Nicholas Chiorazzi, physician and researcher, is Head of the Karches Center for Chronic Lymphocytic Leukemia Research at The Feinstein Institute for Medical Research in Manhasset, NY.
Dr. Nicholas Chiorazzi received his M.D. from Georgetown University School of Medicine and completed 4 years of internal medicine training in the Cornell Cooperating Hospitals program at North Shore University Hospital and Memorial Sloan-Kettering Cancer Center. He is also trained in Rheumatology and in Allergy-Clinical Immunology.
Dr. Chiorazzi was a research fellow in immunology at Harvard University in the department of Baruj Benacerraf, M.D., who a few years later shared the Nobel Prize in Physiology or Medicine. Dr. Chiorazzi was then worked with Henry G. Kunkel at The Rockefeller University. At Rockefeller, his time was spent studying human B cells in normal and disease settings. In 1987, Dr. Chiorazzi was appointed Chief of the then newly created Division of Rheumatology & Allergy-Clinical Immunology at North Shore University Hospital. In 2000, he was appointed the first Director and CEO of the Feinstein Institute for Medical Research, a position he held until January 2006. Dr. Chiorazzi is currently Professor of Medicine and of Cell Biology in the Albert Einstein College of Medicine and Head of the Karches Center for Chronic Lymphocytic Leukemia Research at The Feinstein Institute for Medical Research.
Dr. Chiorazzi's research interests revolve around understanding the activation and maturation of B-lymphocytes in health and disease, in particular chronic lymphocytic leukemia (CLL). Dr. Chiorazzi and his colleagues have demonstrated that: CLL cells are responsive to signals from the internal microenvironment, in particular those delivered by the B-cell antigen receptor (BCR) leading to leukemic cell proliferation and maturation or death; BCR-induced signals are likely delivered by common self antigens and are mediated through sets of BCRs of remarkably similar amino acid structure; patients with CLL segregate into two subgroups based on BCR structure that differ dramatically in clinical outcome; CLL cells proliferate and die in vivo at rates higher than originally appreciated. These findings have led to the view that (auto)antigen drive is a promoting factor in the development and evolution of CLL and have been a pivotal in refining patient prognosis.
Awards and honors
Election to the American Society for Clinical Investigation, 1986
Member of the Association of American Physicians
Scientific Leadership Award from The S.L.E. Foundation, Inc., 2000
Binet-Rai Medal for Outstanding Contribution to CLL Research
Past President of the Association for Patient-Oriented Research
Contributing Editor: Molecular Medicine (journal)
Bagnara D, Kaufman M, Calissano C, Marsilio S, Patten P, Chum P, Yan X-J, Allen SL, Lee A, Gregersen PK, Rai KR, Chiorazzi N. (2011) A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease" Blood 117: 5463-5472
Chiorazzi N, Ferrarini M. (2011) Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities" Blood 117: 1781-1791
Chu CC, Catera R, Zhang L, Didier S, Agagnina BM, Damle RN, Kaufman MS, Kolitz JE, Allen SL, Rai KR, Chiorazzi N. (2010) Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed non-muscle myosin heavy chain IIA: Implications for patient outcome and cell of origin" Blood 115: 3907-3915
Calissano C, Damle RN, Hayes G, Murphy EJ, Hellerstein MK, Sison C, Kaufman MS, Kolitz JE, Allen SL, Rai KR, Chiorazzi N. (2009) In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia" Blood 2009; 114: 4832-4942
Seiler T, Woelfle M, Yancopoulos Y, Catera R, Li W, Hatzi K, Moreno C, Torres M, Paul S, Dohner H, Stilgenbauer S, Kaufman MS, Kolitz JE, Allen SL, Rai KR, Chu CC, Chiorazzi N. (2009) Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells" Blood 114: 3615-3624
Grubor VD, Krasnitz A, Troge JE, Meth JL, Lakshmi B, Kendall JT, Yamrom B, Alex G, Pai D, Navin N, Hufnagel LA, Lee Y-H, Cook K, Allen SL, Rai KR, Damle RN, Calissano C, Chiorazzi N, Wigler MH, Esposito D. (2009) Novel genomic alterations and clonal evolution in Chronic Lymphocytic Leukemia revealed by Representational Oligonucleotide Microarray Analysis (ROMA)" Blood 113: 1294-303
Chu CC, Catera R, Hatzi K, Yan X-J, Zhang l, Wang XB, Fales HM, Allen SL, Kolitz JE, Rai KR, Chiorazzi N. (2008) Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize non-muscle myosin heavy chain IIA" Blood 112:5122-5129.
Catera R, Silverman GJ, Hatzi K, Seiler TM, Didier S, Zhang L, Herve M, Meffre E, Oscier DG, Vlassara H, Chen Y, Allen SL, Rai KR, Chu CC, Chiorazzi N. (2008) Chronic lymphocytic leukemia cells recognize conserved epitopes associated with apoptosis and chemical modifications. Mol Med. 14: 665-674.
Li F-J, Ding S, Pan J, Shakhmatov MA, Kashentseva E, Wu J, Li Y, Soong S-J, Chiorazzi N, Davis RS. (2008) FCRL2 expression predicts IgVH mutation status and clinical progression in chronic lymphocytic leukemia" Blood 112:179-187.
Damle RN, Temburni S, Calissano C, Yancopoulos S, Banapour T, Sison C, Allen SL, Rai KR, Chiorazzi N. (2007) CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells" Blood 110: 3352-3359.
Chiorazzi N, Ferrarini M. (2006) Evolving view of the in-vivo kinetics of chronic lymphocytic leukemia B cells. Hematology (Am Soc Hematol Educ Program). 273-278.
Ghiotto F, Fais F, Albesiano E, Sison C, Valetto A, Gaidano G, Reinhardt J, Kolitz JE, Rai KR, Allen SL, Ferrarini M, Chiorazzi N. (2006) Similarities and differences between the light and heavy chain Ig variable region gene repertoires in chronic lymphocytic leukemia. Mol Med. 12: 300-308.
Yan X-J, Albesiano E, Zanesi N, Yancopoulos S, Sawyer A, Romano E, Petlickovski A, Efremov DG, Croce CM, Chiorazzi N. (2006) B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia" Proc Natl Acad Sci USA 103:11713-11718.
Herve M, Xu K, Ng Y-S, Wardemann H, Albesiano E, Messmer BT, Chiorazzi N, Meffre E. (2005) Unmutated and mutated chronic lymphocytic leukemia derive from self-reactive B cell precursors despite expressing different antibody reactivity" J Clin Invest 115: 1636-1643.
Messmer BT, Messmer D, Allen SL, Kolitz JE, Kudalkar P, Cesar D, Murphy EJ, Koduru P, Ferrarini M, Zupo S, Cutrona G, Damle RN, Wasil T, Rai KR, Hellerstein MK, Chiorazzi N. (2005) In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells" J Clin Invest 115: 755-764.
Chiorazzi N, Rai KR, Ferrarini M. (2005) Mechanisms of Disease. Chronic Lymphocytic Leukemia" N Engl J Med 352: 804-815.
Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Damle R, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N. (2004) Distinct sets of stereotyped antigen receptors indicate the limited primary structural diversity in antigen-binding sites of CLL B cells" J Exp Med 200: 519-525.
Messmer BT, Albesiano E, Messmer D, Chiorazzi N. (2003) The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process" Blood 103: 3490-3495.
Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, Ikematsu H, Allen SL, Kolitz J, Rai KR, Nardini M, Tramontano A, Ferrarini M, Chiorazzi N. (2004) Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia" J Clin Invest 113: 1008-1016.
Damle RN, Batliwalla FM, Ghiotto F, Valetto A, Albesiano E, Sison C, Allen SL, Kolitz J, Vinciguerra VP, Kudalkar P, Wasil T, Rai KR, Ferrarini M, Gregersen PK, Chiorazzi N. (2004) Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by Ig V gene mutations" Blood 103: 375-382.
Chiorazzi N, Messmer BT, Damle RN, Alllen SL, Rai KR, Ferrarini M. (2003) Unraveling the biology of chronic lymphocytic leukemia. Hematology (Am Soc Hematol Educ Program). 153-159.
Albesiano E, Messmer BT, Damle RN, Allen SL, Rai KR, Chiorazzi N. (2003) Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone" Blood 102: 3333-3339.
Chiorazzi N, Ferrarini M. (2003) B Cell Chronic Lymphocytic Leukemia: Lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol. 21: 841-894.
Damle RN, Ghiotto F, Valetto A, Albesiano E, Fais F, Yan X-J, Sison CP, Allen SL, Kolitz J, Schulman P, Vinciguerra VP, Budde P, Frey J, Rai KR, Ferrarini M, Chiorazzi N. (2002) B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes" Blood 99: 4087-4093.
Gurrieri C, McGuire P, Zan H, Yan X-J, Cerutti A, Albesiano E, Allen SL, Vinciguerra V, Rai KR, Ferrarini M, Casali P, Chiorazzi N. (2002) Chronic lymphocytic leukemia B cells can undergo somatic hypermutation and intraclonal Ig VHDJH gene diversification" J Exp Med 196:629-639.
Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia" Blood 94: 1840-1847.
Fais F, Ghiotto F, Hashimoto S, Sellars B, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder HW, Jr., Ferrarini M, Chiorazzi N. (1998) Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors" J Clin Invest 102: 1515-1525.
Fais F, Sellars B, Ghiotto F, Yan X-J, Dono M, Allen SL, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Schuster M, Vinciguerra VP, Rai K, Stevenson F, Gregersen PK, Ferrarini M, Chiorazzi N. (1996) Molecular examples of in vivo isotype class switching in IgM+ chronic lymphocytic leukemia B cells" J Clin Invest 98: 1659-1666.
Hashimoto S, Wakai M, Allen SL, Lichtman SM, Schulman P, Vinciguerra VP, Ferrarini M, Silver J, Chiorazzi N. (1995) Somatic diversification and selection of immunoglobulin heavy and light chain variable region genes in IgG+, CD5+ chronic lymphocytic leukemia B cells" J Exp Med 181: 1507-1517.
Sthoeger ZM, Wakai M, Tse DB, Vinciguerra VP, Allen SL, Budman DR, Lichtman SM, Schulman P, Weiselberg LR, Chiorazzi N. (1989) Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia" J Exp Med 169: 255-268.
