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Paolo Casali

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Paolo Casali
File:Casali Profile.png
Dr. Casali, Paolo, M.D.
Born
Pizzighettone, Cremona, Italy
NationalityUnited States, Italy
EducationUniversity of Milan
OccupationZachry Foundation Distinguished Professor and Chairman
EmployerUniversity of Texas Health Science Center at San Antonio
Website[1]

Paolo Casali, M.D., is a Zachry Foundation Distinguished Professor and Chairman of the Microbiology, Immunology & Molecular Genetics Department at the University of Texas Health Science Center at San Antonio[1]. He is a world-renowned Italian-American Immunologist whose research focuses on autoimmune disorders and its processes.[2] One of his many notable successes includes his contribution to TNF-α, an FDA approved drug called Adalimumab (brand name Humira).[3]

He is a significant figure in his field, with over 10 papers with over 100 cites.[4]

Education

Dr. Paolo Casali received his degree in medicine and surgery (M.D.), summa cum laude, from University of Milan, Italy, in 1973. By 1974, he completed an internship with the University of Milan’s School of Medicine & Surgery, as well as obtained National Medical Board Certification. Dr. Casali also holds two Specialty Diplomas and Board Certifications from the University of Milan in Allergy and Clinical Immunology as well as Microbiology and Virology. From 1977-1978 he completed his postgraduate work at the World Health Organization (W.H.O.) Immunology Research and Training Centre where, as W.H.O Medical Officer, he was assigned to the All-Africa Leprosy Rehabilitation and Training Center (ALERT) in Addis Ababa, Ethiopia.[1]

Contribution to Science

Dr. Casali began his research in the early 1980s as a postdoctoral fellow at the Scripps Research Institute. There he illustrated the modulation of functions of human lymphocytes, including B cells, by pathogenic viruses. Through these experiments, it is shown that measles virus, influenza virus, human cytomegalovirus and Epstein-Barr virus (EBV) modulated specialized, “luxury” functions of human lymphocytes. Ultimately, his research provided the first clear understanding of how viruses directly modulate human lymphocyte functions, particularly antibody production, thereby opening a new avenue of research in viral immunobiology.[1]

It did not take long for his research to evolve, studying primarily immunochemistry and B cell biology. By 1991 he had coined the term “polyreactive” antibodies. This term derived from his experiments where he revealed the construction of human mAb-producing cell lines, probing the human B cell repertoire, identification of B1 (B1a and B1b) cells and characterization of “polyreactive” antibodies. This research would also formalize the B1a/B1b cell nomenclature. Following this discovery, he went on to be one of the first investigators, along with Dr. Jim Larrick, to adapt the PCR to the amplification of expressed Ig genes in his experiment of human Ig V(D)J gene expression, class-switch DNA recombination (CSR or class switch recombination) and somatic hypermutation (SHM) in human B cells in health and disease.[1][5][6][7][8]

By the early 2000s, his focus changed, and still remains today, on molecular genetics of antibodies, antibody gene class-switch DNA recombination (CSR) and somatic hypermutation (SHM).[9] Starting, his lab mounted a systematic effort to tackle the molecular mechanisms underpinning B cell differentiation in immunity, autoimmunity and lymphomagenesis, by addressing the stimuli and signals inducing CSR/SHM and Aicda expression. The findings in his experiments are fundamental in advancing research of the dysregulation of RAB7A, HOXC4 and AID by estrogen in lupus B cells, as derived from patients and lupus mouse models.[10] However, his most recent work has been devoted to investigating the role of epigenetics, particularly, histone posttranslational modifications and non-coding RNAs, including microRNAs, in targeting and regulating the B cell CSR/SHM machinery and plasma cell differentiation. His investigations have found that HDAC (histone deacetylase) inhibitors (HDIs) specifically downregulate expression of AID and Blimp-1 (master transcription factor of plasma cell differentiation) by upregulating microRNAs that target Aicda or Prdm1 (encoding Blimp-1) 3’-UTR. These specific epigenetic changes effectively modulate CSR/SHM and antibody responses. They also blunt autoantibody responses in lupus-prone mice, thereby alleviating lupus immunopathology, and outline an important role of epigenetic modifications in the regulation of B cell differentiation in autoimmunity.[1][11][12]

In addition to his laboratory findings, he has published, roughly, 200 articles in notable peer-reviewed journals, twenty-five of which have been cited more than 100 times and 5 of which have been cited more than 400 times. Since 2002, he has been Editor-in-Chief of Autoimmunity[13]and has authored the chapter on “DNA recombination and somatic hypermutation in the immune system” in the last three editions (X, XI and XII) of the Lewin’s GENES textbook.[14]

Notable positions include:ref name="UT Health San Antonio"/>

1990 - 1994 Kaplan Cancer Scholar, Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016.

1994 - 2003 Professor of Pathology & Laboratory Medicine (tenured) and Director, Division of Molecular Immunology, Joan and Sanford I. Weill Medical College, Cornell University, New York, NY 10021.

1995 - 2003 Professor of Immunology, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021.

1996 - 2003 Professor, Tri-Institutional MST (M.D. Ph.D.) Program, Cornell University/The Rockefeller University/Memorial Sloan Kettering, New York, NY 10021.

1997 - 2001 Director, Immunology Graduate Program, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University-Memorial Sloan Kettering, New York, NY 10021.

1999 - 2003 Professor of Microbiology and Immunology, Joan and Sanford I. Weill Medical College, Cornell University, New York, NY 10021.

1999 - 2003 Director, N.I.H. Program for Graduate and Postgraduate Training in Immunological Research, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021.

2003 - 2013 Professor of Medicine, School of Medicine, and Professor of Molecular Biology and Biochemistry, School of Biological Sciences, and Member, Cancer Research Institute, University of California, Irvine, CA 92697.

2003 - 2013 Donald L. Bren Chair, School of Medicine, University of California, Irvine, CA 92697. http://today.uci.edu/news/release_detail.asp?key=937

2010 - 2013 Professor of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine

2014 - Zachry Foundation Distinguished Chair in Microbiology and Immunology, School of Medicine, University of Texas Health Science Center.[15][16]

2014 - Professor and Chairman, Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229.[17]

Professional Societies and Organizations

Ordine dei Medici della Provincia di Milano, Italy, 1974 - present.

Gruppo di Cooperazione in Immunologia, Italy, 1979 - present.

Fellow, The American Association for Advancement of Science, 1981 - present.[18]

Young Turk (elected), The American Society for Clinical Investigation, 1992 - present.[19]

Elected Member, The Henry Kunkel Society, 1998 - present.[20]

Selected Publications

(selected publications since 2000)

  • Zan, H., C. Tat, Z. Qiu, J.A. Guerrero, J. R. Taylor, T. Shen and P. Casali. 2016. Rad52 competes with Ku70/Ku86 for binding to switch region DSB ends to modulate immunoglobulin class switch DNA recombination. Nature Commun., submitted.
  • 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. Rab7 inhibitor 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., in press.[21]
  • Casali, P. 2016. 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 1-62. * Casali, P. and H. Zan. 2016. Epigenetic of B cells and antibody responses. Front. Immunol. PMID: 26697022; PMCID: PMC4677338
  • 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 AID expression and class-switching in T-dependent and T-independent antibody responses. J. Immunol. 194: 3065-3078. PMID: 25740947; PMCID: PMC4643723.
  • 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. PMID: 26697020; PMCID: PMC4677488.
  • Zan, H. and P. Casali. 2015. Epigenetics of peripheral B cells differentiation and the antibody response. Front. Immunol. PMID: 26697022; PMCID: PMC4677338.
  • 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.
  • 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
  • Li, G., H. Zan, Z. Xu and P. Casali. 2013. Epigenetics of the antibody response. Trends Immunol. 34:460-470. PMID: 23643790; PMCID: PMC3744588.
  • 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 RepOrts. 5:702-714. PMID: 24209747; PMCID: PMC3951903.
  • Pone, E.J., J. Zhang, T. Mai, C.A. Clayton, G. Li, P. Patel, A. Al-Qahtani, J. Sakakura, H. Zan, Z. Xu and P. Casali. 2012. BCR-signaling synergizes with TLR-signaling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. Nature Commun. 3:767 (1-12). PMID: 22473011; PMCID: PMC3337981.
  • Xu, Z., H. Zan, E.J. Pone, T. Mai and P. Casali. 2012. Immunoglobulin class-switch DNA recombination: induction, targeting and beyond. Nature Rev. Immunol. 12:517-531. PMID: 22728528; PMCID: PMC3545482.
  • Zan, H., C.A. White, L.M. Thomas, T. Mai, G. Li, Z. Xu, J. Zhang and P. Casali. 2012. Rev1 recruits Ung to switch regions and enhances dU glycosylation for immunoglobulin class switch DNA recombination. Cell Reports 2:1220-1232. PMID: 23140944; PMCID: PMC3518390.
  • Casali, P. 2011. DNA recombination and somatic hypermutation in the immune system. In: Lewin’s GENES X, J.E. Krebs, E.S. Goldstein, S.T. Kilpatrick, Eds. (10th Edition), Jones & Bartlett Publishers. Boston, Toronto, London, Singapore. Chapter 18, pages 570-623.
  • Xu, Z., Z. Fulop, G. Wu, S.-R. Park, J. Zhang, E. J. Pone, A. Al-Qahtani, T. Mai, P. Steinacker, L. Thomas, C.A. White, Z. Li, J. R. Yates, III, B. Herron, M. Otto, H. Zan, H. Fu and P. Casali. 2010. 14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′-rich switch regions for class switch DNA recombination. Nature Str. Mol. Biol. 17:1124-1135. PMID: 20729863; PMCID: PMC3645988.
  • Mai, T., H. Zan, J. Zhang, J.S. Hawkins, Z. Xu and P. Casali. 2010. Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class-switch DNA recombination, and somatic hypermutation. J. Biol. Chem. 285: 37797-37810. PMID: 20855884; PMCID: PMC2988384.
  • Zan, H., J. Zhang, S. Ardeshna, M. Greenberg, Z. Xu, S.-R. Park and P. Casali. 2009. Lupus-prone MRLfaslpr/lpr mice display increased AID expression and extensive DNA lesions, comprising deletions and insertions, in the immunoglobulin heavy chain locus: Concurrent upregulation of somatic hypermutation and class switch DNA recombination. Autoimmunity 42:89-103. PMID: 19156553; PMCID: PMC3140875.
  • Park, S.-R., H. Zan, J. Zhang, A. Al-Qahtani, E.J. Pone, Z. Xu, T. Mai and P. Casali. 2009. HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. Nature Immunol. 10:540-550. PMID: 19363484; PMCID: PMC2753990.
  • Elkon, K., & P. Casali. 2008. Nature and functions of autoantibodies. Nature Rev. Rheum. 4:491-498. PMID: 18756274; PMCID: PMC2703183.
  • Xu, Z., S. Pal, H. Zan and P. Casali. 2007. DNA replication to aid somatic hypermutation. Adv. Exp. Med. Biol. 596:111-128. PMID: 17338180; PMCID: PMC3140876.
  • Duquerroy, S., E.A. Stura, S. Bressanelli, S.M. Fabiane, M.C. Vaney, D. Beale, M. Hamon, P. Casali, F.A. Rey, B.J. Sutton and M.J. Taussig. 2007. Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation. J. Mol. Biol. 368:1321-1331. PMID: 17395205; PMCID: PMC4625532.
  • Casali, P., S. Pal, Z. Xu and H. Zan. 2006. DNA repair in antibody somatic hypermutation. Trends Immunol. 27: 313-321. PMID: 16737852; PMCID: PMC4623574.
  • Zan, H., N. Shima, Z. Xu, A. Al-Qahtani, A.J. Evinger, III, Y. Zhong, J.C. Schimenti and P. Casali. 2005. The translation DNA polymerase plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J. 24:3757-3769. PMID: 16222339; PMCID: PMC1276717.
  • Kim, E., C.R. Edmonston, X. Wu, A. Schaffer and P. Casali. 2004. The HoxC4 homeodomain protein mediates activation of the immunoglobulin heavy chain 3′ enhancer hs1,2 in human B cells: relevance to class switch DNA recombination. J. Biol. Chem. 279:42258-42269. PMID: 15252056; PMCID: PMC4631311.
  • Casali, P. and H. Zan. 2004. Class switching and Myc translocation: how does DNA break? Nature Immunol. 5:1101-1103. PMID: 15496946; PMCID: PMC4625794.
  • Zan, H., X. Wu, A. Komori, A. Cerutti, W.K. Holloman and P. Casali. 2003. AID-dependent generation of resected double-strand DNA breaks and recruitment of Rad52/Rad51 in somatic hypermutation. Immunity 18:727-738. PMID: 12818155; PMCID: PMC4625537.
  • Cerutti, A., E. C. Kim, S. Shah, E. J. Schattner, H. Zan, A. Schaffer and P. Casali. 2001. Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells. Nature Immunol. 2:150-156. PMID: 11175813; PMCID: PMC4621971.
  • Zan, H., A. Komori, Z. Li, A. Cerutti, M. Flajinik, M. Diaz and P. Casali. 2001. The translesion DNA polymerase plays a major role in Ig and Bcl-6 somatic hypermutation. Immunity 14:643-653. PMID: 11371365; PMCID: PMC4632985.
  • Li, Z., E.W. Schettino, E. Padlan, H. Ikematsu and P. Casali. 2000. Structure-function analysis of a lupus anti-DNA autoantibody: central role of the heavy chain CDR3 Arg in binding of dsDNA and ssDNA. Eur. J. Immunol. 30:2015-2026. PMID: 10940891; PMCID: PMC4623572.
  • Zan, H., Z. Li, K. Yamaji, P. Dramitinos, A. Cerutti and P. Casali. 2000. B cell receptor engagement and T cell contact induce BCL-6 hypermutation in human B cells: identity with Ig hypermutation. J. Immunol. 165:830-839. PMID: 10878357.
  • Cerutti, A., A. Schaffer, R.G. Goodwin, S. Shah, H. Zan, S. Eli and P. Casali. 2000. Engagement of CD153 (CD30 ligand) by CD30+ T cells inhibits class switch DNA recombination and antibody production in human IgD+ IgM+ B cells. J. Immunol. 165:786-794. PMID: 10878352; PMCID: PMC4621014.

References

  1. ^ a b c d e "Graduate School of Biomedical Sciences". University of Texas Health Science Center at San Antonio. Retrieved 25 July 2017.
  2. ^ "The man with the method". cancerworld.com. Retrieved August 15, 2017.
  3. ^ "Bexar County Medical Society". Bexar County Medical Society Magazine-April-2015. Retrieved 31 March 2015.
  4. ^ "scholar.google.com". Retrieved August 15, 2017.
  5. ^ "February 6, 2015". theparliamentmagazine.com. Retrieved August 15, 2017.
  6. ^ "timeshighereducation.com". Retrieved August 15, 2017.
  7. ^ "Long-term impact of imatinib on metastatic gastrointestinal stromal tumours (GIST)". eortc.org. Retrieved August 15, 2017.
  8. ^ "10-Year Outcomes With Two Dose Levels of Imatinib in Unresectable or Metastatic GIST". ascopost.com. Retrieved August 15, 2017.
  9. ^ "Paolo Casali". repubblica.it. Retrieved August 15, 2017.
  10. ^ Epigenetics of B Cells and Antibody Responses, page 4, 2016
  11. ^ Mechanisms of Lymphocyte Activation and Immune Regulation XI: B Cell Biology, page 110, 2007
  12. ^ Virus-Induced Immunosuppression, page 345, 2012
  13. ^ "Taylor and Francis Online". Editor in Chief for Autoimmunity Journal.
  14. ^ "Google Books". Editor for Chapter 16-Somatic DNA Recombination and Hypermutation in the Immune System.
  15. ^ "AAI News Letter" (PDF). The American Association of Immunologists. Retrieved 1 June 2014.
  16. ^ "UT Health Newsroom". Immunologist Casali to occupy Zachary Distinguished Chair. Retrieved 24 September 2014.
  17. ^ "Profile Page". Professor and Chairman of the Department of Microbiology, Immunology and Molecular Genetics. Retrieved 20 July 2017.
  18. ^ "American Association for the Advancement of Science". Fellow Members - Paolo Casali.
  19. ^ "American Society for Clinical Investigation". Profile Page.
  20. ^ "Henry Kunzel Society Annual Meeting" (PDF). Henry Kunzel Society Members.
  21. ^ "The Journal of Immunology". Contribution to Article.


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