* and Z. Xu*.  2016.  Small molecule inhibitor of Rab7 impairs B cell class-class switching and plasma cell survival to dampen the autoantibody response in murine lupus [*equal contributors and corresponding authors].   J. Immunol. 197:3792-3805. PMID: 27742832; PMCID: PMC5113143; DOI: 10.4049/jimmunol.1601427
  • Zan, H. and P. Casali.  2016.   Epigenetics of B cells and antibody responses.  Front.  Immunol. 6:656. PMID: 26793194; PMCID: PMC4707482; DOI: 10.3389/fimmu.2015.00656
  • Sanchez, H.N., H. Gan, J.B. Moroney, C.C. Daw, D.P. Chupp, J.R. Taylor, H. Zan and P. Casali. 2018.   B cell-intrinsic epigenetic modulation of local and systemic antibody responses by gut microbiota through catabolic short-chain fatty acids. Submitted to Nature Immunol.
  • Wang, R., H. Yan, M. Fernandez, P. Casali and Z. Xu. 2018. Inhibition of Rab7 by a small molecule compound arrests growth of diffused large B cell lymphoma in vitro and in vivo. Submitted to J. Immunol.
  • Yan, H., R. Wang, M. Fernandez, C. E. Rivera, H. N. Sanchez, X.-D. Li, N. Zhang, X.-Z. Meng, C. A. Hunter, Y. Xiang, H. Zan, P. Casali and Z. Xu.  2017.  B lymphocytes are a major source of paracrinic IL-27 that signals through re-distributed receptors and collaborates with IFN-gamma to critically drive class-switched antibody responses and anti-viral immunity.  Submitted to Cell Rep.
  • Catalan-Dibene, J, M.I. Vazquez, V.P. S.P. Luu, Nuccio, A. Karimzadeh, J.M. Kastenschmidt, S.A. Villalta, I. Ushach, E.J. Pone, P. Casali, M. Raffatellu, M. Burkhardt, M. Hernandez-Ruiz, G. Heller, P.A. Hevezi and A. Zlotnik.  2017.  Identification of IL-40, a Novel B Cell-Associated Cytokine. J. Immunol. 199:3326-3335; DOI:10.4049/jimmunol.1700534; PMID: 28978694.
  • Sanchez, H.N.*, T. Shen*, D. Garcia, Z. Lai, P. Casali and H. Zan.  2017. Genome-wide analysis of HDAC inhibitor-mediated modulation of microRNAs and mRNAs in B cells induced to undergo class switch DNA recombination and plasma cell differentiation.  [*equal contributors and corresponding authors].  J. Vis. Exp., 127; PMID: 28994753; DOI:10.3791/55135.
  • Zan, H., C. Tat, Z. Qiu, J.A. Guerrero, J. R. Taylor, T. Shen and P. Casali.  2017.  Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.  Nature Commun. 8:14244. PMID: 28176781; PMCID: PMC5309807. DOI: 10.1038/ncomms14244.
  • Casali, P.  2017. DNA recombination and somatic hypermutation in the immune system. In: Lewin’s GENES XII, J.E. Krebs, E.S. Goldstein, S.T. Kilpatrick, Eds. (12th Edition), Jones & Bartlett Publishers.  Boston, Toronto, London, Singapore.  Chapter 16, pages 397-439.
  • Lam, T., D.V. Kulp, R. Wang, Z. Lou, J., Taylor, Q. Zhong, Z. Wang, H. Zan, D. Ivanov, G. Zhong, P. Casali* and Z. Xu*.  2016.  Small molecule inhibitor of Rab7 impairs B cell class-class switching and plasma cell survival to dampen the autoantibody response in murine lupus [*equal contributors and corresponding authors].   J. Immunol. 197:3792-3805. PMID: 27742832; PMCID: PMC5113143; DOI: 10.4049/jimmunol.1601427
  • Zan, H. and P. Casali.  2016.   Epigenetic of B cells and antibody responses.  Front.  Immunol. 6:656. PMID: 26793194; PMCID: PMC4707482; DOI: 10.3389/fimmu.2015.00656
  • Zan, H. and P. Casali.  2015.  Epigenetics of peripheral B cells differentiation and the antibody response.  Front. Immunol.  6:631. PMID: 26697022; PMCID: PMC4677338.  http://dx.doi.org/10.3389/fimmu.2015.00631
  • Lou, Z., P. Casali and Z. Xu.  2105.  Role of intracellular membrane-associated proteins in antibody responses: modulation by microRNAs in B cells.  Front. Immunol. 6:537. PMID: 26579118; PMCID: PMC4620719.  http://dx.doi.org/10.3389/fimmu.2015.00537
  • Shen, T., H.N. Sanchez, H. Zan and P. Casali.  2015.  Genome-wide analysis reveals selective modulation of microRNAs and mRNAs by histone deacetylase inhibitor in B cells induced to undergo class-switch DNA recombination and plasma cell differentiation.  Front. Immunol. 6:627.  PMID: 26697020; PMCID: PMC4677488.     http://dx.doi.org/10.3389/fimmu.2015.00627.
  • Pone E. J., T. Lam, Z. Lou, R. Wang, Y. Chen, D.-F. Liu, A. L. Edinger, Z. Xu and P. Casali. 2015. B cell Rab7 mediates induction of activation-induced cytidine deaminase expression and class-switching in T-dependent and T-independent antibody responses.  J. Immunol. 194: 3065-3078.  PMID: 25740947; PMCID: PMC4643723.
  • Pone E. J., Z. Lou, T. Lam, M. L. Greenberg, R. Wang, Z. Xu and P. Casali. 2015. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.  Autoimmunity 48: 1-12.  PMID: 25536171; PMCID: PMC4625915.
  • White, C.A., E.J. Pone, T. Lam, C. Tat, K.L. Hayama, G. Li, H. Zan & P. Casali.  2014.  Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses.  J. Immunol. 193:5933-5950. PMID: 25392531; PMCID: PMC4258531.
  • Morgado, P., D.M. Sudarshana , L. Gov, K.S. Harker, T. Lam, P. Casali, J.P. Boyle and M.B. Lodoen.  2014.  Type II Toxoplasma gondii induction of CD40 on infected macrophages enhances interleukin-12 responses.  Infect. Immun.  82:4047-4055. PMID: 25024369; PMCID: PMC4187859.
  • Zan, H., C. Tat and P. Casali.  2014.  MicroRNAs in lupus.  Autoimmunity 47:272-275. PMID: 24826805; PMCID: PMC4239026.
  • Casali, P.  2014. DNA recombination and somatic hypermutation in the immune system.  In: Lewin’s GENES XI, J.E. Krebs, E.S. Goldstein, S.T. Kilpatrick, Eds. (11th Edition), Jones & Bartlett Publishers.  Boston, Toronto, London, Singapore.  Chapter 18, pages 459-507. [Web Link]
  • Zan, H. and P. Casali.  2014.  Immunoglobulin somatic hypermutation and class switch DNA recombination.  In: Encyclopedia of Medical Immunology.    Vol. 1. Autoimmune Diseases, I.R. Mackay & N.L. Rose, Eds.  Springer-Verlag GmbH, Heidelberg, 2014. Pages 517-528. [Web Link]
  • Lam, T.S., L.M. Thomas, C.A. White, G. Li, E.J. Pone, Z. Xu and P. Casali.  2013.  Scaffold functions of 14-3-3 adaptors in B cell immunoglobuin class switch DNA recombination.  PLOS ONE 8: e80414, 1-15. PMID: 24282540; PMCID: PMC3840166.
  • Li, G., E.J. Pone, T. Mai, T.S. Lam, C.A. White, K.L. Hayama, H. Zan, Z. Xu and P. Casali.  2013.  Combinatorial H3K9acS10ph histone modifications in IgH locus S regions target 14-3-3 adaptors and AID to specify antibody class switch DNA recombination.  Cell Rep. 5:702-714.  PMID: 24209747; PMCID: PMC3951903.
  • Li, G., H. Zan, Z. Xu and P. Casali.  2013.  Epigenetics of the antibody response.  Trends Immunol. 34:460-470.  PMID: 23643790; PMCID: PMC3744588.
  • Mai, T., E.J. Pone, G. Li, J. Moehlman, Z. Xu and P. Casali.  2013.  Induction of activation-induced cytidine deaminase-targeting adaptor 14-3-3g is mediated by NF-kB-dependent recruitment of CFP1 to the 5’-CpG-3’-rich 14-3-3g promoter and sustained by E2A.  J. Immunol.  191:1895-1906. PMID: 23851690; PMCID: PMC3833273.
  • Park, S.-R., P.H. Kim, K.S. Lee, S.H. Lee, G.Y. Seo, Y.C. Yoo, J. Lee and P. Casali.  2013.  APRIL stimulates NF-kB-mediated HoxC4 induction for AID expression in mouse B cells.  Cytokine 61:608-613. PMID: 23178148; PMCID: PMC3723325.