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
Khan N., Rothstein T.L. The Alternate Pathway for BCR Signaling Induced by IL-4 Requires Lyn Tyrosine Kinase Journal of Molecular Biology. 2021;433 doi: 10.1016/j.jmb.2020.10.002.
Hannibal M.C., Schwalm C., George N., Singh S.A., Rothstein T.L., Ludlow A., Glassford M., Udenberg K., Scott K. The Use of B-Cell Polysome Profiling to Validate Novel RPL5 (uL18) and RPL26 (uL24) Variants in Diamond-Blackfan Anemia Journal of Pediatric Hematology/Oncology. 2020 doi: 10.1097/MPH.0000000000001980.
Höfer T., Montecino-Rodriguez E., Pioli P.D., Rodewald H.R., Dorshkind K. Do haematopoietic stem cells age? Nature Reviews Immunology. 2020;20:196-202. doi: 10.1038/s41577-019-0236-2.
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.
Ludlow A.V., Gutknecht M.F., Rothstein T.L., Kaku H. 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.
Rothstein T.L., Kaku H. 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.
Rothstein T.L., Kaku H., Ludlow A.V., Gutknecht M.F. 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.
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.
Dorshkind K., Montecino-Rodriguez E., Morrison S.L., Pioli P.D., Casero D. 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.
Guo B., Brightwell A.S., Rothstein T.L., Ludlow A.V. 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.
Herzenberg L., Silverman G., Rothstein T., Montecino-Rodriguez E., Dorshkind K., Holodick N., Kantor A., Yang Y., Yoder M., Yoshimoto M., Ghosn E. B1 B cell progenitors Science. 2019;364:248. doi: 10.1126/science.aax6784.
Montecino-Rodriguez E., Kong Y., Rouault A., Dorshkind K., Pioli P.D., Casero 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.
Rodriguez-Zhurbenko N., Hopkins T.J., Quach T.D., 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.
Tsimikas S., Perry H.M., Upadhye A., Srikakulapu P., Gonen A., Hendrikx S., Nguyen A., McSkimming C., Marshall M.A., Garmey J.C., Taylor A.M., Bender T.P., Holodick N.E., Witztum J.L., McNamara C.A., Rothstein T.L. 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., Liang Z., Lou J., Kyritsis N., Dring E.W., Hu H., Zhang Y., Zurita J., Shamim M.S., Presser Aiden A., Lieberman Aiden E., Alt F.W., Ba Z. 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.
Zhang X., Zhang Y., Kyritsis N., Casellas R., Alt F.W., Ba Z. Fundamental roles of chromatin loop extrusion in antibody class switching Nature. 2019;575:385-389. doi: 10.1038/s41586-019-1723-0.
Aranow C., Davidson A., Liu Z., Byrne-Steele M., Quach T.D., Pan W., Yang Q., Mackay M., Leung T., Dascalu C., Han J., Lesser M., Huang W., Rothstein T.L., Furie R. Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients JCI insight. 2018;3 doi: 10.1172/jci.insight.122525.
Ba Z., Jain S., 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.
Ba Z., Lin S.G., 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.
Moreno-Merino P., Husain-Krautter S., Gallego J., Blanco E., Madeline Fagen E., 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.
Zhou M., Ochani M., Wang P., Aziz M., Ode Y., Holodick N., Rothstein T. B-1a cells protect mice from sepsis-induced acute lung injury Molecular Medicine. 2018;24 doi: 10.1186/s10020-018-0029-2.
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., Aziz M., 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.
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.
Pupo A., Cabrera L., Raymond J., Holodick N., Hernández A., Martínez D. 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.
Ba Z., Lin S.G., 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.
Cox M., Lövdahl C., Andersson U., Sobbi R., Ahmed M., Liu S., Broliden K., Gregersen P., Olofsson P., Olofsson P., Oswald M., Szekeres F., Szekeres F., Hanes W., Introini A., Holodick N., Rothstein T., Chavan S., Yang H., Pavlov V., Miller E., Arner A., Tracey K., Tracey K., Backx P., Backx P., Mak T., Steinberg B., Steinberg B., Diamond B. Blood pressure regulation by CD4<sup>+</sup> lymphocytes expressing choline acetyltransferase Nature Biotechnology. 2016;34(10):1066-1071. doi: 10.1038/nbt.3663.
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.
Hernandez A., Li W., Rothstein T., Quach T., Rodriguez-Zhurbenko N., Rodriguez-Zhurbenko N., Hopkins T., Guo X., Guo X., Hernandez A. 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.
Holodick N., Rothstein T., Rothstein T., Zeumer L., 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.
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., Vuyyuru R., Quách T., Hopkins T., Holodick N., 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.
Kiripolsky J., Kramer J., Kramer J., Sharma A., Kiripolsky J., Klimatcheva E., Howell A., Fereidouni F., Levenson R., Rothstein T., Rothstein T., Rothstein T., 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.
Li Q.Z., 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., 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.
Mikkola H.K.A., Duan D., Kurdistani S.K., Su T., Pioli P.D., Israely E., Schiestl R.H., Flach J., Malkin D., Org T., Montel-Hagen A., Wang W. MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis Nature Communications. 2016;7 doi: 10.1038/ncomms12376.
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., Holodick N., Rothstein T. Activation of B-1 Cells Encyclopedia of Immunobiology. 2016;3:237-243. doi: 10.1016/B978-0-12-374279-7.09021-4.
Whiteside S., Pioli P., 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.
Zhang L., Cui X., Kolitz J., Chu C., Chu C., Magli A., Catera R., Yan X., Griffin D., Rothstein T., Rothstein T., Rothstein T., Barrientos J., Barrientos J., Barrientos 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. 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.
Alt F.W., Meng F.L., Schatz D.G., Meyers R.M., Du Z., Hu J., Zhang Y., Zhao L., Frock R.L. Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes Cell. 2015;163:947-959. doi: 10.1016/j.cell.2015.10.016.
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.
Holodick N., Wang P., Aziz M., Rothstein T., 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.
Kramer J.M., Rothstein T.L., Li W., Guo B., Husain-Krautter S. 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.
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.
Vallejo J., Fredrikson G., Engelbertsen D., Engelbertsen D., Dan Quách T., 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.
Weis J., Weis J., Pioli P., Chen X. 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.
Zhang Y., Sua A., Lin S., Guo C., 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.