Paolo Casali: Difference between revisions
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{{about|the Italian-American immunologist|the Italian oncologist|Paolo G. Casali}} |
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Paolo Casali | |
|---|---|
| Born | Cremona, Italy |
| Nationality | United States, Italy |
| Education | University of Milan |
| Occupation(s) | Zachry Foundation Distinguished Professor, Chairman |
| Employer | Long School of Medicine University of Texas Health Science Center at San Antonio |
Paolo Casali is an Italian-American immunologist whose research focuses on the molecular mechanisms of B lymphocyte differentiation and antibody gene expression as relevant to autoimmune disorders, cancers, infections and their processes.[1] He is the Zachry Foundation Distinguished Professor and Chairman of the Department of Microbiology, Immunology & Molecular Genetics at the Long School of Medicine, University of Texas Health Science Center at San Antonio.[2]
Education
Casali received a degree in medicine and surgery (M.D.) magna cum laude,[1] from the University of Milan in 1974.[3] He completed an internship at the University of Milan’s School of Medicine & Surgery, as well as obtained National Medical Board Certification.[4] Casali holds two specialty diplomas and board certifications from the University of Milan in the fields of allergy and clinical immunology as well as microbiology and virology.[5] From 1977–1978 he completed his postgraduate work at the World Health Organization's (W.H.O.) Immunology Research and Training Centre where, as W.H.O Medical Officer, he was assigned to ALERT medical facility (then named the All-Africa Leprosy Rehabilitation and Training Center) located in Addis Ababa, Ethiopia.[6]
Research
Casali began his research in the early 1980s as a postdoctoral fellow at the Scripps Research Institute.[4] There he illustrated the modulation of functions of human lymphocytes, including B cells, by pathogenic viruses. Through these experiments, he showed that the measles, influenza, human cytomegalovirus and Epstein-Barr viruses 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 by B lymphocytes, thereby opening a new avenue of research in viral immunobiology.[7]
By 1991 he had coined the term "polyreactive" antibodies.[8] This term derived from his experiments on 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.[4] Following this discovery, he went on to be one of the first investigators, along with Jim Larrick, to adapt the polymerase chain reaction (PCR) to the amplification of expressed antibody 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.[9]
By the early 2000s, Casali's focus continued further on molecular genetics of antibodies, antibody gene class-switch DNA recombination (CSR) and somatic hypermutation (SHM).[10] At the start of his research in the area, 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 have been fundamental in advancing research of the dysregulation of RAB7A, HOXC4 and activation-induced cytidine deaminase (AID) by estrogen in lupus B cells, as derived from patients and lupus mouse models.[11] His most recent work as of 2017 has been devoted to investigating the role of epigenetics—particularly, histone post-translational 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.[4] 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.[citation needed]
Since 2002, Casali has been Editor-in-Chief of Autoimmunity[12] 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, in 2012, 2015 and 2017, respectively.[13]
Because of his pioneering studies of human antibody gene expression and molecular biology of antibody response, Casali was elected "Young Turk" by the American Society for Clinical Investigation in 1992.[4] In 2010, he was elected "Fellow" of the American Association for the Advancement of Science.[4] Casali has been an elected member of the American Association of Immunologists since 1981.[4]
References
- ^ a b "Press release: Immunologist Casali to occupy Zachry Distinguished Chair". UT Health Science Center News. 2013-09-24. Retrieved 2017-10-11.
- ^ "Paolo Casali, M.D." U.T. Health: San Antonio. The University of Texas Health Science Center at San Antonio. Retrieved 21 August 2017.
- ^ "Paolo Casali, M.D." Retrieved 22 August 2017.
- ^ a b c d e f g "Paolo Casali Appointed Department Chair at UT Health Science Center" (PDF). The American Association of Immunologists. October 23, 2017. Retrieved October 23, 2017.
{{cite web}}: Cite has empty unknown parameter:|dead-url=(help) - ^ "Dr Paolo Casali - Harris Search Associates". www.harrisandassociates.com. Retrieved 2017-10-11.
- ^ Gonzalez-Scarano, Francisco (April 2015). "Dr. Paolo Casali researches autoimmune dysfunction". Bexar County Medical Society Magazine.
- ^ Casali, P.; Rice, G. P.; Oldstone, M. B. (1984-05-01). "Viruses disrupt functions of human lymphocytes. Effects of measles virus and influenza virus on lymphocyte-mediated killing and antibody production". Journal of Experimental Medicine. 159 (5): 1322–1337. doi:10.1084/jem.159.5.1322. ISSN 0022-1007. PMC 2187306. PMID 6716049.
- ^ Casali, P.; Notkins, A. L. (November 1989). "CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire". Immunology Today. 10 (11): 364–368. doi:10.1016/0167-5699(89)90268-5. ISSN 0167-5699. PMID 2482031.
- ^ Ikematsu, Hideyuki; Harindranath, Nagaradona; Ueki, Yuji; Notkins, Abner L.; Casali, Paolo (1993-02-15). "Clonal Analysis of a Human Antibody Response". Journal of Immunology. 150 (4): 1325–1337. ISSN 0022-1767. PMC 4667541. PMID 8432980.
- ^ "Paolo Casali". repubblica.it. Retrieved August 15, 2017.
- ^ Epigenetics of B Cells and Antibody Responses, page 4, 2016
- ^ "Taylor and Francis Online". Editor in Chief for Autoimmunity Journal.
- ^ "Google Books". Editor for Chapter 16-Somatic DNA Recombination and Hypermutation in the Immune System.