Gregory C IppolitoResearch Assistant Professor
Molecular BiosciencesNormal and malignant B-cell immunology. Antibody email@example.com
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
Austin, TX 78712
Dr. Ippolito initially studied physics at Reed College and then completed training in B-cell immunology at The University of Alabama at Birmingham, The University of Cologne (Germany), and The University of Texas at Austin. Key areas of research have focused upon normal and malignant B-cell immunology, immune-based animal modeling, and antibody repertoires. This has included (1) in vivo study of globally altered antibody repertoires and B-cell function in gene-targeted mice; (2) generation of conditional knockout mice for the characterization of the Bcl11a and Foxp1 proto-oncogenes crucial for B-cell biology; and (3) directorship of the preclinical development of a therapeutic human monoclonal antibody presently in pivotal Phase III clinical trials.
Current research with Dr. George Georgiou utilizes state-of-the-art molecular and proteomic techniques for the "deep" profiling of humoral immunity and human antibody repertoires. The group has developed, published, and patented technologies for the extensive molecular analysis of antibody responses, whether elicited by vaccination or natural infection, which allow for the direct comparison of protein-level serum antibody repertoires to DNA-level repertoires in circulating peripheral blood B cells -- a unique description that is yielding fresh insights into the temporal dynamics and sequence composition of adaptive humoral immunity.
Two key technologies, BCR-Seq and Ig-Seq, are used in concert to gather immune response data that is then subjected to bioinformatic analysis.
1. BCR-Seq: Short for “B-cell repertoire sequencing,” this technology allows for analysis of a patient’s immune response at the single-cell level by analyzing the antibody information presented on the surface of the many thousands of individual B-cells produced in response to vaccination or infection.
2. Ig-Seq: Short for “Immunoglobulin sequencing,” this second technology is a proteomic/informatics strategy that, when combined with BCR-Seq data, enables determination of molecular-level identification and functionality of the most prevalent immune response antibody proteins (immunoglobulins) in blood or other fluids.
3. Bioinformatic analysis: A complex set of statistical and computational methods are used to analyze BCR-Seq and Ig-Seq data. This enables researchers to identify specific factors that impart immunological protection against disease.
2016 Woodworth MB, Greig LC, Liu KX, Ippolito GC, Tucker HO, Macklis JD, Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers, Cell Rep S2211-1247(16)30335-7. doi: 10.1016/j.celrep.2016.03.064
2016 DeKosky BJ, Lungu OI, Park D, Johnson EL, Charab W, Chrysostomou C, Kuroda D, Ellington AD, Ippolito GC, Gray JJ, Georgiou G, Large-Scale Sequence and Structural Comparisons of Human Naïve and Antigen-Experienced Antibody Repertoires, Proc Natl Acad Sci USA doi: 10.1073/pnas.1525510113
2016 Dekker JD, Park D, Shaffer AL III, Kohlhammer H, Deng W, Lee B-K, Ippolito GC, Georgiou G, Iyer VR, Staudt LM, Tucker HO, Subtype Specific Addiction of the Activated B Cell Subset of Diffuse Large B Cell Lymphoma to FOXP1, Proc Natl Acad Sci USA doi: 10.1073/pnas.1524677113
2015 Wine Y, Horton AP, Ippolito GC, Georgiou G, Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire, Curr Opin Immunol 35:89-97.
2015 Silva-Sanchez A, Liu CR, Vale AM, Khass M, Kapoor P, Elgavish A, Ivanov II, Ippolito GC, Schelonka RL, Schoeb TR, Burrows PD, Schroeder HW Jr., Violation of an Evolutionarily Conserved Immunoglobulin Diversity Gene Sequence Preference Promotes Production of dsDNA-Specific IgG Antibodies, PLoS ONE 10(2):e0118171
2015 Lavinder JJ, Horton AP, Georgiou G, Ippolito GC, Next-generation sequencing and protein mass spectrometry for the comprehensive analysis of human cellular and serum antibody repertoires, Current Opinion in Chemical Biology 24C:112-120.
2015 DeKosky BJ, Kojima T, Rodin A, Charab W, Ippolito GC, Ellington AD, Georgiou G, In-Depth Determination and Analysis of the Human Paired Heavy and Light Chain Antibody Repertoire, Nature Medicine 21(1):86-91
2014 Szymanska Mroczek E, Ippolito GC, Rogosch T, Hoi K-H, Hwangpo TA, Brand MG, Zhuang Y, Liu CR, Schneider DA, Zemlin M, Brown E, Georgiou G, Schroeder HW Jr, Differences in the composition of the human antibody repertoire by B cell subsets in the blood, Front Immunol 5:96
2014 Ippolito GC*, Dekker JD*, Wang Y-H, Lee B-K, Shaffer AL III, Lin J, Wall JK, Lee B-S, Staudt LM, Liu Y-J, Iyer VR, Tucker HO, Dendritic cell fate is determined by BCL11A, Proc Natl Acad Sci USA (*co-first authors) doi:10.1073/pnas.1319228111
2014 Steiniger SCJ, Dunkle WE, Bammert GF, Wilson TL, Krishnan A, Dunham SA, Ippolito GC, Bainbridge G, Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice, Mol Immunology 59: 71-78
2014 Lavinder J, Wine Y, Giesecke C, Ippolito GC, Horton AP, Hoi K-H, DeKosky BJ, Ellington AD, Dörner T, Marcotte EM, Boutz DR, Georgiou G, Identification and characterization of the constituent human serum antibodies elicited by vaccination, Proc Natl Acad Sci USA 111(6):2259-64 doi/10.1073/pnas.1317793111
2014 Georgiou G, Ippolito GC, Beausang J, Busse CE, Wardemann H, Quake SR, The promise and challenge of high-throughput sequencing of the antibody repertoire, Nat Biotechnol 32(2): 1-11
2013 Hoi KH, Ippolito GC, Intrinsic bias and public rearrangements in the human immunoglobulin Vλ light chain repertoire, Genes Immunity 14(4):271-6
2013 Lee BS, Dekker JD, Lee BK, Iyer VR, Sleckman BP, Shaffer AL 3rd, Ippolito GC, Tucker PW, The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination, Mol Cell Biol 33(9):1768-81
2013 DeKosky BJ, Ippolito GC, Deschner RP, Lavinder JJ, Wine Y, Rawlings BM, Varadarajan N, Giesecke C, Dörner T, Andrews SF, Wilson PC, Hunicke-Smith SP, Willson CG, Ellington AD, Georgiou G, High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire, Nat Biotechnol 31(2):166-9
2012 Rogosch T, Kerzel S, Hoi KH, Zhang Z, Maier RF, Ippolito GC, Zemlin M, Immunoglobulin analysis tool: a novel tool for the analysis of human and mouse heavy and light chain transcripts, Front Immunol 3:176
2012 Ippolito GC, Hoi KH, Reddy ST, Carroll SM, Ge X, Rogosch T, Zemlin M, Shultz LD, Ellington AD, Vandenberg CL, Georgiou G, Antibody repertoires in humanized NOD-scid-IL2Rγ(null) mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse, PLoS ONE 7(4):e35497
2011 Sürmeli G, Akay T, Ippolito GC, Tucker PW, Jessell ™, Patterns of spinal sensory-motor connectivity prescribed by a dorsoventral positional template, Cell 147(3):653-65
2011 Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, Ippolito GC, Fujiwara Y, Ebert BL, Tucker PW, Orkin SH, Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing, Science 334(6058):993-6
2010 Feng X, Ippolito GC, Tian L, Wiehagen K, Oh S, Sambandam A, Willen J, Bunte RM, Maika SD, Harriss JV, Caton AJ, Bhandoola A, Tucker PW, Hu H, Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development, Blood 115(3):510-8
2009 Sankaran VG, Xu J, Ragoczy T, Ippolito GC, Walkley CR, Maika SD, Fujiwara Y, Ito M, Groudine M, Bender MA, Tucker PW, Orkin SH, Developmental and species-divergent globin switching are driven by BCL11A, Nature 460(7259):1093-7
2009 Schmidt C, Kim D, Ippolito GC, Naqvi HR, Probst L, Mathur S, Rosas-Acosta G, Wilson VG, Oldham AL, Poenie M, Webb CF, Tucker PW, Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright, EMBO J 28(6):711-24
2008 Zemlin M, Schelonka RL, Ippolito GC, Zemlin C, Zhuang Y, Gartland GL, Nitschke L, Pelkonen J, Rajewsky K, Schroeder HW Jr, Regulation of repertoire development through genetic control of DH reading frame preference, J Immunol 181(12):8416-24
2007 Koon HB, Ippolito GC, Banham AH, Tucker PW, FOXP1: a potential therapeutic target in cancer, Expert Opin Ther Targets 11(7):955-65
2007 Lin D, Ippolito GC, Zong RT, Bryant J, Koslovsky J, Tucker P. Bright/ARID3A contributes to chromatin accessibility of the immunoglobulin heavy chain enhancer, Mol Cancer 26;6:23
2006 Ippolito GC, Schelonka RL, Zemlin M, Ivanov II, Kobayashi R, Zemlin C, Gartland GL, Nitschke L, Pelkonen J, Fujihashi K, Rajewsky K, Schroeder HW Jr, Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production, J Exp Med 203(6):1567-78
2006 Pulford K, Banham AH, Lyne L, Jones M, Ippolito GC, Liu H, Tucker PW, Roncador G, Lucas E, Ashe S, Stockwin L, Walewska R, Karran L, Gascoyne RD, Mason DY, Dyer MJ, The BCL11AXL transcription factor: its distribution in normal and malignant tissues and use as a marker for plasmacytoid dendritic cells, Leukemia. 2006 Aug;20(8):1439-41.
2006 Liu H, Ippolito GC, Wall JK, Niu T, Probst L, Lee BS, Pulford K, Banham AH, Stockwin L, Shaffer AL, Staudt LM, Das C, Dyer MJ, Tucker PW, Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells, Mol Cancer 5:18