The Department of Investigative Medicine provides ample opportunities for student and residents to participate with faculty in research and scholarly activities. We offer experiences that enable discovery and promote creativity. As a department, we are committed to pursuing inquiry, disseminating knowledge, and fostering critical thinking that encourages lifelong learning.
Research and Scholarly Activity, 2019-20
Recent Publications
Dorshkind K., Höfer T., Montecino-Rodriguez E., Pioli P.D., Rodewald H.R. Do haematopoietic stem cells age? Nature Reviews Immunology. 2020;20:196-202. doi: 10.1038/s41577-019-0236-2.
Kaku H., Ludlow A.V., Gutknecht M.F., Rothstein T.L. FAIM Opposes Aggregation of Mutant SOD1 That Typifies Some Forms of Familial Amyotrophic Lateral Sclerosis Frontiers in Neuroscience. 2020;14 doi: 10.3389/fnins.2020.00110.
Kaku H., Ludlow A.V., Gutknecht M.F., Rothstein T.L. FAIM Opposes Aggregation of Mutant SOD1 That Typifies Some Forms of Familial Amyotrophic Lateral Sclerosis Frontiers in Neuroscience. 2020;14 doi: 10.3389/fnins.2020.00110.
Kaku H., Rothstein T.L. FAIM Is a Non-redundant Defender of Cellular Viability in the Face of Heat and Oxidative Stress and Interferes With Accumulation of Stress-Induced Protein Aggregates Frontiers in Molecular Biosciences. 2020;7 doi: 10.3389/fmolb.2020.00032.
Kaku H., Rothstein T.L. FAIM Is a Non-redundant Defender of Cellular Viability in the Face of Heat and Oxidative Stress and Interferes With Accumulation of Stress-Induced Protein Aggregates Frontiers in Molecular Biosciences. 2020;7 doi: 10.3389/fmolb.2020.00032.
Khan N., Rothstein T.L. The Alternate Pathway for BCR Signaling Induced by IL-4 Requires Lyn Tyrosine Kinase Journal of Molecular Biology. 2020 doi: 10.1016/j.jmb.2020.10.002.
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. doi: 10.4049/jimmunol.1901302.
Ghosn E., Dorshkind K., Herzenberg L., Holodick N., Kantor A., Montecino-Rodriguez E., Rothstein T., Silverman G., Yang Y., Yoder M., Yoshimoto M. B1 B cell progenitors Science. 2019;364:248. doi: 10.1126/science.aax6784.
Guo B., Ludlow A.V., Brightwell A.S., Rothstein T.L. Impairment of PD-L2 positive B1a cells enhances susceptibility to sepsis in RasGRP1-deficient mice Cellular Immunology. 2019;346 doi: 10.1016/j.cellimm.2019.103993.
Montecino-Rodriguez E., Kong Y., Casero D., Rouault A., Dorshkind K., Pioli P.D. Lymphoid-Biased Hematopoietic Stem Cells Are Maintained with Age and Efficiently Generate Lymphoid Progeny Stem Cell Reports. 2019;12:584-596. doi: 10.1016/j.stemcr.2019.01.016.
Pioli P.D. Plasma Cells, the Next Generation: Beyond Antibody Secretion Frontiers in Immunology. 2019;10 doi: 10.3389/fimmu.2019.02768.
Pioli P.D., Casero D., Montecino-Rodriguez E., Morrison S.L., Dorshkind K. Plasma Cells Are Obligate Effectors of Enhanced Myelopoiesis in Aging Bone Marrow Immunity. 2019;51:351-366.e6. doi: 10.1016/j.immuni.2019.06.006.
Rodriguez-Zhurbenko N., Quach T.D., Hopkins T.J., Rothstein T.L., Hernandez A.M. Human B-1 cells and B-1 cell antibodies change with advancing age Frontiers in Immunology. 2019;10 doi: 10.3389/fimmu.2019.00483.
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. doi: 10.1161/CIRCRESAHA.119.315786.
Zhang X., Zhang Y., Ba Z., Kyritsis N., Casellas R., Alt F.W. Fundamental roles of chromatin loop extrusion in antibody class switching Nature. 2019;575:385-389. doi: 10.1038/s41586-019-1723-0.
Zhang Y., Zhang X., Ba Z., Liang Z., Dring E.W., Hu H., Lou J., Kyritsis N., Zurita J., Shamim M.S., Presser Aiden A., Lieberman Aiden E., Alt F.W. The fundamental role of chromatin loop extrusion in physiological V(D)J recombination Nature. 2019;573:600-604. doi: 10.1038/s41586-019-1547-y.
Aziz M., Ode Y., Zhou M., Ochani M., Holodick N., Rothstein T., Wang P. B-1a cells protect mice from sepsis-induced acute lung injury Molecular Medicine. 2018;24 doi: 10.1186/s10020-018-0029-2.
Gallego J., Blanco E., Husain-Krautter S., Madeline Fagen E., Moreno-Merino P., del Ojo-Jiménez J., Ahmed A., Rothstein T., Lencz T., Malhotra A. Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta-analysis Schizophrenia Research. 2018;202:64-71. doi: 10.1016/j.schres.2018.07.019.
Huang W., Quach T.D., Dascalu C., Liu Z., Leung T., Byrne-Steele M., Pan W., Yang Q., Han J., Lesser M., Rothstein T.L., Furie R., Mackay M., Aranow C., Davidson A. Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients JCI insight. 2018;3 doi: 10.1172/jci.insight.122525.
Jain S., Ba Z., Zhang Y., Dai H.Q., Alt F.W. CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning Cell. 2018;174:102-116.e14. doi: 10.1016/j.cell.2018.04.035.
Lin S.G., Ba Z., Alt F.W., Zhang Y. RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes Advances in Immunology. 2018;139:93-135. doi: 10.1016/bs.ai.2018.07.001.
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. doi: 10.4049/jimmunol.1602056.
Hernandez A., Holodick N. Editorial: Natural antibodies in health and disease Frontiers in Immunology. 2017;8(DEC) doi: 10.3389/fimmu.2017.01795.
Holodick N., Rodríguez-Zhurbenko N., Hernández A. Defining natural antibodies Frontiers in Immunology. 2017;8(JUL) doi: 10.3389/fimmu.2017.00872.
Kaku H., Holodick N., Tumang J., Rothstein T. CD25<sup>+</sup> B-1a cells express Aicda Frontiers in Immunology. 2017;8 doi: 10.3389/fimmu.2017.00672.
Martínez D., Pupo A., Cabrera L., Raymond J., Holodick N., Hernández A. B-CD8<sup>+</sup> T cell interactions in the anti-idiotypic response against a self-antibody Journal of Immunology Research. 2017;2017 doi: 10.1155/2017/2860867.
Cui X., Zhang L., Magli A., Catera R., Yan X., Griffin D., Rothstein T., Rothstein T., Rothstein T., Barrientos J., Barrientos J., Barrientos J., Kolitz J., Kolitz J., Kolitz J., Allen S., Allen S., Allen S., Rai K., Rai K., Rai K., Chiorazzi N., Chiorazzi N., Chiorazzi N., Chu C., Chu C., Chu C., Chu C. Cytoplasmic myosin-exposed apoptotic cells appear with caspase-3 activation and enhance CLL cell viability Leukemia. 2016;30(1):74-85. doi: 10.1038/leu.2015.204.
Guo B., Rothstein T. RasGRP1 is an essential signaling molecule for development of B1a cells with autoantigen receptors Journal of Immunology. 2016;196:2583-2590. doi: 10.4049/jimmunol.1502132.
Guo B., Zhang L., Chiorazzi N., Rothstein T. IL-4 rescues surface IgM expression in chronic lymphocytic leukemia Blood. 2016;128:553-562. doi: 10.1182/blood-2015-11-682997.
Holodick N., Vizconde T., Hopkins T., Rothstein T., Rothstein 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. doi: 10.4049/jimmunol.1600073.
Holodick N., Zeumer L., Rothstein T., Rothstein T., Rothstein T., Morel L. Expansion of B-1a cells with germline heavy chain sequence in lupus mice Frontiers in Immunology. 2016;7(MAR) doi: 10.3389/fimmu.2016.00108.
Kramer J.M., Kramer J.M., Kramer J.M., Kramer J.M., Holodick N.E., Vizconde T.C., Vizconde T.C., Raman I., Yan M., Li Q.Z., Gaile D.P., Rothstein T.L., 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. doi: 10.1189/jlb.2A0715-297R.
Lin S.G., Ba Z., Du Z., Zhang Y., Hu J., Alt F.W. Highly sensitive and unbiased approach for elucidating antibody repertoires Proceedings of the National Academy of Sciences of the United States of America. 2016;113:7846-7851. doi: 10.1073/pnas.1608649113.
Olofsson P., Olofsson P., Steinberg B., Steinberg B., Sobbi R., Cox M., Ahmed M., Oswald M., Szekeres F., Szekeres F., Hanes W., Introini A., Liu S., Holodick N., Rothstein T., Lövdahl C., Chavan S., Yang H., Pavlov V., Broliden K., Andersson U., Diamond B., Miller E., Arner A., Gregersen P., Backx P., Backx P., Mak T., Tracey K., Tracey K. Blood pressure regulation by CD4<sup>+</sup> lymphocytes expressing choline acetyltransferase Nature Biotechnology. 2016;34(10):1066-1071. doi: 10.1038/nbt.3663.
Pioli P., Whiteside S., Weis J., Weis J. Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs Immunobiology. 2016;221:618-633. doi: 10.1016/j.imbio.2016.01.007.
Quach T., Rodriguez-Zhurbenko N., Rodriguez-Zhurbenko N., Hopkins T., Guo X., Guo X., Hernandez A., Hernandez A., Li W., Rothstein T. Distinctions among circulating antibody-secreting cell populations, including B-1 cells, in human adult peripheral blood Journal of Immunology. 2016;196(3):1060-1069. doi: 10.4049/jimmunol.1501843.
Quách T., Hopkins T., Holodick N., Holodick N., Vuyyuru R., Vuyyuru R., Manser T., Bayer R., Rothstein T., Rothstein T., Rothstein T. 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. doi: 10.4049/jimmunol.1600630.
Rothstein T. Natural antibodies as rheostats for susceptibility to chronic diseases in the aged Frontiers in Immunology. 2016;7(APR) doi: 10.3389/fimmu.2016.00127.
Rothstein T., Rothstein T., Holodick N. Activation of B-1 Cells Encyclopedia of Immunobiology. 2016;3:237-243. doi: 10.1016/B978-0-12-374279-7.09021-4.
Sharma A., Kiripolsky J., Kiripolsky J., Klimatcheva E., Howell A., Fereidouni F., Levenson R., Rothstein T., Rothstein T., Rothstein T., Kramer J., Kramer J., Kramer J., Kramer J. Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction Clinical Immunology. 2016;164:85-94. doi: 10.1016/j.clim.2016.01.015.
Wang W., Org T., Montel-Hagen A., Pioli P.D., Duan D., Israely E., Malkin D., Su T., Flach J., Kurdistani S.K., Schiestl R.H., Mikkola H.K.A. MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis Nature Communications. 2016;7 doi: 10.1038/ncomms12376.
Aziz M., Holodick N., Rothstein T., Wang P., Wang P. The role of B-1 cells in inflammation Immunologic Research. 2015;63(1-3):153-166. doi: 10.1007/s12026-015-8708-3.
Engelbertsen D., Engelbertsen D., Vallejo J., Dan Quách T., Fredrikson G., Alm R., Hedblad B., Björkbacka H., Rothstein T., Nilsson J., Bengtsson E. Low levels of IgM antibodies against an advanced glycation endproduct-modified apolipoprotein B100 peptide predict cardiovascular events in nondiabetic subjects Journal of Immunology. 2015;195(7):3020-3025. doi: 10.4049/jimmunol.1402869.
Holodick N., Rothstein T., 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. doi: 10.1111/nyas.12825.
Hu J., Zhang Y., Zhao L., Frock R., Du Z., Meyers R., Meng F., Schatz D., Alt F. Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes Cell. 2015;163:947-959. doi: 10.1016/j.cell.2015.10.016.
Husain-Krautter S., Kramer J., Li W., Guo B., Rothstein T. The osteopontin transgenic mouse is a new model for Sjögren's syndrome Clinical Immunology. 2015;157:30-42. doi: 10.1016/j.clim.2014.12.010.
Lin S., Guo C., Sua A., Zhang Y., Alt F. CTCF-binding elements 1 and 2 in the Igh intergenic control region cooperatively regulate V(D)J recombination Proceedings of the National Academy of Sciences of the United States of America. 2015;112:1815-1820. doi: 10.1073/pnas.1424936112.
Pioli P., Chen X., Weis J., Weis J. Fatal autoimmunity results from the conditional deletion of Snai2 and Snai3 Cellular Immunology. 2015;295:1-18. doi: 10.1016/j.cellimm.2015.02.009.
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. doi: 10.1111/nyas.12949.
Rothstein T., Quach T. The human counterpart of mouse B-1 cells Annals of the New York Academy of Sciences. 2015;1362(1):143-152. doi: 10.1111/nyas.12790.