Assistant Professor
Department of Biological Sciences
Towson University
Towson, MD 21252 USA
Office: Smith 253
Phone: 410-704-4817
Fax: 410-704-2405
email: msnyder@towson.edu
Education:
Postdoc National Institutes of Health
Ph.D. Northwestern University
B.S. Calvin College
Courses Taught:
BIOL 408/508—Cell Biology
BIOL 421/521—Immunology
BIOL 486—Biology Majors Seminar
Research Interests:
The immune system is the body's line of defense against disease-causing bacteria, viruses and fungi. In order to carry out its
function the immune system must be able to distinguish self from non-self. If the immune system fails to detect foreign invading
pathogens, the body succumbs to infection and possible death. On the other hand, if the system mounts an attack against its
own tissues, autoimmunity can develop.
It has been recently appreciated that the crucial ability of the immune system to quickly detect foreign invading pathogens is a function
of an evolutionarily ancient arm of the system, termed the innate system. Cells of the innate system have evolved to distinguish
pathogens from self by recognizing highly conserved pathogen-associated molecular patterns (PAMPs) through a similarly-conserved
array of surface-associated pattern-recognition receptors (PRRs). PRRs used by mammalian immune systems have been identified in organisms as diverse as horseshoe crabs, tomatoes, worms and fruitflies. In fact, some of the ground-breaking work in identifying
the PRRs by which innate immune systems recognize invading pathogens was completed in fruitflies.
The slime mold Dictyostelium discoideum is a unique model organism that exists for part of its lifecycle as unicellular amoebae
but is induced to form a multicellular sporulating body upon starvation. The amoeboid cells phagocytose bacteria for nutrient uptake,
and this process is utilized in higher organisms by innate immune cells to eliminate invading bacteria. Due to the ease with which
they can be cultured and genetically manipulated, Dictyostelium amoebae have long been used to study the process of phagocytosis.
It has not been appreciated, however, whether Dictyostelium detect bacteria using the same types of PRRs as do innate immune cells.
The research in our laboratory is aimed at studying Dictyostelium responses to known PAMPs found in bacteria, fungi and viruses.
Our preliminary studies have revealed that Dictyostelium amoebae can indeed respond to known PAMPs, suggesting that elements
of the pattern-recognition machinery used by innate immune systems in higher organisms are conserved. We are taking advantage
of the manipulability of the Dictyostelium genome to identify and study particular gene products that may be involved in the Dictyostelium response to PAMPs. Characterization of such proteins in Dictyostelium may allow for identification of novel players conserved in the
innate immune systems of mammals.
Although the immune system has developed to recognize and eliminate foreign organisms, various pathogens have evolved strategies to evade immune responses. Some pathogens such as Mycobacterium tuberculae have evolved strategies to evade mammalian immune surveillance by acquiring the ability to survive within phagosomes of innate immune cells. Recent studies have shown that microbial
pathogens also can infect and survive within phagosomes of Dictyostelium. We are working to develop a model system using
Dictyostelium and Mycobacterium bovis BCG (a weakened Mycobacterium strain that is safely administered as part of a vaccine for tuberculosis in much of the developing world). We hope that such a system will allow us to translate our findings related to pattern
recognition in Dictyostelium to host-pathogen interactions in human diseases such as tuberculosis.
Publications:
Snyder MD and Pierce SK. (2006) A mutation in Epstein-Barr Virus LMP2A reveals a role for phospholipase D in B-cell antigen
receptor trafficking. Traffic 7:993-1006.
Oppenheim JJ, Dong HF, Plotz P, Caspi RR, Dykstra M, Pierce S, Martin O, Carlos C, Finn O, Koul O and Howard OM. (2005)
Autoantigens act as tissue-specific chemoattractants. J Leukoc Biol 77:854-61.
Cherukuri A, Tzeng SJ, Gidwani A, Sohn HW, Tolar P, Snyder MD and Pierce SK. (2004) Isolation of lipid rafts from B lymphocytes.
Methods Mol Biol 271:213-24.
Dykstra M, Cherukuri A, Sohn HW, Tzeng SJ and Pierce SK. (2003) Location is everything: lipid rafts and immune cell signaling.
Annu Rev Immunol 21:457-81.
Stoddart A, Dykstra ML, Brown BK, Song W, Pierce SK and Brodsky FM. (2002) Lipid rafts unite signaling cascades with clathrin
to regulate BCR internalization. Immunity 17:451-62.
Merchant M, Swart R, Katzman RB, Ikeda M, Ikeda A, Longnecker R, Dykstra ML and Pierce SK. (2001) The effects of the Epstein-Barr
virus membrane protein 2A on B cell function. Int Rev Immunol 20:805-35.
Dykstra ML, Longnecker R and Pierce SK. (2001) Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport
function of the BCR. Immunity 14:57-67.
Dykstra M, Cherukuri A and Pierce SK. (2001) Rafts and synapses in the spatial organization of immune cell signaling receptors.
J Leukoc Biol 70:699-707.
Cherukuri A, Dykstra M and Pierce SK. (2001) Floating the raft hypothesis: lipid rafts play a role in immune cell activation. Immunity
14:675-60.
Dykstra ML, Cherukuri A and Pierce SK. (2001) Floating the raft hypothesis for immune receptors: access to rafts controls receptor
signaling and trafficking. Traffic 2:160-6.
Cheng PC, Cherukuri A, Dykstra M, Malapati S, Sproul T, Chen MR and Pierce SK. (2001) Floating the raft hypothesis: the roles of
lipid rafts in B cell antigen receptor function. Semin Immunol 13:107-14.
Graduate Students:
Jessica Hannah: Characterization of the Dictyostelium Toll/interleukin-1 receptor domain-containing protein TirA
Undergraduate Students:
Ben Horrigan & Uju Nnameka: Oxidative responses of Dictyostelium amoeboid cells to pathogen-associated molecular patterns.
Viet Hoang: Characterization of the Dictyostelium Toll/interleukin-1 receptor domain-containing protein TirA.