
Associate Professor, Department of Investigative Medicine
Biosketch
Dr. Holodick performed her undergraduate work at Northeastern University in Boston, Massachusetts. She obtained her PhD in Immunology from Boston University in 2009, working on signaling and development of B-1 cells. Dr. Holodick expanded her work on B-1 cells during a postdoctoral fellowship at the Feinstein Institute for Medical Research in Manhasset, New York. During this time, she focused her research on the role of B-1 cells in infection during aging. Recently, Dr. Holodick was appointed to Assistant Professor in the Center for Immunobiology and Department of Biomedical Sciences at Western Michigan University School of Medicine. She currently studies the role of B-1 cells in protection from pneumococcal infection in sickle cell disease and B-1 cell development in young and aged mice.
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Education and Training
- PhD 2009, Immunology, Boston University
- BS 2003, Biology, Northeastern University
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Publications
Gutknecht M.F., Holodick N.E., Rothstein T.L. B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells iScience. 2023;26
Webster S.E., Tsuji N.L., Clemente M.J., Holodick N.E. Age-related changes in antigen-specific natural antibodies are influenced by sex Frontiers in Immunology. 2023;13
Srikakulapu P., Pattarabanjird T., Upadhye A., Bontha S.V., Osinski V., Marshall M.A., Garmey J., Deroissart J., Prohaska T.A., Witztum J.L., Binder C.J., Holodick N.E., Rothstein T.L., McNamara C.A. B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis Frontiers in Immunology. 2022;13
Webster S.E., Ryali B., Clemente M.J., Tsuji N.L., Holodick N.E. Sex Influences Age-Related Changes in Natural Antibodies and CD5<sup>+</sup> B-1 Cells Journal of Immunology. 2022;208:1755-1771.
Tsuji N., Rothstein T.L., Holodick N.E. Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age Journal of immunology (Baltimore, Md. : 1950). 2020;205:741-759.
Ghosn E., Dorshkind K., Herzenberg L.A., Holodick N., Kantor A., Montecino-Rodriguez E., Rothstein T.L., Silverman G., Yang Y., Yoder M.C., Yoshimoto M. B1 B cell progenitors Science. 2019;364:248.
Upadhye A., Srikakulapu P., Gonen A., Hendrikx S., Perry H.M., Nguyen A., McSkimming C., Marshall M.A., Garmey J.C., Taylor A.M., Bender T.P., Tsimikas S., Holodick N.E., Rothstein T.L., Witztum J.L., McNamara C.A. Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked to Human Coronary Atherosclerosis Circulation research. 2019;125:e55-e70.
Aziz M., Ode Y., Zhou M., Ochani M., Holodick N.E., Rothstein T.L., Wang P. B-1a cells protect mice from sepsis-induced acute lung injury Molecular Medicine. 2018;24
Aziz M., Holodick N., Rothstein T., Wang P. B-1a cells protect mice from sepsis: Critical role of creb Journal of Immunology. 2017;199(2):750-760.
Hernandez A., Holodick N. Editorial: Natural antibodies in health and disease Frontiers in Immunology. 2017;8(DEC)
Holodick N., Rodríguez-Zhurbenko N., Hernández A. Defining natural antibodies Frontiers in Immunology. 2017;8(JUL)
Kaku H., Holodick N., Tumang J., Rothstein T. CD25<sup>+</sup> B-1a cells express Aicda Frontiers in Immunology. 2017;8
Martínez D., Pupo A., Cabrera L., Raymond J., Holodick N.E., Hernández A.M. B-CD8<sup>+</sup> T cell interactions in the anti-idiotypic response against a self-antibody Journal of Immunology Research. 2017;2017
Holodick N., Vizconde T., Hopkins T., Rothstein T. Age-related decline in natural igm function: Diversification and selection of the B-1a cell pool with age Journal of Immunology. 2016;196(10):4348-4357.
Holodick N.E., Zeumer L., Rothstein T.L., Morel L. Expansion of B-1a cells with germline heavy chain sequence in lupus mice Frontiers in Immunology. 2016;7(MAR)
Kramer J.M., Holodick N.E., Vizconde T.C., Raman I., Yan M., Li Q.Z., Gaile D.P., Rothstein T.L. Analysis of IgM antibody production and repertoire in a mouse model of Sjögren’s syndrome Journal of Leukocyte Biology. 2016;99(2):321-331.
Olofsson P.S., Steinberg B., Sobbi R., Cox M.A., Ahmed M.N., Oswald M., Szekeres F., Hanes W.M., Introini A., Liu S.F., Holodick N.E., Rothstein T.L., Lövdahl C., Chavan S.S., Yang H., Pavlov V.A., Broliden K., Andersson U., Diamond B., Miller E.J., Arner A., Gregersen P.K., Backx P.H., Mak T.W., Tracey K.J. Blood pressure regulation by CD4<sup>+</sup> lymphocytes expressing choline acetyltransferase Nature Biotechnology. 2016;34(10):1066-1071.
Quách T.D., Hopkins T.J., Holodick N.E., Vuyyuru R., Manser T., Bayer R.L., Rothstein T.L. Human B-1 and B-2 B cells develop from Lin<sup>-</sup>CD34<sup>+</sup>CD38<sup>lo</sup> stem cells Journal of Immunology. 2016;197(10):3950-3958.
Rothstein T., Holodick N. Activation of B-1 Cells Encyclopedia of Immunobiology. 2016;3:237-243.
Aziz M., Holodick N.E., Rothstein T.L., Wang P. The role of B-1 cells in inflammation Immunologic Research. 2015;63(1-3):153-166.
Holodick N., Rothstein T. B cells in the aging immune system: Time to consider B-1 cells Annals of the New York Academy of Sciences. 2015;1362(1):176-187.
Rothstein T., Herzenberg L., Holodick N., Ghosn E. B-1 Cell Development and Function Annals of the New York Academy of Sciences. 2015;1362(1):v-vi.
Holodick N., Vizconde T., Rothstein T. B-1a Cell diversity: Nontemplated addition in B-1a cell ig is determined by progenitor population and developmental location Journal of Immunology. 2014;192(5):2432-2441.
Holodick N., Vizconde T., Rothstein T. Splenic B-1a cells expressing CD138 spontaneously secrete large amounts of immunoglobulin in naïve mice Frontiers in Immunology. 2014;5(MAR)
Chen S., Batliwalla F., Holodick N., Yan X., Yancopoulos S., Croce C., Rothstein T., Chiorazzi N. Autoantigen can promote progression to a more aggressive TCL1 leukemia by selecting variants with enhanced B-cell receptor signaling Proceedings of the National Academy of Sciences of the United States of America. 2013;110(16)
Holodick N., Rothstein T. Atypical response of B-1 cells to BCR ligation: A speculative model Frontiers in Immunology. 2013;4(DEC)
Rothstein T., Griffin D., Holodick N., Quach T., Kaku H. Human B-1 cells take the stage Annals of the New York Academy of Sciences. 2013;1285:97-114.
Griffin D., Quach T., Batliwalla F., Andreopoulos D., Holodick N., Rothstein T. Human CD11b<sup>+</sup> B1 cells are not monocytes: A reply to "Gene profiling of CD11b<sup>+</sup> and CD11b<sup>-</sup> B1 cell subsets reveals potential cell sorting artifacts" Journal of Experimental Medicine. 2012;209(3):434-436.
Griffin D., Holodick N., Rothstein T. Correction: Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20<sup>+</sup>CD27<sup>+</sup>CD43<sup>+</sup>CD70<sup>-</sup> Journal of Experimental Medicine. 2011;208(4):871.
Griffin D., Holodick N., Rothstein T. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20<sup>+</sup>CD27<sup>+</sup>CD43<sup>+</sup>CD70<sup>-</sup> Journal of Experimental Medicine. 2011;208(1):67-80.
Griffin D., Holodick N., Rothstein T. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20<sup>+</sup>CD27<sup>+</sup>CD43<sup>+</sup>CD70<sup>-</sup> (The Journal of Experimental Medicine (2011), 208, 1, (67-80)) Journal of Experimental Medicine. 2011;208(2):409.
Griffin D.O., Holodick N.E., Rothstein T.L. Human B1 cells are CD3<sup>-</sup>: A reply to "A human equivalent of mouse B-1 cells?" and "The nature of circulating CD27<sup>+</sup>CD43<sup>+</sup> B cells" Journal of Experimental Medicine. 2011;208(13):2566-2569.
Tumang J.R., Holodick N.E., Vizconde T.C., Kaku H., Francés R., Rothstein T.L. A CD25<sup>-</sup> positive population of activated B1 cells expresses LIFR and responds to LIF Frontiers in Immunology. 2011;2
Holodick N., Tumang J., Rothstein T. Immunoglobulin secretion by B1 cells: Differential intensity and IRF4-dependence of spontaneous IgM secretion by peritoneal and splenic B1 cells European Journal of Immunology. 2010;40(11):3007-3016.
Holodick N., Tumang J., Rothstein T. Continual signaling is responsible for constitutive ERK phosphorylation in B-1a cells Molecular Immunology. 2009;46(15):3029-3036.
Holodick N.E., Repetny K., Zhong X., Rothstein T.L. Adult BM generates CD5<sup>+</sup> B1 cells containing abundant N-region additions European Journal of Immunology. 2009;39(9):2383-2394.
Repetny K.J., Zhong X., Holodick N.E., Rothstein T.L., Hansen U. Binding of LBP-1a to specific immunoglobulin switch regions in vivo correlates with specific repression of class switch recombination European Journal of Immunology. 2009;39(5):1387-1394.
Zhong X., Lau S., Bai C., Degauque N., Holodick N., Steven S., Tumang J., Gao W., Rothstein T. A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and lupus-prone mice Arthritis and Rheumatism. 2009;60(12):3734-3743.
Husain Z., Holodick N., Day C., Szymanski I., Alper C. Increased apoptosis of CD20<sup>+</sup> IgA<sup>+</sup> B cells is the basis for IgA deficiency: The molecular mechanism for correction in vitro by IL-10 and CD40L Journal of Clinical Immunology. 2006;26(2):113-125.
Barrington R.A., Zhang M., Zhong X., Jonsson H., Holodick N., Cherukuri A., Pierce S.K., Rothstein T.L., Carroll M.C. CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses Journal of Immunology. 2005;175(5):2859-2867.
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Presentations
- Age-Related Changes in Antigen-Specific Natural Antibodies Are Influenced by Sex. Webster SE, Tsuji N, Clemente MJ, Holodick NE, Gordon Research Conference: Sex Differences in Immunity, Ventura, California, 04/2923
- Loss of estrogen signaling alters B-1 cells in a model of polycystic ovarian syndrome. Vergara R, Webster S, Hurley I, Holodick N, 42nd Annual Kalamazoo Community and Health Sciences Research Day, Kalamazoo, Michigan, 04/2024
- Analysis of the B-1 cell repertoire post-Pneumovax23 vaccination in a mouse model of sickle cell disease. Les SM, Tsuji NL, Holodick NE, 42nd Annual Kalamazoo Community and Health Sciences Research Day, Kalamazoo, Michigan, 04/2024
- Impact of TLR stimulation on the CD5+ and CD5- B-1 cell repertoires with age. Helmich M, Webster S, Tsuji N, Holodick N, 42nd Annual Kalamazoo Community and Health Sciences Research Day, Kalamazoo, Michigan, 04/2024
- B Cell-Derived Natural IgM Maintains Retinal Homeostasis throughout Lifespan. Les SM, Webster SE, Heck DM, Jones P, Clemente MJ, Holodick NE, 41st Annual Kalamazoo Community Medical & Health Sciences Research Day, Kalamazoo, Michigan, 05/2023
- Age-Related Changes in Antigen-Specific Natural Antibodies Are Influenced by Sex. Holodick N, Department of Microbiology Seminar at Miami University, Oxford, Ohio, 04/2023
- Age-Related Changes in Antigen-Specific Natural Antibodies Are Influenced by Sex. Holodick N, Gordon Research Conference: Sex Differences in Immunity, Ventura, California, 04/2023
- Under Pressure: Genetic and Sex-Based Influences on Natural Antibodies and Natural Antibody Producing Cells. Webster SE, Vergara R, Tsuji N, Heck D, Clemente MJ, Holodick NE, Gordon Research Conference: Sex Differences in Immunity, Ventura, California, 04/2023
- Age-Related Changes in Antigen-Specific Natural Antibodies Are Influenced by Sex. Holodick N, Department of Biological Sciences Seminar at Western Michigan University, Kalamazoo, Michigan, 04/2023
- Influence of age, sex, and environment on the diversity of the murine gut microbiome and expression of pro-inflammatory cytokines. Webster S, Vos D, Rothstein T, Holodick N, 40th Annual Kalamazoo Community Medical and Health Sciences Research Day, Kalamazoo, Michigan, 04/2022
- Immunoglobulin M is Packaged into B Cell-Derived Extracellular Vesicles and Can Be Transferred to Secondary Cells. Gutknecht M, Holodick N, Rothstein T, 40th Annual Kalamazoo Community Medical and Health Sciences Research Day, Kalamazoo, Michigan, 04/2022
- Characterization of Immunoglobulin M in B-Cell-Derived Extracellular Vesicles. Gutknecht M, Holodick N, Rothstein T, 38th Annual Kalamazoo Community Medical and Health Sciences Virtual Research Day, Kalamazoo, Michigan, 04/2021
- Differential Gene Expression in Aged B Cells: A Role for Sex. Ryali B, Holodick N, 38th Annual Kalamazoo Community Medical and Health Sciences Virtual Research Day, Kalamazoo, Michigan, 04/2021
- The Role of IgM in Selection of the Murine B-1A Cell Repertoire with Increasing Age. Ewing P, Tsuji N, Holodick N, 38th Annual Kalamazoo Community Medical and Health Sciences Virtual Research Day, Kalamazoo, Michigan, 04/2021
- Analysis of B cell progenitors in sickle cell disease. Chou J, Holodick N, 36th Annual Kalamazoo Community Medical and Health Sciences Virtual Research Day, Kalamazoo, Michigan, 04/2019