Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Microbiology and Immunology
Additional Title:
Professor
Location:
Bressler Research Building, 3-056
Phone (Primary):
(410) 706-5161
Fax:
(410) 706-2129
Education and Training
Pennsylvania State University B.S. 1978
University of Rochester, NY M.S. 1979
University of Rochester, NY Ph.D. 1983
Basel Institute for Immunology, CH Member (actually Postdoc) 1983-1988
University of Miami School of Medicine Assistant Professor 1988-1992
Department of Microbiology & Immunology
University of Miami School of Medicine Associate Professor 1992-1996
Department of Microbiology & Immunology (promoted with tenure)
University of Miami School of Medicine Professor 1996-1998
Department of Microbiology & Immunology
University of Maryland at Baltimore Professor 1998-present
Department of Microbiology & Immunology
Research/Clinical Keywords
Origins of adaptive immunity; major histocompatibility complex; single-domain antibodies; emergence of T cell receptors and immunoglobulins; evolution of lymphoid tissues
Highlighted Publications
Flajnik MF, Stanfield RL, Verissimo A, Neely HR, Muñoz-Mérida A, Criscitiello MF, Wilson IA, Ohta Y. 2025. Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon. Science Advances 11(27):eadw1273.
Quiniou SMA, Clark T, Bengtén E, Rast JP, Ohta Y, Flajnik MF, Boudinot P. 2024 Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates. Front Immunol. 15:1501934.
Flajnik MF. 2024.The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms. Immunol Rev. 328(1):49-64.
Kawasaki K, Ohta Y, Castro CD, Flajnik MF. 2024. The immunoglobulin J chain is an evolutionarily co-opted chemokine. Proc Natl Acad Sci U S A. 121(3):e2318995121.
Veríssimo A, Castro LFC, Muñoz-Mérida A, Almeida T, Gaigher A, Neves F, Flajnik MF, Ohta Y. 2023. An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution. Mol Biol Evol. 1;40(12):msad262.
Janes ME, Kinlein A, Flajnik MF, Du Pasquier L, Ohta Y. 2023. Genomic view of the origins of cell-mediated immunity. Immunogenetics 75(6):479-493
Flajnik MF, Stanfield R, Pokidysheva EN, Boudko SP, Wilson I, Ohta Y. 2023. An Ancient MHC- Linked Gene Encodes a Nonrearranging Shark Antibody, UrIg, Convergent with IgG. J Immunol. 15;211(6):1042-1051.
Flajnik, M.F. 2022. Evolution of the immune system. In: “Fundamental Immunology, 7th edition,” WE Paul, editor. Lippincroft-Raven, Philadelphia.
Flowers EM, Neely HR, Guo J, Almeida T, Ohta Y, Castro CD, Flajnik MF. 2021. Identification of the Fc-alpha/mu receptor in Xenopus provides insight into the emergence of the poly-Ig receptor (pIgR) and mucosal Ig transport. Eur J Immunol. 51(11):2590-2606.
Almeida T, Ohta Y, Gaigher A, Muñoz-Mérida A, Neves F, Castro LFC, Machado AM, Esteves PJ, Veríssimo A, Flajnik MF.A Highly Complex, MHC-Linked, 350 Million-Year-Old Shark Nonclassical Class I Lineage. J Immunol. 2021, 207(3):824-836.
Kinlein A, Janes ME, Kincer J, Almeida T, Matz H, Sui J, Criscitiello MF, Flajnik MF, Ohta Y. 2021. Analysis of shark NCR3 family genes reveals primordial features of vertebrate NKp30. Immunogenetics. 73(4):333-348.
Ott, J.A., Ohta, Y., Flajnik, M.F. and Criscitiello, M.F. 2021. Lost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharks. Immunogenetics. 73(1):17-33. PMID: 33449123
Almeida T, Gaigher A, Muñoz-Mérida A, Neves F, Castro LFC, Flajnik MF, Ohta Y, Esteves PJ, Veríssimo A. 2020. Cartilaginous fish class II genes reveal unprecedented old allelic lineages and confirm the late evolutionary emergence of DM. Mol Immunol. 128: 125-138. PMID: 33126081
Almeida T, Esteves PJ, Flajnik MF, Ohta Y, Veríssimo A. 2020 An Ancient, MHC-Linked, Nonclassical Class I Lineage in Cartilaginous Fish. J Immunol. 204(4):892-902. PMID:31932500
Ohta, Y., Kasahara, M., O’Connor, T.D. and Flajnik, M.F., 2019. Inferring the “Primordial Immune Complex”: origins of MHC class I and antigen receptors revealed by comparative genomics. The Journal of Immunology, 203(7): 1882-1896. PMID: 31492741
Ohta Y, Kasahara M, O’Connor, and Flajnik MF. 2019 Emergence of the MHC and CD1 and genome-wide duplications early in vertebrate history. J. Immunol.203:1882-1896.
Kasahara M, and Flajnik MF. 2019 Origin and evolution of the specialized forms of proteasomes involved in antigen presentation. Immunogenetics 71:251-261.
Yaari G, Flajnik MF, and Hershberg U. 2018. Questions of Stochasticity and Control in Immune Repertoires. Trends Immunol. 39:859-861.
Ott JA, Castro CD, Deiss TC, Ohta Y, Flajnik MF, and Criscitiello MF. 2018. Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus. Elife 17;7. pii: e28477.
Neely HR, Guo J, Criscitiello MF, and Flajnik MF. 2018. A single lineage of “double duty” dendritic cell properties in the amphibian Xenopus. Eur J Immunol 48:430-440.
Flajnik MF. A cold-blooded view of vertebrate adaptive immunity. Nature Rev. Immunol. 18:438-453.
Iacoangeli A, Lui A, Haines A, Ohta Y, Flajnik MF, Hsu E. 2017. Mechanisms enforcing immunoglobulin light chain isotype exclusion in shark B lymphocytes. J. Immunol. 199(5):1875-1885
Session AM, Uno Y, Kwon T, Chapman JA, Toyoda A, Takahashi S, Fukui A, Hikosaka A, Suzuki A, Kondo M, van Heeringen SJ, Quigley I, Heinz S, Ogino H, Ochi H, Hellsten U, Lyons JB, Simakov O, Putnam N, Stites J, Kuroki Y, Tanaka T, Michiue T, Watanabe M, Bogdanovic O, Lister R, Georgiou G, Paranjpe SS, van Kruijsbergen I, Shu S, Carlson J, Kinoshita T, Ohta Y, Mawaribuchi S, Jenkins J, Grimwood J, Schmutz J, Mitros T, Mozaffari SV, Suzuki Y, Haramoto Y, Yamamoto TS, Takagi C, Heald R, Miller K, Haudenschild C, Kitzman J, Nakayama T, Izutsu Y, Robert J, Fortriede J, Burns K, Lotay V, Karimi K, Yasuoka Y, Dichmann DS, Flajnik MF, Houston DW, Shendure J, DuPasquier L, Vize PD, Zorn AM, Ito M, Marcotte EM, Wallingford JB, Ito Y, Asashima M, Ueno N, Matsuda Y, Veenstra GJ, Fujiyama A, Harland RM, Taira M, Rokhsar DS. 2016 Nature 538:336-3
Flajnik M.F. 2016. Evidence of GOD's Miracle: Unearthing a RAG Transposon. Cell 166:11-12.
Neely H. and Flajnik M.F. 2015. CXCL13 responsiveness but not CXCR5 expression by late transitional B cells initiates splenic white pulp formation. J. Immunol. 194:2613-2623.
Ohta Y., Flajnik M.F. 2015. Coevolution of MHC genes (LMP/TAP/class Ia, NKT-class Ib, NKp30-B7H6): lessons from cold-blooded vertebrates. Immunol Rev. 267:6-15.
Flajnik, M.F. 2014.Two “Big Bangs” may explain the evolution of the adaptive immune system: 1) Emergence of a primordial transcriptional network in lymphocytes and 2) Expansion of effector functions. Current Biol. 24(21):R1060-5
Castro CD and Flajnik M.F. 2014. Putting J-chain back on the map: how might its expression define plasma cell development?" J. Immunology 193:3248-3255.
Venkatesh B, Lee AP, Ravi V, Maurya AK, Lian MM, Swann JB, Ohta Y, Flajnik M.F., Sutoh Y, Kasahara M, Hoon S, Gangu V, Roy SW, Irimia M, Korzh V, Kondrychyn I, Lim ZW, Tay BH, Tohari S, Kong KW, Ho S, Lorente-Galdos B, Quilez J, Marques-Bonet T, Raney BJ, Ingham PW, Tay A, Hillier LW, Minx P, Boehm T, Wilson RK, Brenner S, Warren WC. 2014. Elephant shark genome provides unique insights into gnathostome evolution. Nature 505:174-9. PMID: 24402279
Flajnik, M.F., Deschacht, N., and Muyldermans, S. 2011. A case of convergence: why did a simple alternative to canonical antibodies arise in sharks and camels? PLoS Biol. 9:e1001120 (peer-reviewed).
Flajnik, M.F. 2011. Immunology. The origin of sweetbreads in lampreys? Current Biol. 21:R218-220.
Sutoh, Y., Kondo, M., Ohta, Y., Tomaru, U., Flajnik, M.F., and Kasahara, M. 2011. Comparative analysis of the proteasome beta5t subunit gene: implications for the origin and evolution of thymoproteasomes. Immunogenetics 64:49-58.
Ohta, Y., Shiina, T., Lohr, R.L., Hosomichi, K., Pollin, T.I., Heist, E.J., Suzuki, S., Inoko, H., and Flajnik, M.F. 2011. Primordial linkage of beta2-microglobulin in the MHC. J. Immunol. 186:3563-3571.
Deng, L., Velikovsky, C.A., Xu, G., Iyer, L.M., Tasumi, S., Kerzic, M.C., Flajnik, M.F., Aravind, L., Pancer, Z., and Mariuzza, R.A. 2010. A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey. Proc. Natl. Acad. Sci. 107:13408-13413.
Flajnik, M.F. 2010. All GOD’s creatures got dedicated mucosal immunity. Nature Immunol. 11:777-779.
Flajnik, M.F. and Kasahara, M. 2010. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nature Rev. Genetics 11:47-59 (peer-reviewed).
Saltis, M., Criscitiello, M.F., Ohta, Y., Keefe, M., Trede, N.S., Goitsuka, R., and Flajnik, M.F. 2008. Evolutionarily conserved and divergent regions of the autoimmune regulator (Aire) gene: a comparative analysis. Immunogenetics 60:105-114.
Criscitiello, M.F. and Flajnik, M.F. 2007. Four primordial immunoglobulin light chain isotypes, including lambda and kappa, identified in the most primitive living vertebrates. Eur. J. Immunol. 37:2683-2694.
Criscitiello, M.F., Saltis, M., Flajnik, M.F. 2006. An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks. Proc. Natl. Acad. Sci. 103:5036-5041.
Ohta, Y., Goetz, W., Hossain M.Z., Nonaka, M., and Flajnik, M.F. 2006. Ancestral organization of the MHC revealed in the amphibian Xenopus. J. Immunol. 176:3674-3685.
Ohta, Y. and Flajnik, M.F. 2006. IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates. Proc. Natl. Acad. Sci. 103:10723-10728.
Dooley, H., Stanfield, R.L., Brady, R.A., and Flajnik, M.F. 2006. First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate. Proc. Natl. Acad. Sci. 103:1846-1851.
Dooley, H. and Flajnik, M.F. 2005. Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum. Eur. J. Immunol. 35:936-945.
Flajnik, M.F. 2005. The last flag unfurled? A new immunoglobulin isotype in fish expressed early in development. Nature Immunol. 6:229-230.
Stanfield, R.L., Dooley, H., Flajnik, M.F., and Wilson, I.A. 2004. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science 305: 1769-1776.
Flajnik, M.F. and Du Pasquier, L. 2004. Evolution of innate and adaptive immunity: can we draw a line? Trends Immunol. 25:64-644.
Ohta Y., Powis S.J., Lohr, R.L., Nonaka, M., Du Pasquier, L., and Flajnik, M.F. 2003. Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among class I region genes. Eur. J. Immunol. 33:3017-3027.
Flajnik, M.F. Immunology: Another manifestation of God. 2004. Nature 430:157-158.
Hohman, V.S., Stewart, S.E., Rumfelt, L.L., Greenberg, A.S., Avila, D.W., Flajnik, M.F., and Steiner, L.A. 2003. J chain in the nurse shark: implications for function in a lower vertebrate. J. Immunol. 170:6016-6023
Rumfelt, L.L., McKinney, E.C., Taylor, E., and Flajnik, M.F. 2002. The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cells immigration and T-cell zone formation during ontogeny of the spleen. Scand. J. Immunol. 56:130-148.
Flajnik, M.F. 2002. Comparative analyses of immunoglobulin genes: surprises and portents. Nature Rev. Immunol. 2:688-698.
Flajnik, M.F. and Kasahara, M. 2001. Comparative genomics of the MHC: Glimpses into the evolution of the adaptive immune system. Immunity, 15:351-362.
Diaz, M., Verkoczy, L.K., Flajnik, M.F., and Klinman, N. 2001. A role for the translesion synthesis DNA polymerase zeta in somatic hypermutation. J. Immunol., 167:327-335.
Rumfelt, L.L., Avila, D., Diaz, M., McKinney, E.C., and Flajnik, M.F. 2001. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG. Proc. Natl. Acad. Sci. 98:1775-1780.
Ohta, Y., Okamura, K., McKinney, E.C., Bartl, S., Hashimoto, K., and Flajnik, M.F. 2000. Primitive synteny of vertebrate major histocompatibility complex class I and class II genes. Proc. Natl. Acad. Sci. 97:4712-4717.
Diaz, M., Greenberg, A.S., and Flajnik, M.F. 1998. Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: Possible role in antigen- driven reactions in the absence of germinal centers. Proc. Natl. Acad. Sci. 95:14343-14348.
Roux, K.H., Greenberg, A.S., Greene, L., Strelets, L., Avila, D., McKinney, E.C., and Flajnik, M.F. 1998. Structural analysis of the nurse shark (new) antigen receptor (NAR): Molecular convergence of NAR and unusual mammalian immunoglobulins. Proc. Natl. Acad. Sci. 95:11804-11809.
Diaz M. and Flajnik, M.F. 1998. Evolution of somatic hypermutation and gene conversion in adaptive immunity. Immunol. Rev. 162:13-24.
Nonaka, M., Namikawa, C., Kato, Y., Sasaki, M., Salter-Cid, L., and Flajnik, M.F. 1997. Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization. Proc. Natl. Acad. Sci. USA 94:5789-5791.
Greenberg, A.S., Hughes, A.L., Guo, J., Avila, D., McKinney, E.C. and Flajnik, M.F. 1996. A novel "chimeric" antibody class in cartilaginous fish: IgM may not be the primordial immunoglobulin. Eur. J. Immunol. 26:1123-1129.
Greenberg, A.S., Avila, D., Hughes, M., Hughes, A., McKinney, E.C., and Flajnik, M.F. 1995. A novel rearranging gene that undergoes extensive somatic diversification in sharks. Nature 374:168-173.
Flajnik, M.F., Kasahara, M., Shum, B.P., Salter-Cid, L., Taylor, E., and Du Pasquier, L. 1993. A novel type of class I gene organization in vertebrates: A large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus. EMBO J. 12:4385-4396.
Greenberg, A., Steiner, L., Kasahara, M., and Flajnik, M.F. 1993. Isolation of a shark immunoglobulin light chain cDNA clone encoding a protein resembling kappa light chain: Implications for the evolution of light chains. Proc. Natl. Acad. Sci. 90:10603-10607.
Kasahara, M., Vasquez, M., Sato, K., McKinney, C., and Flajnik, M. 1992. Evolution of the major histocompatibility complex: Isolation of class IIA cDNA clones from the cartilaginous fish. Proc. Natl. Acad. Sci. 89: 6688-6692.
Flajnik, M.F., Canel, C., Kramer, J., and Kasahara, M. 1991. Which came first, MHC class I or class II? Immunogenetics 33: 295-300.
Flajnik, M.F., Canel, C., Kramer, J., and Kasahara, M. 1991. Evolution of the MHC: Molecular cloning of MHC class I from the amphibian Xenopus. Proc. Natl. Acad. Sci. 88: 537- 541.
Flajnik, M.F., Kaufman, J.F., Hsu, E., Manes, M., Parisot, R., and Du Pasquier, L. 1986. Major histocompatibility complex encoded class I molecules are absent in immunologically competent Xenopus before metamorphosis. J. Immunol. 137: 3891-3899.
Hsu, E., Flajnik, M.F., and Du Pasquier, L. 1985. Identification of a third immunoglobulin class in Amphibians. J. Immunol. 135: 1998-2004.
Flajnik, M.F., Du Pasquier, L., and Cohen, N. 1985. Immune responses of thymus/lymphocyte embryonic chimeras. Studies on tolerance and MHC restriction in Xenopus. Eur. J. Immunol. 15: 540-547.
Flajnik, M.F., Kaufman, J.F., Riegert, P., and Du Pasquier, L. 1984. Identification of class I major histocompatibility complex encoded molecules in the Amphibian Xenopus. Immunogenetics 20: 134-143.
Research Interests
My work is centered on the evolution of the immune system, with the major goal being to understand the origins of adaptive immunity. The laboratory employs a "holistic" approach, using all existing methods to investigate this problem. The adaptive immune system is defined by antigen receptors of great diversity--immunoglobulin (Ig) and T cell receptors (TCR)--and by molecules encoded in the major histocompatibility complex (MHC) that present foreign antigens for T cell recognition. In addition, the adaptive immune system is contrasted to the non-adaptive or innate immune system by displaying: i) great diversity of the antigen-receptor repertoire; ii) specific and augmented memory responses; and iii) epigenetically determined self tolerance. We believe that evolutionary studies permit a judgment of those structures and mechanisms vital for a functioning immune system and reveal other phenomena that have arisen to fulfill specific functions in particular taxonomic lineages. The adaptive immune system so far has been identified only in jawed vertebrates, including the cartilaginous fish (e.g. sharks and skates), bony fish (e.g. trout, zebrafish), amphibians (e.g. Xenopus), reptiles, birds, and mammals. Our work (and that of other labs) has shown that the oldest group, the cartilaginous fish, while exhibiting an unusual immune system in which specific antibody responses do not increase in quality over time, nevertheless possess all of the building blocks of an adaptive immune system. Our goal i to piece together the building blocks of primordial adaptive immunity.
Awards and Affiliations
Major Lecture at the 7th International Congress of Immunology, Berlin (August 1989).
Major Lecture at the 9th International Congress of Immunology, San Francisco (August 1995).
"Faculty Member of the Year Award," teaching award sponsored by the Microbiology and Immunology University of Miami undergraduates, 1995
Plenary speaker: American Association of Immunologists National Meeting,1998.
“Wall of Fame” Award for UMB Medical School Teaching, UMB, 1999.
Keynote speaker: The American College of Veterinary Pathologists, Orlando, FL, 2004.
Keynote Lecture: Symposium on the history of immunology, Erlangen DE, 2007.
Teaching commendations for UMB Medical School HDID, 2000-2009.
Endowed (graduate student) speaker, University of Montana (Bozeman, April 2006).
Member of advisory/site visit committee for COBRE grant at the University of New Mexico (I traveled there once/year on a site visit, 2006-2020).
GPILS teacher of the year, UMB Graduate School (September 2008).
Plenary speaker: Florida International University, 2009.
Keynote Speaker: Johns Hopkins Immunology Retreat, September 2009.
"Immunological Guru” and plenary speaker at the NIH Immunology Retreat (September 2010).
Plenary speaker: University of Waterloo (Canada) Symposium in Comparative Immunology, 2010.
Plenary speaker, Avian Immunology Research Group, Munich, DE, 2016
Invited to participate in a week-long ‘think tank’ on antigen receptor repertoire generation at the Hebrew University in Jerusalem: “Stochasticity and Control of Immune Repertoires.” This was followed by a 5-day meeting in which I presented a talk (June 2017).
Standing member on the NIAID Immunobiology Study section, 2017-2022.
Organizer of meeting on Evolution of Immunity, Dresden Germany, July 2022.
Editor of Fundamental Immunology, 8th edition, 2022.
Grants and Contracts
1R01AI170844-01 (Flajnik) 6/14/2022-5/31/2027 4.0 calendar
NIH/NIAID $586,579 (direct)
Determining the Origins of Nonclassical Class I Molecules through Molecular and Functional Approaches
co-PI with Erin J. Adams, University of Chicago