Angel C Pimentel

Interests

Research

As part of my completion of my Master's Degree, I am in the process of initial research study to better understand the participation of students with physical and sensory disabilities in STEM field at UArizona.

Teaching

Introductory Biology (MCB 181)Bioethics (MCB 404)Evolution of Modern Biology (MCB 170c1)

Courses

Scholarly Contributions

Journals/Publications

• Shamloula, H. K., Mbogho, M. P., Pimentel, A. C., Chrzanowska-Lightowlers, Z. M., Hyatt, V., Okano, H., & Venkatesh, T. (2002). rugose (rg), a Drosophila A kinase Anchor Protein, Is Required for Retinal Pattern Formation and Interacts Genetically With Multiple Signaling Pathways. Genetics, 161(2), 693–710. doi:10.1093/genetics/161.2.693
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  Abstract In the developing Drosophila eye, cell fate determination and pattern formation are directed by cell-cell interactions mediated by signal transduction cascades. Mutations at the rugose locus (rg) result in a rough eye phenotype due to a disorganized retina and aberrant cone cell differentiation, which leads to reduction or complete loss of cone cells. The cone cell phenotype is sensitive to the level of rugose gene function. Molecular analyses show that rugose encodes a Drosophila A kinase anchor protein (DAKAP 550). Genetic interaction studies show that rugose interacts with the components of the EGFR- and Notch-mediated signaling pathways. Our results suggest that rg is required for correct retinal pattern formation and may function in cell fate determination through its interactions with the EGFR and Notch signaling pathways.
• Jandova, J., Li, Q. V., Mercado-Pimentel, M. E., Nelson, M. A., Onyeagucha, B. C., & Pimentel, A. C. (2015). The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells. FEBS Letters, 18, 2388-2393. doi:10.1016/j.febslet.2015.07.010
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  S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter.
• Mercado-Pimentel, M. E., Onyeagucha, B. C., Li, Q., Pimentel, A. C., Jandova, J., & Nelson, M. A. (2015). Research Article: The S100P/RAGE-Receptor Signaling Regulates Expression of microRNA-21 in colon cancer cells. FEBS Letters, 589(18), 2388-2393. doi:10.1016/j.febslet.2015.07.010
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  S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter.
• Pimentel, A. C., Pimentel, A. C., Onyeagucha, B. C., Nelson, M. A., Mercado-pimentel, M. E., & Li, Q. V. (2012). Abstract 2398: S100P/RAGE signaling activates AP1 and NF-kB in miR-21/RECK regulation. Cancer Research, 72, 2398-2398. doi:10.1158/1538-7445.am2012-2398
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  Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The receptor for advanced glycation end-products (RAGE) plays a role in different pathological diseases including cancer. Several ligands activate RAGE, among them are AGEs (advance glycation end-products), HMGB1 (amphoterin), amyloid-α peptide, and the S100 Ca2+ binding family. Activation of RAGE by S100P stimulates many cell processes in cancer mediated by AP1, NF-kB and ERK1/2. Recently, these transcription factors were shown to induce expression of the oncogene, miR-21. Our data show that S100P over-expression in LS174T and SW480 colon cancer cells induces miR-21 expression. It is well known that S100P has an intracellular and an extracellular function when it interacts with Ezrin and RAGE respectively. To decipher if the extracellular function of S100P mediated by its interaction with RAGE induces miR-21, we treated SW480 normally expressing RAGE and not S100P with exogenous human recombinant (hr)-S100P. These results show that S100P/RAGE signaling induces miR-21 expression. To determine if the induction of miR-21 by S100P/RAGE signaling is mediated by AP1 and NF-kB, we performed luciferase studies with wild type, and mutated AP1 and NF-kB pri-miR-21 promoter constructs in cells expressing only the RAGE receptor. These data show that S100P/RAGE signaling mediates miR-21 induction by the activation of AP1 and NF-kB. Additionally, LS174T cells expressing RAGE and S100P rendered similar results when they ectopically over-express S100P. However, ectopic S100P expression in SW480 cells induced miR-21 independent of AP1 and NF-kB. These results suggest that S100P has another mechanism of regulating miR-21. Our previous data indicated that over-expression of S100P down regulates the reversion-inducing cysteine-rich protein with Kazal motifs (RECK). RECK is an anti metastatic gene, inhibitor of metalloproteinases and a target of miR-21. Our data shows that RAGE expressing cells treated with exogenous hr-S100P down regulate RECK expression, suggesting that miR-21 induction by S100P/RAGE signaling represses RECK. To determine if there is a correlation in expression levels of miR-21 with RECK, RAGE, and S100P, we used the combined method of in situ hybridization (ISH) and immunohistochemical (IHC) techniques on human colorectal cancer tissues. We found that there are three groups of cells in the malignant epithelium as well as in the surrounding tissue. One group of cells expresses high levels of miR-21, another group expresses high levels of RECK while the third group expresses both. Together, these data show that S100P/RAGE regulates miR-21/RECK expression mediated by AP1 and NF-kB and suggest that in cancer this signaling pathway remodels the extracellular matrix by the activation of metalloproteinases inducing epithelial mesenchymal transition to allow cell migration/invasion in colon cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2398. doi:1538-7445.AM2012-2398
• Das, S., Dervan, A., Gandhi, A., Heidari, R., Holohan, E. E., Ito, K., Larkin, A., Lee, J. A., Pimentel, A., Priya, R., Ramaswami, M., Rodrigues, V., Sadanandappa, M. K., Sanyal, S., Sudhakaran, I. P., & Wang, J. W. (2011). Plasticity of local GABAergic interneurons drives olfactory habituation. Proceedings of the National Academy of Sciences, 108(36). doi:10.1073/pnas.1106411108
• Fermin, H. A., Hyatt, V. J., Kaplow, M. E., Lee, J. J., Mannava, L. J., Pimentel, A. C., & Venkatesh, T. R. (2007). A genetic modifier screen identifies multiple genes that interact with Drosophila Rap/Fzr and suggests novel cellular roles.. Journal of neurogenetics, 21(3), 105-51. doi:10.1080/01677060701503140
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  In the developing Drosophila eye, Rap/Fzr plays a critical role in neural patterning by regulating the timely exit of precursor cells. Rap/Fzr (Retina aberrant in pattern/Fizzy related) is an activator of the E3 Ubiquitin ligase, the APC (Anaphase Promoting Complex-cyclosome) that facilitates the stage specific proteolytic destruction of mitotic regulators, such as cyclins and cyclin-dependent kinases. To identify novel functional roles of Rap/Fzr, we conducted an F(1) genetic modifier screen to identify genes which interact with the partial-loss-function mutations in rap/fzr. We screened 2741 single P-element, lethal insertion lines and piggyBac lines on the second and third chromosome for dominant enhancers and suppressors of the rough eye phenotype of rap/fzr. From this screen, we have identified 40 genes that exhibit dosage-sensitive interactions with rap/fzr; of these, 31 have previously characterized cellular functions. Seven of the modifiers identified in this study are regulators of cell cycle progression with previously known interactions with rap/fzr. Among the remaining modifiers, 27 encode proteins involved in other cellular functions not directly related to cell-cycle progression. The newly identified variants fall into at least three groups based on their previously known cellular functions: transcriptional regulation, regulated proteolysis, and signal transduction. These results suggest that, in addition to cell cycle regulation, rap/fzr regulates ubiquitin-ligase-mediated protein degradation in the developing nervous system as well as in other tissues.
• Pimentel, A. C., & Venkatesh, T. (2005). rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and pattern formation in the developing Drosophila eye-antennal disc. Developmental Biology, 285(2), 436-446. doi:10.1016/j.ydbio.2005.07.011
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  The rap (retina aberrant in pattern) gene encodes the Fizzy-related protein (Fzr), which as an activator of the ubiquitin ligase complex; APC/C (anaphase promoting complex/cyclosome) facilitates the cell cycle stage-specific degradation of cyclins. Loss-of-function mutations in rap cause unscheduled accumulation of cyclin B in the developing eye imaginal disc, resulting in additional mitotic cycles and defective patterning of the developing Drosophila eye. Targeted mis-expression of rap/fzr in the eye primordial cells causes precocious cell cycle exit, and smaller primordial eye fields, which either eliminate or drastically reduce the size of the adult eye. Although mitosis is inhibited in the mis-expression animals, cells with abnormally large nuclei form tumor-like structures from continued endoreplication, cell growth and retinal differentiation. Interestingly, overexpression of Rap/Fzr in the eye primordia also increases the size of the antennal primordium resulting in the induction of ectopic antennae. These results suggest that Rap/Fzr plays an essential role in the timely exit of precursor cells from mitotic cycles and indicate that mechanisms that regulate cell cycle exit are critical during pattern formation and morphogenesis.
• Karpilow, J., Pimentel, A. C., Shamloula, H. K., & Venkatesh, T. (1996). Neuronal development in the Drosophila compound eye: Photoreceptor cells R1, R6, and R7 fail to differentiate in the retina aberrant in pattern (rap) mutant. Developmental Neurobiology, 31(2), 149-165. doi:10.1002/(sici)1097-4695(199610)31:2<149::aid-neu2>3.3.co;2-y
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  The compound eye of Drosophila is a reiterated pattern of 800 unit eyes known as ommatidia. In each ommatidium there are eight photoreceptor neurons (R1–R8) and an invariant number of accessory cells organized in a precise manner. In the developing eye, specification of cell fates is triggered by sequential inductive events mediated by cell-cell interactions. The R8 photoreceptor neuron is the first cell to differentiate and is thought to play a central role in the recruitment of the remaining photoreceptor cells. Our previous work demonstrated that mutations in the retina aberrant in pattern (rap) locus lead to abnormal pattern formation in the compound eye. Genetic mosaic experiments demonstrated that for normal retinal patterning to occur, rap gene function is required only in the photoreceptor cell R8. In this study we analyzed the R cell composition of developing as well as the adult eyes of rap mutants employing a variety of R cell specific markers. We show that in rap mutants, although some of the R8-specific markers show normal expression patterns, other aspects of the R8 cell differentiation are abnormal. In addition, the cells R1, R6, and R7 fail to differentiate properly in rap mutants. These results suggest that the rap gene encodes an R8-specific function that plays a role in the determination of the photoreceptor cells R1, R6, and R7. © 1996 John Wiley & Sons, Inc.