Papers by Keith Fernandez
Bachelor'sBachelor of Arts (Honours
This Note is brought to you for free and open access by the Law Reviews and Journals at LSU Law D... more This Note is brought to you for free and open access by the Law Reviews and Journals at LSU Law Digital Commons. It has been accepted for inclusion in Louisiana Law Review by an authorized editor of LSU Law Digital Commons. For more information, please contact kreed25@lsu.edu.
ABSTRACTDuring the development of humoral immunity, activated B lymphocytes undergo vigorous prol... more ABSTRACTDuring the development of humoral immunity, activated B lymphocytes undergo vigorous proliferative, transcriptional, metabolic, and DNA remodeling activities; hence, their genomes are constantly exposed to an onslaught of genotoxic agents and processes. Recombination-dependent DNA transactions that preserve the integrity of the genome and of the DNA replication process generates Holliday junctions that must be eliminated for the accurate segregation of sister chromatids and faithful propagation of genomic material. To investigate the role of two Holliday junction resolvases, GEN1 and MUS81, in B cell biology, we established B-cell conditional knockout mouse models and found that targeted deletion of GEN1 and MUS81 in early B cell precursors halts their development and maturation while selective loss of the resolvases in mature B cells inhibits the generation of robust germinal centers. Upon activation, these double-null mature B lymphocytes fail to proliferate and survive wh...
Frontiers in Immunology, 2022
Frontiers in Immunology, 2021
Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple phys... more Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In ad...
Immunity, 2020
Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci prom... more Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation (SHM), whereas AID targeting of non-Ig loci can generate oncogenic DNA lesions. Here, we examined the contribution of G-quadruplex (G4) nucleic acid structures to AID targeting in vivo. Mice bearing a mutation in Aicda (AIDG133V) that disrupts AID-G4 binding modeled the pathology of hyper-IgM syndrome patients with an orthologous mutation, lacked CSR and SHM, and had broad defects in genome-wide AIDG133V chromatin localization. Genome-wide analyses also revealed that wild-type AID localized to MHCII genes, and AID expression correlated with decreased MHCII expression in germinal center B cells and diffuse large B cell lymphoma. Our findings indicate a crucial role for G4 binding in AID targeting and suggest that AID activity may extend beyond Ig loci to regulate the expression of genes relevant to the physiology and pathology of activated B cells.
SummaryIntracellular bacterial pathogens inject effector proteins into host cells to hijack diver... more SummaryIntracellular bacterial pathogens inject effector proteins into host cells to hijack diverse cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32Salmonella entericaserovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effector proteins, and quantified PPIs in macrophages and epithelial cells by Affinity-Purification Quantitative Mass-Spectrometry. Thereby, we identified 25 previously described and 421 novel effector-host PPIs. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. Using reciprocal co-immunoprecipitations, we validated 13 out of 22 new PPIs. We then used this host-pathogen physical interactome resource to demonstrate that SseJ and SseL collaborate in redirecting cholesterol to theSalmonellaContaining Vacuole (SCV) via NPC1, PipB...
Science, 2020
Ironing out the details of mucosal healing Anemia is a frequent complication of disorders such as... more Ironing out the details of mucosal healing Anemia is a frequent complication of disorders such as inflammatory bowel disease, occurring in part as a result of increased bleeding into the intestine. Bessman et al. show that the peptide hormone hepcidin, which regulates systemic iron homeostasis, is required for intestinal repair in a mouse model of inflammatory bowel disease (see the Perspective by Rescigno). This effect was independent of hepatocyte-produced hepcidin and systemic iron levels. Instead, production of hepcidin by conventional dendritic cells was necessary and sufficient to promote local iron sequestration by macrophages, which in turn modulated the makeup of the gut microbiota to one with a more beneficial distribution of species. Science , this issue p. 186 ; see also p. 129
Studies in Conservation, 1994
Philippines Manila. She is also a Registered Microbiologist, serves as a part-time Lecturer in th... more Philippines Manila. She is also a Registered Microbiologist, serves as a part-time Lecturer in the Medical Microbiology Department of the same university. She also serves as a Research Assistant in the study entitled "Developing strategies to promote engagement in HIV care", a collaborative project between
Cell Reports, 2019
Sundaravinayagam et al. (2019) uncovered a critical role of 53BP1 in class switch recombination i... more Sundaravinayagam et al. (2019) uncovered a critical role of 53BP1 in class switch recombination in B cells beyond its role in limiting end resection.
The Journal of Immunology, 2019
Nature, Jan 29, 2018
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microb... more A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future resea...
Language in Society, 2017
Children acquiring sociolinguistic knowledge in transnational migration settings must learn to ev... more Children acquiring sociolinguistic knowledge in transnational migration settings must learn to evaluate multiple languages and dialects in a fluid, multifaceted social landscape. This study examines the sociolinguistic development of local and expatriate children in Singapore and investigates the extent to which they share sociolinguistic knowledge and norms. One hundred fourteen children ages five to nineteen completed a region identification task and an occupation judgment task, focusing on their perception of four regional English varieties: Australian English, Northern-China-accented English, Filipino English, and Singapore English. While all groups performed well on the region identification task, expatriate children outperformed locals within the youngest age group. Singaporean and expatriate children attending local schools showed greater familiarity with local norms than international school students in their occupation ratings. Participants mapped speakers to occupations by...
Scientific reports, Jan 16, 2015
Helicobacter pylori at multiplicity of infection (MOI ≥ 50) have been shown to cause apoptosis in... more Helicobacter pylori at multiplicity of infection (MOI ≥ 50) have been shown to cause apoptosis in RAW264.7 monocytic macrophage cells. Because chronic gastric infection by H. pylori results in the persistence of macrophages in the host's gut, it is likely that H. pylori is present at low to moderate, rather than high numbers in the infected host. At present, the effect of low-MOI H. pylori infection on macrophage has not been fully elucidated. In this study, we investigated the genome-wide transcriptional regulation of H. pylori-infected RAW264.7 cells at MOI 1, 5 and 10 in the absence of cellular apoptosis. Microarray data revealed up- and down-regulation of 1341 and 1591 genes, respectively. The expression of genes encoding for DNA replication and cell cycle-associated molecules, including Aurora-B kinase (AurkB) were down-regulated. Immunoblot analysis verified the decreased expression of AurkB and downstream phosphorylation of Cdk1 caused by H. pylori infection. Consistently...
This Note is brought to you for free and open access by the Law Reviews and Journals at LSU Law D... more This Note is brought to you for free and open access by the Law Reviews and Journals at LSU Law Digital Commons. It has been accepted for inclusion in Louisiana Law Review by an authorized editor of LSU Law Digital Commons. For more information, please contact kreed25@lsu.edu.
Students & Coyotes Instruction in Pedagogy & Performance (SCIPP) is a creative partnership betwee... more Students & Coyotes Instruction in Pedagogy & Performance (SCIPP) is a creative partnership between California State University San Bernardino (CSUSB) students and San Bernardino City and Riverside City elementary schools. SCIPP was developed by CSUSB Award-Winning Professor Juan Delgado and Manuel A. Salinas Elementary Master Teachers William Beshears and Larry Light and is currently under the coordination of CSUSB Professor Kelly (KL) Straight Dortch, Liberal Studies Programs Coordinator, Department of English Faculty, SCIPP Charter Member and Coordinator. Visit us at www.scipp.org for more information. SCIPP's Mission SCIPP redefines and expands the existing notions about what makes for a vibrant and robust community of practice by partnering CSUSB students and professors with K-12 students, parents, and educators, along with committed community partners. SCIPP encourages curiosity in ways that leads to critical thinking, exploration, "risk taking", confidence building, open-mindedness, and other personal traits that equip them with the softskills to be active, critical, and creative contributors to our communities. SCIPP pedagogy embraces our students' collective wisdom and focuses on relational building where multidirectional communication is promoted and students are viewed as equal stakeholders in their own educations. SCIPP puts collaboration into action which in turn fosters community-based lifelong learning. SCIPP provides the open intellectual space for future university students (our K-12 students) to engage with existing university students in meaningful ways so as to sustain interconnected partnerships facilitating community engagement. It supports parents as experts in the education of their children and acknowledges parents as the first conduits to spark their children's imagination while they actively participate in education enriching activities and programs. Everyone involved is committed to creating a secure and open atmosphere for dreaming, sharing, and learning. Together we explore the aspects of community publishing through collaborative learning in formal and informal settings relating to digital and printed medias. EXPANDED COMMUNITY OF PRACTICE MEMBERS The Events and Meetings Calendar included at the end of this document highlight the participation of the individuals listed here. Varying combinations of individuals came together during each occurrence and smaller group or individual meetings with Coordinator Dortch are specified under the Event Title. SCIPP Events would not be possible without the participation of all the families, students, and facilitators involved in bringing our community to life.
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Papers by Keith Fernandez