Gary Litman

Gary Litman, PHD

Endowed Chair, College of Medicine Pediatrics

Associate Vice Dean for Research, Children's Research Institute, Pediatrics/Morsani College of Medicine

Vice Chairman for Basic Sciences, Pediatrics/Morsani College of Medicine

Director, Children's Research Institute, Pediatrics/Morsani College of Medicine

Distinguished University Professor, Pediatrics/Morsani College of Medicine

Professor, Pediatrics/Morsani College of Medicine

Contact Info 140 7th Avenue South
CRI 3008
St. Petersburg FL 33701

Academic Email: glitman1@jhmi.edu

Academic Phone:(727) 553-3601

View My C.V.

Education

  • PHD, Microbiology, University of Minnesota, 1972
  • BA, Microbiology, University of Minnesota, 1967

Interdisciplinary and Emerging Signature Programs

  • Allergy, Immunology & Infectious Disease

Research Interests

  • The immune system is the most complex genetic system described to date. Using a number of different approaches, studies conducted in our laboratory have identified key aspects of the development of the lymphoid system and are shedding light on the origins of mechanisms that create immune receptor diversity as well as the nature of those features of the genome that promote genetic recombination, a major factor in both immune diversity and cancer. Over the past several years, we have defined several extensively diversified families of putative immune receptors possessing distinct structural and regulatory features. In the process, we have identified alternative mechanisms for creating immune diversity, different forms of recognition that may function in innate immunity in humans and alternative pathways of receptor diversification. Novel innate immune molecules have been identified that potentially utilize alternative signaling pathways for mediating immune function and as such have enhanced our understanding of integration of regulatory networks that factor in host protection.
  • Current efforts focus on two model systems, zebrafish and Ciona, that afford distinct experimental advantages. Zebrafish have been shown by us to possess two major novel families of immune receptor genes that encode variable region domains in addition to those that function in the mammalian-like adaptive immune system of this species. Although one of the gene families, novel immune-type receptors (NITRs), appears to encode natural killer (NK) receptors, the role of the other multigene family, diverse immunoglobulin domain-containing proteins (DICPs), presently is not understood. DICPs bind lipid ligands and lack a homolog outside of bony fish. Different transgenic approaches are being used to determine how these extraordinarily diverse genes function in innate immunity. The role of repetitive DNA in genome stability is being investigated in a zebrafish read-out model and efforts are being made to understand lipid binding as a basic mechanism in modulating innate immune function in the CD300/TREM gene families in higher vertebrate models.
  • Ciona, a marine urochordate, is being developed as a model to study general features of gut immunity and serves as a gnotobiotic system that can be used to study microbial influences on inflammatory gut pathology in the absence of influences from the adaptive immune system which is not found outside of vertebrates. We have shown that the variable region-containing chitin-binding proteins (VCBPs) in Ciona function in phagocytosis and that these molecules may represent a determining factor in shaping the microbial communities of the gut. The immune phenotype of the dysbiotic gut and the Ciona colitis model are being investigated. Gene silencing approaches (including dietary introduction of dsRNA) are being evaluated as tools to dissect the role of various innate immune receptors in gut-mediated immune dynamics.
  • Our laboratory has a longstanding interest in the molecular basis for primary immunodeficiency disease and has characterized genotype-phenotype relationships in X-linked agammaglobulinemia as well as the basis for antibody diversity in DiGeorge Syndrome. More recent efforts are focused on the role of gene conversion in the pathogenesis of selected B cell immunodeficiencies.

Memberships

  • The Henry Kunkel Society (Member, 2001 - Present)
  • American Society of Human Genetics (Member, 1990 - Present)
  • American Society for Biochemistry and Molecular Biology (Member, 1979 - Present)
  • International Society for Developmental and Comparative Immunology (Member, 1975 - Present)
  • American Association of Immunologists (Member, 1973 - Present)

Recent Publications

  • Kornfeld, SJ.Haire, RN.Litman, GW. Adult diagnosed primary immunodeficiency disease Journal of the American Medical Association. (12) : 937-942
  • Dishaw LJ Leigh B Cannon JP Liberti A Mueller MG Skapura DP Karrer CR Pinto MR De Santis R Litman GW. Gut immunity in a protochordate involves a secreted immunoglobulin-type mediator binding host chitin and bacteria. Nat Commun. 15(7) : 10617, 2016.
  • Gemayel KT, Litman GW, Sriaroon P. Autosomal recessive agammaglobulinemia associated with an IGLL1 gene missense mutation. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. , 2016. http://www.ncbi.nlm.nih.gov/pubmed/27576013
  • Zhang L, Li L, Guo X, Litman GW, Dishaw LJ, Zhang G. Massive expansion and functional divergence of innate immune genes in a protostome. Scientific Reports. 5: 8693, 2015. http://www.ncbi.nlm.nih.gov/pubmed/25732911
  • Litman GW, Dishaw LJ. Early histocompatibility: color the mechanism green and red. Current Biology : CB. 25(21) : R1042-3, 2015. http://www.ncbi.nlm.nih.gov/pubmed/26528746
  • Kortum AN, Rodriguez-Nunez I, Yang J, Shim J, Runft D, O'Driscoll ML, Haire RN, Cannon JP, Turner PM, Litman RT, Kim CH, Neely MN, Litman GW, Yoder JA. Differential expression and ligand binding indicate alternative functions for zebrafish polymeric immunoglobulin receptor (pIgR) and a family of pIgR-like (PIGRL) proteins. Immunogenetics. 66(4) : 267-79, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24469064
  • Dishaw LJ, Flores-Torres J, Lax S, Gemayel K, Leigh B, Melillo D, Mueller MG, Natale L, Zucchetti I, De Santis R, Pinto MR, Litman GW, Gilbert JA. The gut of geographically disparate Ciona intestinalis harbors a core microbiota. PloS ONE. 9(4) : e93386, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24695540
  • Liberti A, Melillo D, Zucchetti I, Natale L, Dishaw LJ, Litman GW, De Santis R, Pinto MR. Expression of Ciona intestinalis variable region-containing chitin-binding proteins during development of the gastrointestinal tract and their role in host-microbe interactions. PloS ONE. 9(5) : e94984, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24788831
  • Boudinot P Zou J Ota T Bounocore F Scapigliati G Canapa A Cannon J Litman G Hansen JD. tetrapod-like repertoire of innate immune receptors and effectors for coelacanths. J Exp Zool (Mol Dev Evol). : 1-22, 2014.
  • Saha NR, Ota T, Litman GW, Hansen J, Parra Z, Hsu E, Buonocore F, Canapa A, Cheng JF, Amemiya CT. Genome complexity in the coelacanth is reflected in its adaptive immune system. Journal of Experimental Zoology. Part B, Molecular and developmental evolution. 322(6) : 438-63, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24464682
  • Litman GW Dishaw LJ. Dispatch. Histocompatibility: clarifying fusion confusion. Curr Op Immunol. : R934-935, 2013.
  • Amemiya CT, Alföldi J, Lee AP, Fan S, Philippe H, Maccallum I, Braasch I, Manousaki T, Schneider I, Rohner N, Organ C, Chalopin D, Smith JJ, Robinson M, Dorrington RA, Gerdol M, Aken B, Biscotti MA, Barucca M, Baurain D, Berlin AM, Blatch GL, Buonocore F, Burmester T, Campbell MS, Canapa A, Cannon JP, Christoffels A, De Moro G, Edkins AL, Fan L, Fausto AM, Feiner N, Forconi M, Gamieldien J, Gnerre S, Gnirke A, Goldstone JV, Haerty W, Hahn ME, Hesse U, Hoffmann S, Johnson J, Karchner SI, Kuraku S, Lara M, Levin JZ, Litman GW, Mauceli E, Miyake T, Mueller MG, Nelson DR, Nitsche A, Olmo E, Ota T, Pallavicini A, Panji S, Picone B, Ponting CP, Prohaska SJ, Przybylski D, Saha NR, Ravi V, Ribeiro FJ, Sauka-Spengler T, Scapigliati G, Searle SM, Sharpe T, Simakov O, Stadler PF, Stegeman JJ, Sumiyama K, Tabbaa D, Tafer H, Turner-Maier J, van Heusden P, White S, Williams L, Yandell M, Brinkmann H, Volff JN, Tabin CJ, Shubin N, Schartl M, Jaffe DB, Postlethwait JH, Venkatesh B, Di Palma F, Lander ES, Meyer A, Lindblad-Toh K. The African coelacanth genome provides insights into tetrapod evolution. Nature. 496(7445) : 311-6, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23598338
  • Dishaw LJ, Litman GW. Changing views of the evolution of immunity. Frontiers in Immunology. 4: 122, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23734152
  • Dishaw LJ Haire RN Litman GW. The amphioxus genome provides unique insight into the evolution of immunity. Brief Funct Genomics. 11: 167-176, 2012.
  • Dishaw LJ, Flores-Torres JA, Mueller MG, Karrer CR, Skapura DP, Melillo D, Zucchetti I, De Santis R, Pinto MR, Litman GW. A Basal chordate model for studies of gut microbial immune interactions. Frontiers in Immunology. 3: 96, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22563328
  • Haire RN, Cannon JP, O'Driscoll ML, Ostrov DA, Mueller MG, Turner PM, Litman RT, Litman GW, Yoder JA. Genomic and functional characterization of the diverse immunoglobulin domain-containing protein (DICP) family. Genomics. 99(5) : 282-91, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22386706
  • Cannon JP, O'Driscoll M, Litman GW. Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics. 64(1) : 39-47, 2012. http://www.ncbi.nlm.nih.gov/pubmed/21800138
  • Yoder JA Litman GW. The phylogenetic origins of natural killer receptors and recognition: relationships, August 15, 2016 18 possibilities, and realities. Immunogenet. 63: 123-141, 2011.
  • Cannon JP O’Driscoll ML Litman GW. Construction, expression and purification of chimeric protein reagents based on immunoglobulin Fc regions. n Methods in Molecular Biology: Immune Receptors, Rast JP and Booth JW, eds.. 748: 51-67, 2011.
  • Dishaw LJ, Giacomelli S, Melillo D, Zucchetti I, Haire RN, Natale L, Russo NA, De Santis R, Litman GW, Pinto MR. A role for variable region-containing chitin-binding proteins (VCBPs) in host gut-bacteria interactions. Proceedings of the National Academy of Sciences of the United States of America. 108(40) : 16747-52, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21930927
  • Litman GW, Rast JP, Fugmann SD. The origins of vertebrate adaptive immunity. Nature Reviews. Immunology. 10(8) : 543-53, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20651744
  • Cannon JP Dishaw LJ Haire RN Litman RT Ostrov DA Litman GW. Recognition of additional roles for immunoglobulin domains in immune function. Sem Immunol. 22: 17-24, 2010.
  • Dishaw LJ, Ota T, Mueller MG, Cannon JP, Haire RN, Gwatney NR, Litman RT, Litman GW. The basis for haplotype complexity in VCBPs, an immune-type receptor in amphioxus. Immunogenetics. 62(9) : 623-31, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20652563
  • Litman GW, Cannon JP. Immunology: Immunity's ancient arms. Nature. 459(7248) : 784-6, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19516328
  • Dishaw LJ, Litman GW. Invertebrate allorecognition: the origins of histocompatibility. Current Biology : CB. 19(7) : R286-8, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19368870
  • Holland LZ, Albalat R, Azumi K, Benito-Gutiérrez E, Blow MJ, Bronner-Fraser M, Brunet F, Butts T, Candiani S, Dishaw LJ, Ferrier DE, Garcia-Fernàndez J, Gibson-Brown JJ, Gissi C, Godzik A, Hallböök F, Hirose D, Hosomichi K, Ikuta T, Inoko H, Kasahara M, Kasamatsu J, Kawashima T, Kimura A, Kobayashi M, Kozmik Z, Kubokawa K, Laudet V, Litman GW, McHardy AC, Meulemans D, Nonaka M, Olinski RP, Pancer Z, Pennacchio LA, Pestarino M, Rast JP, Rigoutsos I, Robinson-Rechavi M, Roch G, Saiga H, Sasakura Y, Satake M, Satou Y, Schubert M, Sherwood N, Shiina T, Takatori N, Tello J, Vopalensky P, Wada S, Xu A, Ye Y, Yoshida K, Yoshizaki F, Yu JK, Zhang Q, Zmasek CM, de Jong PJ, Osoegawa K, Putnam NH, Rokhsar DS, Satoh N, Holland PW. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome research. 18(7) : 1100-11, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18562680
  • Dishaw LJ, Mueller MG, Gwatney N, Cannon JP, Haire RN, Litman RT, Amemiya CT, Ota T, Rowen L, Glusman G, Litman GW. Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus. BMC Genetics. 9: 78, 2008. http://www.ncbi.nlm.nih.gov/pubmed/19046437
  • Cannon JP, Haire RN, Magis AT, Eason DD, Winfrey KN, Hernandez Prada JA, Bailey KM, Jakoncic J, Litman GW, Ostrov DA. A bony fish immunological receptor of the NITR multigene family mediates allogeneic recognition. Immunity. 29(2) : 228-37, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18674935
  • Litman GW, Cooper MD. Why study the evolution of immunity? Nature Immunology. 8(6) : 547-8, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17514203
  • Rast JP, Smith LC, Loza-Coll M, Hibino T, Litman GW. Genomic insights into the immune system of the sea urchin. Science. 314(5801) : 952-6, 2006. http://www.ncbi.nlm.nih.gov/pubmed/17095692
  • Litman GW. How Botryllus chooses to fuse. Immunity. 25(1) : 13-5, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16860752
  • Hernández Prada JA, Haire RN, Allaire M, Jakoncic J, Stojanoff V, Cannon JP, Litman GW, Ostrov DA. Ancient evolutionary origin of diversified variable regions demonstrated by crystal structures of an immune-type receptor in amphioxus. Nature immunology. 7(8) : 875-82, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16799561
  • Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nature reviews. Immunology. 5(11) : 866-79, 2005. http://www.ncbi.nlm.nih.gov/pubmed/16261174
  • Litman GW, Cannon JP, Rast JP. New insights into alternative mechanisms of immune receptor diversification. Advances in immunology. 87: 209-36, 2005. http://www.ncbi.nlm.nih.gov/pubmed/16102575
  • Eason DD, Cannon JP, Haire RN, Rast JP, Ostrov DA, Litman GW. Mechanisms of antigen receptor evolution. Seminars in immunology. 16(4) : 215-26, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15522620
  • Cannon JP, Haire RN, Schnitker N, Mueller MG, Litman GW. Individual protochordates have unique immune-type receptor repertoires. Current biology. 14(12) : R465-6, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15203016
  • Yoder JA, Litman RT, Mueller MG, Desai S, Dobrinski KP, Montgomery JS, Buzzeo MP, Ota T, Amemiya CT, Trede NS, Wei S, Djeu JY, Humphray S, Jekosch K, Hernandez Prada JA, Ostrov DA, Litman GW. Resolution of the novel immune-type receptor gene cluster in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 101(44) : 15706-11, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15496470
  • Ota T, Rast JP, Litman GW, Amemiya CT. Lineage-restricted retention of a primitive immunoglobulin heavy chain isotype within the Dipnoi reveals an evolutionary paradox. Proceedings of the National Academy of Sciences of the United States of America. 100(5) : 2501-6, 2003. http://www.ncbi.nlm.nih.gov/pubmed/12606718
  • Cannon JP, Haire RN, Litman GW. Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate. Nature immunology. 3(12) : 1200-7, 2002. http://www.ncbi.nlm.nih.gov/pubmed/12415263
  • Yoder JA, Hawke NA, Eason DD, Mueller MG, Davids BJ, Gillin FD, Litman GW. BIVM, a novel gene widely distributed among deuterostomes, shares a core sequence with an unusual gene in Giardia lamblia. Genomics. 79(6) : 750-5, 2002. http://www.ncbi.nlm.nih.gov/pubmed/12036287
  • Yoder JA, Mueller MG, Wei S, Corliss BC, Prather DM, Willis T, Litman RT, Djeu JY, Litman GW. Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster. Proceedings of the National Academy of Sciences of the United States of America. 98(12) : 6771-6, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11381126
  • Miracle AL, Anderson MK, Litman RT, Walsh CJ, Luer CA, Rothenberg EV, Litman GW. Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire. International immunology. 13(4) : 567-80, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11282996
  • Hawke NA, Yoder JA, Haire RN, Mueller MG, Litman RT, Miracle AL, Stuge T, Shen L, Miller N, Litman GW. Extraordinary variation in a diversified family of immune-type receptor genes. Proceedings of the National Academy of Sciences of the United States of America. 98(24) : 13832-7, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11698645
  • Litman GW, Hawke NA, Yoder JA. Novel immune-type receptor genes. Immunological reviews. 181: 250-9, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11513146
  • Yoder JA, Litman GW. Immune-type diversity in the absence of somatic rearrangement. Current topics in microbiology and immunology. 248: 271-82, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10793482
  • Strong SJ, Mueller MG, Litman RT, Hawke NA, Haire RN, Miracle AL, Rast JP, Amemiya CT, Litman GW. A novel multigene family encodes diversified variable regions. Proceedings of the National Academy of Sciences of the United States of America. 96(26) : 15080-5, 1999. http://www.ncbi.nlm.nih.gov/pubmed/10611341
  • Litman GW, Anderson MK, Rast JP. Evolution of antigen binding receptors. Annual review of immunology. 17: 109-47, 1999. http://www.ncbi.nlm.nih.gov/pubmed/10358755
  • Bykowsky MJ, Haire RN, Ohta Y, Tang H, Sung SS, Veksler ES, Greene JM, Fu SM, Litman GW, Sullivan KE. Discordant phenotype in siblings with X-linked agammaglobulinemia. American journal of human genetics. 58(3) : 477-83, 1996. http://www.ncbi.nlm.nih.gov/pubmed/8644706
  • de la Morena M, Haire RN, Ohta Y, Nelson RP, Litman RT, Day NK, Good RA, Litman GW. Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia. European journal of immunology. 25(3) : 809-15, 1995. http://www.ncbi.nlm.nih.gov/pubmed/7705412
  • Ohta Y, Haire RN, Litman RT, Fu SM, Nelson RP, Kratz J, Kornfeld SJ, de la Morena M, Good RA, Litman GW. Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia. Proceedings of the National Academy of Sciences of the United States of America. 91(19) : 9062-6, 1994. http://www.ncbi.nlm.nih.gov/pubmed/8090769
  • Haire RN, Buell RD, Litman RT, Ohta Y, Fu SM, Honjo T, Matsuda F, de la Morena M, Carro J, Good RA. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome. The Journal of experimental medicine. 178(3) : 825-34, 1993. http://www.ncbi.nlm.nih.gov/pubmed/8350056

Positions Held

  • Senior Member/Chairman (Molecular Genetics, Tampa Bay Research Institute 1985 - 1990)
  • Associate Professor (Immunology/Sloan-Kettering Division, Cornell University 1980 - 1985)
  • Chairman (Biology Unit/Sloan-Kettering Division, Cornell University 1978 - 1985)
  • Associate Professor (Genetics/Sloan-Kettering Division, Cornell University 1976 - 1985)
  • Director (Special Clinical Immunochemistry Laboratory, Memorial Sloan-Kettering Cancer Center 1975 - 1985)
  • Associate Member/Head (Macromolecular Biochemistry Section, Sloan-Kettering Institute 1972 - 1985)
  • Associate Professor (Biology/Sloan-Kettering Division, Cornell University 1973 - 1980)
  • Assistant Professor (Pathology, University of Minnesota 1972 - 1972)
  • Director (Clinical Laboratory of Immunochemistry/Pathology, University of Minnesota 1971 - 1972)
  • Instructor (Pediatrics and Pathology, University of Minnesota 1970 - 1972)
  • Director (Clinical Laaboratory of Immunochemistry/Pediatrics, University of Minnesota 1969 - 1971)
  • Teaching Specialist (Pediatrics, University of Minnesota 1968 - 1970)
  • Research Assistant (Microbiology, University of Minnesota 1967 - 1968)

Awards/Honors

  • Distinguished University Professor (University of South Florida - 2004)
  • Outstanding Faculty Research Achievement Award (University of South Florida - 2002)
  • Induction (The Henry Kunkel Society - 2001)
  • MERIT Award (NIH - 1995)