My laboratory’s major research goals are to identify the cellular and molecular interactions between developing T cells and the surrounding thymic stromal cells that govern generation of a diverse, non-autoreactive, and non-malignant T cell pool throughout the lifespan. 

We employ a variety of experimental approaches to investigate T cell development in mouse models. We use time-lapse two-photon microscopy to investigate thymocyte:stromal cell interactions in live tissue, single-cell and bulk transcriptional profiling of thymocyte and stromal cell subsets to identify candidate genes that impact T cell differentiation or tumorigenesis, multi-parameter flow cytometric and multiplex immunofluorescent analyses of lymphoid tissues from  genetic mouse models to assess the impact of different genes on thymic function, thymocyte development and tumorigenesis, and in vitro assays to assess the impact of genes/pathways on lymphocyte activation and leukemia survival and growth. 

We are also currently investigating immune correlates of disease severity in COVID-19 patients across the lifespan. In keeping with our interests in understanding the delicate balance between maintaining a diverse repertoire while avoiding autoimmunity, we are also studying links between SARS-CoV-2 infection and autoimmunity.

The Ehrlich lab is currently focused on:

• Identifying cellular and molecular mechanisms, such as chemokine-driven chemotaxis, that contribute to T cell self-tolerance by promoting thymocyte medullary entry and/or interactions with antigen presenting cells
• Determining how age-associated changes in the thymus throughout the lifespan impact thymic stromal cellularity and function, thymocyte development, and the establishment of central tolerance
• Identifying molecular mediators of interactions between T cell acute lymphoblastic leukemia cells and the surrounding tumor microenvironment that promote leukemia growth
• Identifying variation in immune responses in COVID-19 patients across the lifespan (pediatric to geriatric) that correlate with differential disease severity
• Determining if SARS-CoV-2 infections predispose patients to autoimmunity

Publications:

2020 Spencer C. Wei, Wouter C. Meijers, Nana-Ama A.S. Anang, Margaret L. Axelrod, Elles M. Screever, Douglas Johnson, Lorenz Lehmann, Pierre-Yves Courand, Elizabeth M. Whitley, James J. Mancuso, Lauren Himmel, Matthew Wlekinski, Bjorn Knollmann, Yu Li, Jayashree Srinivasan, Oluwatomisin T. Atolagbe, Xiayu Rao, Yang Zhao, Jing Wang, Lauren I. R. Ehrlich, Joe-Elie Salem, Justin Balko, Javid J. Moslehi, and James P. Allison. CTLA-4 and PD-1 Interact in Immune Checkpoint Blockade-Induced Myocarditis. Cancer Discovery. In press

2020 Triplett TA*, Nam SH, Hu Z, Arasappan D, Godfrey WH, Ames RY, Sarang A, Selden HJ, Lee C-H, Georgiou G, Horton TM, Ehrlich LIR. Blood.136(16):1837–50

2020 Warden AS, Triplett TA, Lyu A, Grantham EK, Azzam MM, DaCosta A, Mason S, Blednov YA, Ehrlich LIR, Mayfield DR, and Harris RA. Microglia depletion and alcohol: Transcriptome and behavioral profiles. Addiction Biology. 29(4):e12889

2019 Lancaster JN, Thyagarajan HM, Srinivasan J, Li Y, Hu Z, Ehrlich LIR. Live-cell imaging reveals the relative contributions of antigen presenting cell subsets to thymic central tolerance. Nature Communications.10(1):2220. PMCID: PMC6525199

2019 Jarrett AM, BloomM, GodfreyW, SyedA, EkrutDA, EhrlichLIR, YankeelovTE, SoraceAG. Mathematical modeling of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer.  Mathematical Medicine and Biology. 15:730. PMID 30239754  

2018 Singarapu N, Ma K, Reeh KAG, Shen J, Lancaster JN, Xie H, OrkinS , Manley NR, Ehrlich LIR, Jiang N, Richie ER. Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment. Scientific Reports. 8(1):14335. PMCID: PMC6156232

2018 Triplett TA, Garrison KC, Marshall N, Donkor M, Blazeck J, LambC, QerqezA, Dekker JD, TannoY, Lu WC, Karamitros CS, Ford K, TanB, ZhangM, McGovern K, Coma S, KumadaY, Yamany MS, Sentandreu E, Fromm G, TizianiS, Schreiber TH, Manfredi M, Ehrlich LIR, Stone E,and Georgiou G. (2018) Reversal of IDO-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme.Nature Biotechnology.36 (8):758-764. PMCID:PMC6078800

2018 Thyagarajan HM, Lancaster JN, Lira SA, Ehrlich LIR. CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction. PLoS ONE. 13(7):e0200765. PMCID: PMC6053179

2017 LancasterJN, Li Y, Ehrlich LIR. Chemokine-mediated choreography of thymocyte development and selection.Trends in Immunology. PMCID PMC5800975

2017 Hu Z*, Li Y*, van Nieuwenhuijze A, Selden HJ, Kessler R, Liston A, Ehrlich LIR. CCR7 modulates the capacity of thymic dendritic cells to induce regulatory T cells. Cell Reports.21(1):168–80. PMCID: PMC5639943

2017 Ki S*, Thyagarajan HM*, Hu Z, Lancaster JN, and Ehrlich LIR. EBI2 contributes to the induction of thymic central tolerance in mice by promoting rapid motility of medullary thymocytes. EurJ Immunol,14:377. PMCID: PMC5944344

2017 Lancaster JN and Ehrlich LIR. Analysis of Thymocyte Migration, Cellular Interactions, and Activation by Multiphoton Fluorescence Microscopy of Live Thymic Slices. Methods Mol Biol: 1591:9–25.(Chapter 2):9–25. PMID: 2834947

2016 Hu Z, Lancaster JN, Ehrlich LIR*, and Mueller P*. (2016) Detecting T Cell Activation Using a Varying Dimension Bayesian Model. Journal of Applied Statistics.Epub 2017 Feb 16. PMCID: PMC5796679

2016 Nath S, Christian L, Tan SY, Ki S, Ehrlich LIR, Poenie M. Dynein separately partners with NDE1 and dynactin to orchestrate T cell focused secretion. J Immunol. 197 (6): 2090-2101. PMCID PMC50109902

2016 Ehrlich LIR. Control of migration during intrathymic T cell development. In Ratcliffe MJH (Editor in Chief), Encyclopedia of Immunobiology. Vol.1, pp. 249-262. Oxford: Academic Press

2016 Triplett TA, Cardenas KT, Lancaster JN, Hu Z, Selden HJ, Jasso G, Balasubramanyam S, Chan K, Li L, Chen X, Marcogliese AM, Dave UP, Love PE, and Ehrlich LIR. Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. Proc. Natl. Acad. Sci. USA. 113(8): E1016-25. PMCID PMC4776467

2015 Hu Z, Lancaster JN, Sasiponganan C, Ehrlich LIR. CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance. Journal of Experimental Medicine.212 (11):1947-1965. PMCID PMC4612092

2015 Hu Z, Lancaster JN, Ehrlich LIR. The contribution of chemokines and migration to the induction of central tolerance in the thymus. Frontiers in Immunology. 6: 398 DOI:10.3389/fimmu.2015.00398.

2014 Brown KA, Yang X, Schipper D, Hall JW, DePue LJ, Gnanam AJ, Arambula JF, Jones JN, Swaminathan J, Dieye Y, Vadivelu J, Chandler DJ, Marcotte EM, Sessler JL, Ehrlich LIR, Jones RA. A self-assembling lanthanide molecular nanoparticle for optical imaging. Dalton Transactions. 44(6):2667-2675. PMID 25512085

2014 Ki S*, Park D*, Selden HJ, Seita J, Chung H, Kim J, Iyer VR, Ehrlich LIR.  Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution. Cell Reports. 9:402-415. PMID 25284794

2014 Jones RA, Gnanam AJ, Arambula JF, Jones JN, Swaminathan J, Yang X, Schipper D, Hall JW, DePue LJ, Dieye Y, Vadivelu, J, Chandler DJ, Marcotte EM, Sessler JL, Ehrlich LIR, Brown KA.  Lanthanide nano-drums: A new class of molecular nanoparticles for potential biomedical applications. Faraday Discussions. 175:241-255.

2014 Norrie JL, Lewandowski JP, Bouldin CM, Amarnath SR, Li Q, Vokes MS, Ehrlich LIR, Harfe BD, and Vokes SA.  Dynamics of BMP signaling in limb bud mesenchyme and polydactyly. Developmental Biology. 393 (2):270-281.

2012 LiJ, ZhaoZ, Carter C, Ehrlich LIR*, Bedford MT*, Richie ER*. CARM1 regulates fetal hematopoiesis and thymocyte development J Immunol. 190(2):597-604.

2011 Seita J, Sahoo D, Rossi DJ, Battacharya D, Serwold T, Inlay MA, Ehrlich LIR, Fathman JW, Dill DL, Weissman IL, Gene Expression Commons: an open platform for definitive gen expression profiling. PLOS One 7 (7): e40321

2011 Ehrlich LIR*, Serwold T*, Weissman IL., In vitro assays misrepresent in vivo linage potentials of murine lymphoid progenitors. Blood 117: 2618-24

2010 Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee, MJ, Ji H, Ehrlich LIR , Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, Mckinney-Freeman S, Naveiras O, Yoon T, Irizarry RA, Hanna J, Jaenisch R, Weissleder R, Orkin S, Weissman IL, Feinberg AP*, and Daley GQ*., Epigenetic memory in induced pluripotent stem cells. Nature 467: 285-90

2010 Ji H*, Ehrlich LIR*, Seita J*, Doi A*, Lee H, Lindau P, Murakami P, Aryee M, Rossi DJ, Inlay MA, Serwold T, Karsunky H, Ho L, Weissman IL, and Feinberg AP., A comprehensive epigenome map of lineage-specific hematopoiesis. Nature 467: 338-42

2009 Serwold TS*, Ehrlich LIR*, Weissman IL., Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis. Blood 113: 807-15

2009 Ehrlich LIR*, Oh DY*, Weissman IL, and Lewis RS., Differential contribution of chemotaxis and substrate restriction to segregation of immature and mature thymocytes. Immunity 31: 986-998

2008 Bhatacharrya D, Ehrlich LIR, and Weissman IL., Space-time considerations for hematopoietic stem cell transplantation., Eur J Immunol 38: 2060-7

2008 Ebert PJR, Ehrlich LIR, and Davis MM., Ligand Requirements and Synapse Formation in Thymic Selection., Immunity 29: 734-45

2003 Kuhne MR, Lin J, Yablonski D, Mollenauer MN, Ehrlich LIR, Huppa J, Davis MM, and Weiss A., Linker for Activation of T Cells, Zeta-Associated Protein-70, and Src Homology 2 Domain-Containing Leukocyte Protein-76 are Required for TCR-Induced Microtubule- Organizing Center Polarization. J Immunol 171: 860-866

2003 Davis MM, Krogsgaard M, Huppa JB, Sumen C, Prubhoo MA, Irvine DJ, Wu LC, and Ehrlich L., Dynamics of Cell Surface Molecules During T cell Recognition. Ann Rev Biochem 72: 717-742

2002 Richie LI, Ebert PJR, Wu LC, Krummel MF, Owen JT, Davis MM., Imaging synapse formation during thymocyte selection: inability of CD3zeta to form a stable central accumulation during negative selection., Immunity 16: 595-606

2002 Ehrlich LIR, Krummel MF, Weiss A, Davis MM., Dynamics of p56lck Translocation to the T Cell Immunological Synapse following Agonist and Antagonist Stimulation., Immunity 17: 809-822

* Denotes equal contribution

Introduction to Immunology Bio360K/ Bio 394L