Magdalene Yh So
- Director, Microbial Pathogenesis Program
- Professor, Immunobiology
- Professor, BIO5 Institute
- Professor, Biochemistry/Molecular Biophysics
- Professor, Animal and Comparative Biomedical Sciences
- Professor, Genetics - GIDP
- Professor, Molecular and Cellular Biology
My goals are to contribute to the research, teaching and service endeavors at the department and college level. My research goal is to understand the molecular mechanisms regulating bacterial interactions with the host, focusing in particular on pathogenic and commensal species of Neisseria. My role in teaching is to mentor postdoctoral fellows, graduate students and undergraduates with the aim of helping them to develop productive careers in science; to serve on mentoring and thesis committees of graduate students in my lab and in other labs; and to impart my knowledge to graduate students by teaching formal graduate level courses. Regarding service to the UA community, I serve on departmental and college committees, either as a member or as chair of these committees.
- Ph.D. Microbiology
- University of Washington, Seattle, Washington, United States
- Heat Stable and Heat Labile Toxins of enteropathogenic E. coli.
- Professor, University of Arizona, Tucson, Arizona (2007 - Ongoing)
- Director, Microbial Pathogenesis Program, University of Arizona, Tucson, Arizona (2007 - Ongoing)
- Professor and Chair, Department of Molecular Microbiology and Immunology, Oregon Health Sciences University (1991 - 2007)
- Member, Scripps Research Institute (1983 - 1991)
- Senior Staff, Cold Spring Harbor Labs (1980 - 1991)
No activities entered.
Directed RsrchMCB 492 (Fall 2016)
DissertationIMB 920 (Fall 2016)
Honors Independent StudyMCB 399H (Fall 2016)
Honors ThesisMIC 498H (Fall 2016)
ResearchIMB 900 (Fall 2016)
Directed RsrchMCB 392 (Spring 2016)
DissertationIMB 920 (Spring 2016)
Honors Independent StudyBIOC 299H (Spring 2016)
Prins+Molec MechanismsIMB 565 (Spring 2016)
ResearchIMB 900 (Spring 2016)
Senior CapstoneBIOC 498 (Spring 2016)
DissertationIMB 920 (Fall 2015)
Introduction to ResearchMCB 795A (Fall 2015)
ResearchIMB 900 (Fall 2015)
Senior CapstoneBIOC 498 (Fall 2015)
DissertationIMB 920 (Spring 2015)
Prins+Molec MechanismsIMB 565 (Spring 2015)
ResearchIMB 900 (Spring 2015)
DissertationIMB 920 (Fall 2014)
Introduction to ResearchMCB 795A (Fall 2014)
ResearchIMB 900 (Fall 2014)
Honors ThesisMCB 498H (Spring 2014)
Prins+Molec MechanismsIMB 565 (Spring 2014)
ResearchIMB 900 (Spring 2014)
Honors ThesisMCB 498H (Fall 2013)
Introduction to ResearchMCB 795A (Fall 2013)
ResearchIMB 900 (Fall 2013)
- Biais, N., Higashi, D. L., So, M. Y., & Ladoux, B. (2012). Techniques to Measure Pilus Retraction Forces. In Methods in Molecular Biology(pp 197-216). Springer Science and Business Media LLC2012. doi:10.1007/978-1-61779-346-2_13
- Hockenberry, A. M., Hutchens, D. M., Agellon, A., & So, M. Y. (2016). Attenuation of the Type IV pilus retraction motor influences Neisseria gonorrhoeae social and infection behavior. mBio.
- Weyand, N. J., Mancheong, M., Rendon, M. A., Maiden, M. C., & So, M. Y. (2016). Isolation and characterization of a new species of Neisseria, Neisseria musculi, from the wild house mouse. International Journal of Systematic and Environmental Microbiology.
- Rendón, M. A., Hockenberry, A. M., McManus, S. A., & So, M. Y. (2013). Sigma factor RpoN (σ(54) ) regulates pilE transcription in commensal Neisseria elongata. Molecular microbiology, 90(1).More infoHuman-adapted Neisseria includes two pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, and at least 13 species of commensals that colonize many of the same niches as the pathogens. The Type IV pilus plays an important role in the biology of pathogenic Neisseria. In these species, Sigma factor RpoD (σ(70) ), Integration Host Factor, and repressors RegF and CrgA regulate transcription of pilE, the gene encoding the pilus structural subunit. The Type IV pilus is also a strictly conserved trait in commensal Neisseria. We present evidence that a different mechanism regulates pilE transcription in commensals. Using Neisseria elongata as a model, we show that Sigma factor RpoN (σ(54) ), Integration Host Factor, and an activator we name Npa regulate pilE transcription. Taken in context with previous reports, our findings indicate pilE regulation switched from an RpoN- to an RpoD-dependent mechanism as pathogenic Neisseria diverged from commensals during evolution. Our findings have implications for the timing of Tfp expression and Tfp-mediated host cell interactions in these two groups of bacteria.
- So, M., So, M. Y., Calton, C. M., & Wade, L. K. (2013). Upregulation of ATF3 inhibits expression of the pro-inflammatory cytokine IL-6 during Neisseria gonorrhoeae infection. Cellular microbiology, 15(11).More infoNeisseria gonorrhoeae regulates the expression of epithelial cell genes, activates cytoprotective pathways in the infected cell and protects it from apoptosis. Many of these responses are enhanced by the Type IV pilus (Tfp). We tested the hypothesis that N. gonorrhoeae modulates the innate immune response by inducing expression of ATF3, a transcription factor that negatively regulates the expression of many cytokine genes. We further determined whether Tfp are involved in these events. We found that N. gonorrhoeae induces ATF3 expression in mucosal epithelial cells through activation of mitogen-activated protein kinases. Maximal ATF3 expression requires Tfp retraction. Knocking down endogenous levels of ATF3 results in higher levels of IL-6 transcript. Our findings strongly suggest that ATF3 is involved in suppressing cytokine expression during gonococcal infection. We propose a model for the role of ATF3 in the context of N. gonorrhoeae infection.
- Weyand, N. J., Wertheimer, A. M., Hobbs, T. R., Sisko, J. L., Taku, N. A., Gregston, L. D., Clary, S., Higashi, D. L., Biais, N., Brown, L. M., Planer, S. L., Legasse, A. W., Axthelm, M. K., Wong, S. W., & So, M. Y. (2013). Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer. PNAS, 110(8).More infoThe strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe-host interactions. We developed a rhesus macaque model for studying Neisseria-host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates.
- Choilean, S. N., Weyand, N. J., Neumann, C., Thomas, J., & So, M. Y. (2011). The dynamic processing of CD46 intracellular domains provides a molecular rheostat for T cell activation.. PLoS One, 16:e16287.
- Higashi, D. L., Biais, N., Weyand, N. J., Agellon, A., Sisko, J. L., Brown, L. M., & So, M. Y. (2011). N. elongata produces type IV pili that mediate interspecies gene transfer with N. gonorrhoeae. PloS One, 6(6).More infoThe genus Neisseria contains at least eight commensal and two pathogenic species. According to the Neisseria phylogenetic tree, commensals are basal to the pathogens. N. elongata, which is at the opposite end of the tree from N. gonorrhoeae, has been observed to be fimbriated, and these fimbriae are correlated with genetic competence in this organism. We tested the hypothesis that the fimbriae of N. elongata are Type IV pili (Tfp), and that Tfp functions in genetic competence. We provide evidence that the N. elongata fimbriae are indeed Tfp. Tfp, as well as the DNA Uptake Sequence (DUS), greatly enhance N. elongata DNA transformation. Tfp allows N. elongata to make intimate contact with N. gonorrhoeae and to mediate the transfer of antibiotic resistance markers between these two species. We conclude that Tfp functional for genetic competence is a trait of a commensal member of the Neisseria genus. Our findings provide a mechanism for the horizontal gene transfer that has been observed among Neisseria species.
- So, M. Y. (2011). The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation. PLoS One, 6, e16287.
- Biais, N., Higashi, D. L., Brujic, J., So, M. Y., & Sheetz, M. P. (2010). Force dependent polymorphism in Type IV pili reveals hidden epitopes.. PNAS, 107, 11358-11363.
- So, M., So, M. Y., Marri, P. R., Paniscus, M., Weyand, N. J., Rendón, M. A., Calton, C. M., Hernández, D. R., Higashi, D. L., Sodergren, E., Weinstock, G. M., & Rounsley, S. D. (2010). Genome sequencing reveals widespread virulence gene exchange among human Neisseria species. PloS One, 5(7).More infoCommensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange.
- Weyand, N. J., Calton, C. M., Higashi, D. L., Kanack, K. J., & So, M. Y. (2010). Presenilin/gamma-secretase cleaves CD46 in response to Neisseria infection. Journal of immunology (Baltimore, Md. : 1950), 184(2).More infoCD46 is a type I transmembrane protein with complement and T cell regulatory functions in human cells. CD46 has signaling and receptor properties in immune and nonimmune cells, many of which are dependent on the expression of cytoplasmic tail (cyt) isoforms cyt1 or cyt2. Little is known about how cyt1 and cyt2 mediate cellular responses. We show that CD46-cyt1 and CD46-cyt2 are substrates for presenilin/gamma-secretase (PS/gammaS), an endogenous protease complex that regulates many important signaling proteins through proteolytic processing. PS/gammaS processing of CD46 releases immunoprecipitable cyt1 and cyt2 tail peptides into the cell, is blocked by chemical inhibitors, and is prevented in dominant negative presenilin mutant cell lines. Two human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, stimulate PS/gammaS processing of CD46-cyt1 and CD46-cyt2. This stimulation requires type IV pili and PilT, the type IV pilus retraction motor, implying that mechanotransduction plays a role in this event. We present a model for PS/gammaS processing of CD46 that provides a mechanism by which signals are transduced via the cyt1 and cyt2 tails to regulate CD46-dependent cellular responses. Our findings have broad implications for understanding the full range of CD46 functions in infection and noninfection situations.
- Dietrich, M., Mollenkopf, H., So, M. Y., & Friedrich, A. (2009). Pilin regulation in the pilT mutant of Neisseria gonorrhoeae strain MS11.. FEBS Journal, 296, 248–256.
- Higashi, D. D., Zhang, G. H., Biais, N., Myers, L. R., Weyand, N. J., Elliott, D. A., & So, M. Y. (2009). Influence of Type IV pilus retraction on the architecture of the N. gonorrhoeae-infected cell cortex.. Microbiology, 155, 4084-4092.
- Higashi, D. L., Zhang, G. H., Biais, N., Myers, L. R., Weyand, N. J., Elliott, D. A., & So, M. Y. (2009). Influence of type IV pilus retraction on the architecture of the Neisseria gonorrhoeae-infected cell cortex. Microbiology (Reading, England), 155.More infoEarly in infection, Neisseria gonorrhoeae can be observed to attach to the epithelial cell surface as microcolonies and induce dramatic changes to the host cell cortex. We tested the hypothesis that type IV pili (Tfp) retraction plays a role in the ultrastructure of both the host cell cortex and the bacterial microcolony. Using serial ultrathin sectioning, transmission electron microscopy and 3D reconstruction of serial 2D images, we have obtained what we believe to be the first 3D reconstructions of the N. gonorrhoeae-host cell interface, and determined the architecture of infected cell microvilli as well as the attached microcolony. Tfp connect both wild-type (wt) and Tfp retraction-deficient bacteria with each other, and with the host cell membrane. Tfp fibres and microvilli form a lattice in the wt microcolony and at its periphery. Wt microcolonies induce microvilli formation and increases of surface area, leading to an approximately ninefold increase in the surface area of the host cell membrane at the site of attachment. In contrast, Tfp retraction-deficient microcolonies do not affect these parameters. Wt microcolonies had a symmetrical, dome-shaped structure with a circular 'footprint', while Tfp retraction-deficient microcolonies were notably less symmetrical. These findings support a major role for Tfp retraction in microvilli and microcolony architecture. They are consistent with the biophysical attributes of Tfp and the effects of Tfp retraction on epithelial cell signalling.