Ellen R. Richie, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
A major focus of my research program is to discern the molecular pathways that regulate thymus development and homeostasis. T cell development requires indispensable growth, survival and differentiation signals supplied by thymic epithelial cells (TECs) in the stromal microenvironment. Loss of TECs during age-associated or cytoablative therapy-induced thymus involution reduces thymopoiesis and naive T cell output. The resulting restriction in T cell receptor repertoire diversity of peripheral T cells severely compromises immune responses to newly encountered antigens. We are using various transgenic and knock-out experimental models to identify molecular pathways that can be manipulated to prevent or reverse thymus involution in order to maintain protective T cell immune responsiveness. In another approach to provide a functional thymic microenvironment, we are studying the molecular pathways that commit primitive endodermal progenitors to a TEC fate and regulate differentiation of functional TEC subsets.
We are also investigating the genetic and epigenetic pathways that regulate thymocyte differentiation and thymic lymphoma development. Using an experimental model in which thymic lymphomas are induced by injecting the carcinogen N-methyl-N-nitrosourea (MNU), we have shown that mice expressing a hypomorphic allele of the Polycomb group gene eed have a partial block in thymocyte differentiation as well as enhanced susceptibility to MNU-induced lymphomagenesis. These data suggest that eed functions as a tumor suppressor gene in inhibiting thymic lymphoma. We are currently investigating the mechanisms by which eed regulates T cell development and lymphomagenesis.
Education & Training
Degree-Granting Education
| 1970 | The University of Texas, Austin, TX, USA, PHD, Immunochemistry |
| 1967 | The University of Texas, Austin, TX, USA, BA, Microbiology-major, Chemistry and English-minors |
Postgraduate Training
| 1970-1972 | Research Fellowship, Baylor College of Medicine, Division of Experimental Biology, Houston, TX |
Experience & Service
Academic Appointments
Associate Professor, Division of Science Park-Research Division, The University of Texas System Cancer Center, Smithville, TX, 1982 - 1991
Associate Professor, Department of Pediatrics, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, TX, 1979 - 1982
Assistant Professor, Department of Pediatrics, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, TX, 1974 - 1979
Assistant Professor, Division of Experimental Biology, Baylor College of Medicine, Houston, TX, 1972 - 1974
Administrative Appointments/Responsibilities
Assistant Dean, The University of Texas Health Science Center at Houston, Graduate School of Biomedical Sciences, Houston, TX, 1983 - 2021
Other Appointments/Responsibilities
Member, American Association of Immunologists Finance Subcommittee, Bethesda, MD, 2005 - 2008
Institutional Committee Activities
Program Director, Molecular Carcinogenesis Program, The University of Texas Health Science Center at Houston, The Graduate School of Biomedical Sciences, Houston, Texas, 1999 - 2010
Chairperson, Postdoctoral Training Committee, The University of Texas System Cancer Center, Science Park, 1984 - Present
Honors & Awards
| 2011 | Reappointed to the GSBS Faculty with Commendation |
| 2006 | Reappointed to the GSBS Faculty with Commendation |
| 2001 | Reappointed to the GSBS Faculty with Commendation |
| 2000 | M. D. Anderson Educator of the Month |
| 1998 | M.D. Anderson Cancer Center Faculty Achievement Award in Education |
Selected Publications
Peer-Reviewed Articles
- Srinivasan J, Vasudev A, Shasha C, Selden HJ, Perez E, LaFleur B, Sinari SA, Krueger A, Richie ER, Ehrlich LIR. The initial age-associated decline in early T-cell progenitors reflects fewer pre-thymic progenitors and altered signals in the bone marrow and thymus microenvironments. Aging Cell 22(8):e13870, 2023. e-Pub 2023. PMID: 37221658.
- Gencel-Augusto J, Su X, Qi Y, Whitley EM, Pant V, Xiong S, Shah V, Lin J, Perez E, Fiorotto ML, Mahmud I, Jain AK, Lorenzi PL, Navin NE, Richie ER, Lozano G. Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program. Cancer Discov 13(5):1230-1249, 2023. PMID: 37067911.
- Lancaster JN, Keatinge-Clay DE, Srinivasan J, Li Y, Selden HJ, Nam S, Richie ER, Ehrlich LIR. Central tolerance is impaired in the middle-aged thymic environment. Aging Cell 21(6):e13624, 2022. e-Pub 2022. PMID: 35561351.
- Singarapu N, Ma K, Reeh KAG, Shen J, Lancaster JN, Yi S, Xie H, Orkin SH, Manley NR, Ehrlich LIR, Jiang N, Richie ER. Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment. Sci Rep 8(1):14335, 2018. e-Pub 2018. PMID: 30254371.
- Zhu F, Willette-Brown J, Song NY, Lomada D, Song Y, Xue L, Gray Z, Zhao Z, Davis SR, Sun Z, Zhang P, Wu X, Zhan Q, Richie ER, Hu Y. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis. Cell Host Microbe 21(4):478-493.e7, 2017. PMID: 28407484.
- Gomes AC, Hara T, Lim VY, Herndler-Brandstetter D, Nevius E, Sugiyama T, Tani-ichi S, Schlenner S, Richie E, Rodewald H-R, Flavell RA Nagasawa T, Ikuta K, Pereira JP. Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation. Immunity 45(6):1219-1231, 2016.
- Bain VE, Gordon J, O'Neil JD, Ramos I, Richie ER, Manley NR. Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate. Development 143(21):4027-4037, 2016. e-Pub 2016. PMID: 27633995.
- Lomada D, Jain M, Bolner M, Reeh KA, Kang R, Reddy MC, DiGiovanni J, Richie ER. Stat3 Signaling Promotes Survival and Maintenance of Medullary Thymic Epithelial Cells. PLoS Genet 12(1):e1005777, 2016. e-Pub 2016. PMID: 26789196.
- Reeh KA, Cardenas KT, Bain VE, Liu Z, Laurent M, Manley NR, Richie ER. Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis. Development 141(15):2950-8, 2014. PMID: 25053428.
- Williams JA, Zhang J, Jeon H, Nitta T, Ohigashi I, Klug D, Kruhlak MJ, Choudhury B, Sharrow SO, Granger L, Adams A, Eckhaus MA, Jenkinson SR, Richie ER, Gress RE, Takahama Y, Hodes RJ. Thymic medullary epithelium and thymocyte self-tolerance require cooperation between CD28-CD80/86 and CD40-CD40L costimulatory pathways. J Immunol 192(2):630-40, 2014. e-Pub 2013. PMID: 24337745.
- Garfin PM, Min D, Bryson JL, Serwold T, Edris B, Blackburn CC, Richie ER, Weinberg KI, Manley NR, Sage J, Viatour P. Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression. J Exp Med 210(6):1087-97, 2013. e-Pub 2013. PMID: 23669396.
- Li J, Zhao Z, Carter C, Ehrlich LI, Bedford MT, Richie ER. Coactivator-Associated Arginine Methyltransferase 1 Regulates Fetal Hematopoiesis and Thymocyte Development. J Immunol 190(2):597-604, 2013. e-Pub 2012. PMID: 23248263.
- Bryson JL, Griffith AV, Hughes B, Saito F, Takahama Y, Richie ER, Manley NR. Cell-Autonomous Defects in Thymic Epithelial Cells Disrupt Endothelial-Perivascular Cell Interactions in the Mouse Thymus. PLoS One 8(6):e65196, 2013. e-Pub 2013. PMID: 23750244.
- Onder L, Narang P, Scandella E, Chai Q, Iolyeva M, Hoorweg K, Halin C, Richie E, Kaye P, Westermann J, Cupedo T, Coles M, Ludewig B. IL-7-producing stromal cells are critical for lymph node remodeling. Blood 120(24):4675-83, 2012. e-Pub 2012. PMID: 22955921.
- Badeaux AI, Yang Y, Cardenas K, Vemulapalli V, Chen K, Kusewitt D, Richie E, Li W, Bedford MT. Loss of the methyl-lysine effector molecule PHF20 impacts the expression of genes regulated by the lysine acetyltransferase MOF. J Biol Chem 287(1):429-37, 2012. e-Pub 2011. PMID: 22072714.
- Manley NR, Richie ER, Blackburn CC, Condie BG, Sage J. Structure and function of the thymic microenvironment. Frontiers in Bioscience 16:2461-2477, 2011.
- Foster KE, Gordon J, Cardenas K, Veiga-Fernandes H, Makinen T, Grigorieva E, Wilkinson DG, Blackburn CC, Richie E, Manley NR, Adams RH, Kioussis D, Coles MC. EphB-ephrin-B2 interactions are required for thymus migration during organogenesis. Proc Natl Acad Sci U S A 107(30):13414-9, 2010. e-Pub 2010. PMID: 20616004.
- Kim D, Lee J, Cheng D, Li J, Carter C, Richie E, Bedford MT. Enzymatic activity is required for the in vivo functions of CARM1. J Biol Chem 285(2):1147-52, 2010. e-Pub 2009. PMID: 19897492.
- Rojas P, Benavides F, Blando J, Perez C, Cardenas K, Richie E, Knudsen ES, Johnson DG, Senderowicz AM, Rodriguez-Puebla ML, Conti CJ. Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b). Mol Carcinog 48(6):508-16, 2009. PMID: 18942117.
- Repass JF, Laurent MN, Carter C, Reizis B, Bedford MT, Cardenas K, Narang P, Coles M, Richie ER. IL7-hCD25 and IL7-Cre BAC transgenic mouse lines: New tools for analysis of IL-7 expressing cells. Genesis 47(4):281-7, 2009. PMID: 19263498.
- Griffith AV, Cardenas K, Carter C, Gordon J, Iberg A, Engleka K, Epstein JA, Manley NR, Richie ER. Increased thymus- and decreased parathyroid-fated organ domains in Splotch mutant empryos. Dev Biol 327(1):216-27, 2009. e-Pub 2008. PMID: 19135046.
- Lomada D, Liu B, Coghlan L, Hu Y , Richie ER. Thymus medulla formation and central tolerance are restored in IKKalpha-/- mice that express an IKKalpha transgene in keratin 5+ thymic epithelial cells. J Immunol 178(2):829-37, 2007. PMID: 17202344.
- Benavides F, Gomez G, Venables-Griffith A, Lambertz I, Flores M, Angel JM, Fuchs-Young R, Richie ER, Conti CJ. Differential susceptibility to chemically induced thymic lymphomas in SENCARB and SSIN inbred mice. Mol Carcinog 45(7):543-8, 2006. PMID: 16479612.
- Zamisch M, Moore-Scott B, Su DM, Lucas PJ, Manley N, Richie ER. Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol 174(1):60-7, 2005. PMID: 15611228.
- El Kassar N, Lucas PJ, Klug DB, Zamisch M, Merchant M, Bare CV, Choudhury B, Sharrow SO, Richie E, Mackall CL, Gress RE. A dose effect of IL-7 on thymocyte development. Blood 104(5):1419-27, 2004. PMID: 15155461.
- Kim J, Lee J, Yadav N, Wu Q, Carter C, Richard S, Richie E, Bedford MT. Loss of CARM1 results in hypomethylation of thymocyte cyclic AMP-regulated phosphoprotein and deregulated early T cell development. J Biol Chem 279(24):25339-44, 2004. PMID: 15096520.
- Benavides F, Zamisch M, Flores M, Campbell MR, Andrew SE, Angel JM, Licchesi J, Sternik G, Richie ER, Conti CJ. Application of inter-simple sequence repeat PCR to mouse models: assessment of genetic alterations in carcinogenesis. Genes Chromosomes Cancer 35(4):299-310, 2002. PMID: 12378524.
- Klug DB, Carter C, Gimenez-Conti IB, Richie ER. Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus. J Immunol 169(6):2842-5, 2002. PMID: 12218095.
- Angel JM, Richie ER. Tlag2, an N-methyl-N-nitrosourea susceptibility locus, maps to mouse chromosome 4. Mol Carcinog 33(2):105-12, 2002. PMID: 11813303.
- Richie ER, Schumacher A, Angel JM, Holloway M, Rinchik EM, Magnuson T. The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas. Oncogene 21(2):299-306, 2002. PMID: 11803473.
- Benavides F, Venables A, Poetschke Klug H, Glasscock E, Rudensky A, Gomez M, Martin Palenzuela N, Guenet JL, Richie ER, Conti CJ. The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (CtsI) gene. Immunogenetics 53(3):233-42, 2001. PMID: 11398968.
- Poetschke HL, Klug DB, Perkins SN, Wang TT, Richie ER, Hursting SD. Effects of calorie restriction on thymocyte growth, death and maturation. Carcinogenesis 21(11):1959-64, 2000. PMID: 11062154.
- Richie ER, Walker DA. Production and characterization of immature murine T-lymphoma cell lines. Methods Mol Biol 134:177-84, 2000. PMID: 10730257.
- Rodriguez-Puebla ML, LaCava M, Miliani De Marval PL, Jorcano JL, Richie ER, Conti CJ. Cyclin D2 overexpression in transgenic mice induces thymic and epidermal hyperplasia whereas cyclin D3 expression results only in epidermal hyperplasia. Am J Pathol 157(3):1039-50, 2000. PMID: 10980142.
- Gomez G, Clarkin KZ, Kraig E, Infante AJ, Richie ER. TCR v(beta) repertoire restriction and lack of CDR3 conservation implicate TCR-superantigen interactions in promoting the clonal evolution of murine thymic lymphomas. Int Immunol 12(3):263-70, 2000. PMID: 10700461.
- Klug DB, Crouch E, Carter C, Coghlan L, Conti CJ, Richie ER. Transgenic expression of cyclin D1 in thymic epithelial precursors promotes epithelial and T cell development. J Immunol 164(4):1881-8, 2000. PMID: 10657637.
- Klug DB, Carter C, Crouch E, Roop D, Conti CJ, Richie ER. Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc Natl Acad Sci U S A 95(20):11822-7, 1998. PMID: 9751749.
Invited Articles
- Srinivasan J, Lancaster JN, Singarapu N, Hale LP, Ehrlich LIR, Richie ER. Age-related changes in thymic central tolerance. Front Immunol 12:676236, 2021. e-Pub 2021. PMID: 33968086.
Book Chapters
- Nowell CS, O'Neill K, Rouse P, Henderson T, Richie ER, Manley NR, Blackburn CC. Thymus and Parathyroid Organogenesis. In: Principles of Tissue Engineering, 2020.
- O'Neill K, Nowell CS, Richie E, Manley NR, Blackburn CC. Thymus and Parathyroid Organogenesis. In: Principles of Tissue Engineering, 2016.
- Bain V, Richie ER. Identifying the spatial relationships of thymic stromal and thymocyte subsets by immunofluorescence analysis. In: Methods Mol Biol, 75-85, 2016.
- Manley NR, Richie ER, Blackburn CC, Condie BG, Sage J. Structure and function of the thymic microenvironment. In: Front Biosci (Landmark Ed), 2461-77, 2011.
- Nowell CS, Richie E, Manley NR, Blackburn CC. Thymus and parathyroid organogenesis. In: Principles of Tissue Engineering. 3. Elsevier/Academic Press: Burlington MA, 647-62, 2008.
- Richie ER, Walker DA. Production and characterization of immature murine T-lymphoma cell lines. In: T Cell Protocols: Development and Activation. Methods in Molecular Biology, Volume 134. Humana Press, 177-84, 2000.
- Richie ER, Angel JM, Rinchik EM. Tlag1, a novel murine tumor susceptibility gene that regulates MNU-induced thymic lymphoma development. In: Genetics and Susceptibility: Impact on Risk Assessment. Wiley Liss, 23-32, 1996.
Patient Reviews
CV information above last modified June 27, 2024