Lauren I EhrlichAssistant Professor
Molecular BiosciencesThymocyte: stromal cell interactions in T cell development and T-ALLlehrlich@austin.utexas.edu
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
Austin, TX 78712
T cells are master regulators of the adaptive immune system: they are essential for coordinating the appropriate immune response to different pathogens, and they are responsible for immunologic memory, which protects us from recurrent infections. As T cells develop in the thymus, they encounter a wide variety of cells in their microenvironment, collectively referred to as the thymic stroma. Thymocytes and stromal cells are mutually dependant on each other for proper development and maintenance. Deviations in normal thymocyte: stromal interactions are thought to contribute to diseases such as T cell lymphoma and autoimmunity. Our lab utilizes live cell 2-photon microscopy to study the dynamic cellular and molecular interactions between thymocytes and stromal cells that promote normal T cell development, resulting in a healthy T cell repertoire. In addition, we seek to identify tumor:stromal interactions that promote T-ALL progression and/or persistence. By using two-photon live-cell imaging, we will query the dynamics of molecular and cellular interactions in tumor development within an intact three-dimensional organ. Since we will compare thymocyte: stromal interactions that occur throughout normal thymocyte development with those that occur during lymphomagenesis, using both imaging and microarray analyses, we will be able to identify aberrant molecular interactions as potential therapeutic targets. By blocking such tumor: stromal interactions, we will strive to inhibit essential events in tumor progression. Ultimately, we hope this work will contribute to the development of lower toxicity therapeutics to significantly improve T-ALL treatment and disease outcome.
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. Published online September 28, 2015. DOI 10.1084/jem.20150178.
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 394M