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Last Updated: 2021-10-07
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45
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Works (45)
41. Targeting the PI3 K-mTOR Signaling Circuitry in HPV-Associated Oral Malignancies: Novel Precision Molecular Therapies
- Title Tesim:
- Targeting the PI3 K-mTOR Signaling Circuitry in HPV-Associated Oral Malignancies: Novel Precision Molecular Therapies
- Creator:
- Doci, Colleen L. and Gutkind, J. Silvio
- Related Url Tesim:
- https://link.springer.com/chapter/10.1007/978-3-319-21100-8_7
- Description:
- HPV is the most common sexually transmitted infection and it is predicted that up to 80 % of Americans will have HPV infections in their lifetime. The etiology of cervical cancer has long been linked with persistent HPV infection, but the correlation between HPV and other cancer types, including head and neck squamous cell carcinomas (HNSCC), oropharyngeal carcinomas (OPCs), anal carcinomas, and cancers of the genital tract is emerging (Forman et al. Compared to alcohol- and tobacco-related HNSCC, HPV-associated head and neck cancer involves activation of specific molecular mechanisms, making HPV(+) HNSCCs diagnostically and therapeutically distinct. Here, we will review the current understanding of the molecular mechanisms in HPV(+) HNSCC with emphasis on the signaling events that drive the growth of HPV-associated HNSCC and the emerging opportunities for the development of novel precision molecular-targeted therapies for this disease.
- Rights statement:
- http://rightsstatements.org/vocab/InC/1.0/
- Language:
- English
- Publisher:
- Springer
- Identifier:
- 978-3-319-21100-8
- Type:
- Book
- Keyword:
- Oral Cancer Risk Factor, mTOR Pathway Activation, mTORC1 Complex, Oral Cancer, and mTOR Pathway
- Date Created:
- 2015
42. Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging
- Title Tesim:
- Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging
- Abstract Tesim:
- Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans (N2) and three long-lived mutants (daf-2, eat-2, and asm-3) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. We found host age is a better predictor of the E. coli expression profiles than host genotype. Specifically, host age was associated with clustering (permutational multivariate analysis of variance [PERMANOVA], P = 0.001) and variation (Adonis, P = 0.001, R2 = 11.5%) among E. coli expression profiles, whereas host genotype was not (PERMANOVA, P > 0.05; Adonis, P > 0.05, R2 = 5.9%). Differential analysis of the E. coli transcriptome yielded 22 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 100 KEGG genes enriched when samples were grouped by time point [LDA, linear discriminant analysis; log(LDA), ≥2; P ≤ 0.05], including several involved in biofilm formation. Coexpression analysis of host and bacterial genes yielded six modules of C. elegans genes that were coexpressed with one bacterial regulator gene over time. The three most significant bacterial regulators included genes relating to biofilm formation, lipopolysaccharide production, and thiamine biosynthesis. Age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, building on a growing literature of host-microbial interactions. IMPORTANCE Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans, including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans. The manuscript represents the first study, to our knowledge, to perform temporal host-microbial transcriptomics in the model organism C. elegans. Understanding changes to the microbial transcriptome over time is an important step toward elucidating host-microbial interactions and their potential relationship to aging. We found that age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, which contributes to our growing knowledge about host-microbial interactions.
- Creator:
- Brycky, J, Brislawn, C, Chan, Jason, Heibeck, N, Letson, G, Buonaccorsi, V, Unverdorben, L, Emlet, C, Chen See, J, and Lamendella, R
- Related Url Tesim:
- Available from Publisher: https://journals.asm.org/doi/10.1128/Spectrum.00498-21, Available from Library Catalog: https://marianunivindianapolis.on.worldcat.org/v2/oclc/9247923366, and Available from Pubmed: https://pubmed.ncbi.nlm.nih.gov/34523995/
- Rights statement:
- http://rightsstatements.org/vocab/InC/1.0/
- Language:
- English
- Publisher:
- ASM Journals
- Identifier:
- PMID: 34523995 and DOI: https://doi.org/10.1128/Spectrum.00498-21
- Type:
- Article
- Keyword:
- bacteria, Escherichia coli, microbiome, aging, Caenorhabditis elegans, and transcriptomics
- Date Created:
- 2021
43. Transcriptional signature primes human oral mucosa for rapid wound healing.
- Title Tesim:
- Transcriptional signature primes human oral mucosa for rapid wound healing.
- Creator:
- Onaitis, Mark W., Asselin-Labat, Marie-Liesse, Gutkind, J. S., Uchiyama, Akihiko, Callejas-Valera, Juan Luis, Abusleme, Loreto, Molinolo, Alfredo A., Edwards, Dean, Moutsopoulos, Niki M., Iglesias-Bartolome, Ramiro, Morasso, Maria I., Doci, ColleenL., and Brooks, Stephen R.
- Related Url Tesim:
- Original Article in Science Tranlational Medicine can be found here: https://stm.sciencemag.org/content/10/451/eaap8798 and https://www.ncbi.nlm.nih.gov/pubmed/30045979
- Description:
- Oral mucosal wound healing has long been regarded as an ideal system of wound resolution. However, the intrinsic characteristics that mediate optimal healing at mucosal surfaces are poorly understood, particularly in humans. We present a unique comparative analysis between human oral and cutaneous wound healing using paired and sequential biopsies during the repair process. Using molecular profiling, we determined that wound-activated transcriptional networks are present at basal state in the oral mucosa, priming the epithelium for wound repair. We show that oral mucosal wound-related networks control epithelial cell differentiation and regulate inflammatory responses, highlighting fundamental global mechanisms of repair and inflammatory responses in humans. The paired comparative analysis allowed for the identification of differentially expressed SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1) transcriptional regulators in oral versus skin keratinocytes, conferring a unique identity to oral keratinocytes. We show that SOX2 and PITX1 transcriptional function has the potential to reprogram skin keratinocytes to increase cell migration and improve wound resolution in vivo. Our data provide insights into therapeutic targeting of chronic and nonhealing wounds based on greater understanding of the biology of healing in human mucosal and cutaneous environments.
- Rights statement:
- http://rightsstatements.org/vocab/InC/1.0/
- Language:
- English
- Identifier:
- 10.1126/scitranslmed.aap8798
- Type:
- Article
- Keyword:
- paired and sequential biopsies, wound resolution, transcriptional networks, and Oral mucosal wound healing
- Date Created:
- 2018
44. Using Heterologous COS-7 Cells to Identify Semaphorin-Signaling Components.
- Title Tesim:
- Using Heterologous COS-7 Cells to Identify Semaphorin-Signaling Components.
- Creator:
- Doci, Colleen L., Gutkind, J. Silvio, and Sakurai, Atsuko
- Related Url Tesim:
- https://link.springer.com/protocol/10.1007%2F978-1-4939-6448-2_11 and https://pubmed.ncbi.nlm.nih.gov/27787849/
- Description:
- Semaphorins are a family of membrane-bound and secreted type of proteins which were initially identified as chemorepulsive axon guidance molecules. Plexins and neuropilins are two major receptor families of semaphorins, and their common downstream targets are the actin cytoskeleton and cell-to-extracellular matrix adhesions. Semaphorins promote the collapse of growth cones by inducing rapid changes in the cytoskeleton and disassembly of focal adhesion structures. When transfected with appropriate receptors, non-neuronal COS-7 cells exhibit a similar cell collapse phenotype upon semaphorin stimulation. This heterologous system using COS-7 cells has been developed and widely used to investigate semaphorin-signaling pathways. In this chapter, we describe a COS-7 collapse assay protocol used to identify semaphorin-signaling components and a method to produce recombinant class 3 semaphorin proteins.
- Rights statement:
- http://rightsstatements.org/vocab/InC/1.0/
- Language:
- English
- Publisher:
- Springer
- Identifier:
- PMID: 27787849 and 10.1007/978-1-4939-6448-2_11
- Type:
- Article
- Keyword:
- Culture Media, Neuropilins, Signal Transduction, Semaphorins, COS Cells, HEK293 Cells, and Cercopithecus aethiops
- Date Created:
- 2017
45. Vitamin C as a Model for a Novel and Approachable Experimental Framework for Investigating Spectrophotometry
- Title Tesim:
- Vitamin C as a Model for a Novel and Approachable Experimental Framework for Investigating Spectrophotometry
- Creator:
- Timmerman, K. M., Doci, C. L., Main, K. A., Angarita, P. A., Wilson, K. J., Gabbard, D. B., and Kinkade, K.B.
- Related Url Tesim:
- MU users may access this article here: https://marianunivindianapolis.on.worldcat.org/oclc/8599771077 and https://doi.org/10.1021/acs.jchemed.9b00197
- Description:
- This laboratory experiment, designed for undergraduate nonmajors or advanced high school students, attempts to demystify the technique of spectrophotometry by utilizing a hands-on, real-world approach. Modification of the reaction for the formation of Fe[(bpy)3]2+ allows students to interact with vitamin C, a compound with which they are familiar from daily life, and observe its concentration in an approachable experimental framework. These connections are emphasized in a protocol designed to help students correlate visual and quantitative data by generating their own standard curve against which they compare unknown solutions. This experiment was found to decisively increase students’ understanding of concepts related to standard curves and spectrophotometry, and it also demonstrated gains in student understanding of solubility and its impact on colorimetry. Opportunities within this experimental framework exist for additional conceptual development related to the chemical, technological, and social aspects of the assay. Combined with its pedagogical effectiveness, this represents an excellent resource for diverse chemistry classrooms.
- Rights statement:
- http://rightsstatements.org/vocab/InC/1.0/
- Language:
- English
- Publisher:
- American Chemical Society
- Identifier:
- 10.1021/acs.jchemed.9b00197
- Type:
- Article
- Keyword:
- Interdisciplinary/Multidisciplinary, Nonmajor Courses, Spectroscopy, Aqueous Solution Chemistry, Solutions/Solvents, Laboratory Instruction, Nutrition, First-Year Undergraduate/General, Hands-on Learning, and Analytical Chemistry
- Date Created:
- 2019