Melania Ester Mercado-Pimentel
- Assistant Professor, Otolaryngology (Research Scholar)
Dr. Melania Mercado-Pimentel is a Molecular Cellular & Developmental Biologist graduated from The City University of New York. She is Assistant Professor at the College of Medicine of the University of Arizona. Her work has contributed to the research fields of developmental biology, benign tumors and cancer. Dr. Mercado-Pimentel’s doctoral dissertation was in developmental neurobiology, which aimed to understand the role that Hox genes play in the axon patterning during the development of the nervous system. Another of her graduate research projects focused in the role that molecules, expressed in glial cells of the optic path during optic nerve development, play in guiding the optic axons to connect to the right targets in the brain. Her postdoctoral training at the University of Arizona was in heart valve development. She studied the role that TGF-bs (endoglin and TGF-β receptor 1 or ALK5) play in the process of epithelial-mesenchymal transition (EMT) during heart valve formation. This project was key in her decision to study cancer progression and metastasis, since EMT is one of the first events to occur in the onset of metastasis. Subsequently, Dr. Mercado-Pimentel has been using her scientific training in basic research for the investigation of human diseases, such as colon cancer, vestibular schwannomas and meningiomas, and presently, oral squamous cell carcinoma.
- Ph.D. Molecular Cell and Developmental Biology
- The Graduate School and University Center of The City University of New York, New York, New York, United States
- The Leech Hox Gene LOX6 Plays a role in Nervous System Differentiation and Patterning
- M.A. Molecular Cellular and Developmental Biology
- The City College of the City University of New York, New York, New York, United States
- B.S. Biology
- York College of the CIty University of New York, Queens, New York, United States
- Assistant Professor (Research Scholar Track), Department of Otolaryngology- University of Arizona (2016 - Ongoing)
- Research Assistant Professor, University of Arizona - Department of Otolaryngology (2015 - 2016)
- Scientist, Ventana Medical Systems (2013 - 2014)
- Assistant Professor (Research Scholar Track), University of Arizona - Department of Pathology (2009 - 2013)
- Assistant Research Scientist, University of Arizona - Department of Pathology (2009)
- Assistant Research Scientist, University of Arizona - Department of Cellular and Molecular Medicine (2007 - 2008)
- Adjunct Lecturer, Northwest Pima Community College (2003 - 2004)
- Research Associate (Postdoctor), University of Arizona - Department of Cellular and Molecular Medicine (2002 - 2006)
- Adjunct Lecturer, Lehman College of The City University of New York (1999 - 2002)
- Adjunct Lecturer, Hostos Community College (1996 - 1998)
- Adjunct Lecturer, The City College of The City University of New York (1996 - 1998)
- The Faculty Stipend Award
- Office of Diversity and Inclusion- Arizona Center of Excellence, Spring 2016
- The Faculty Travel Award
- Office of Diversity and Inclusion/Arizona Center of Excellence, Spring 2015
Molecular and Cellular Biology,Developmental Biology
Molecular mechanisms of tumor growth, cancer progression and metastasis.Dr. Mercado-Pimentel's specific research interest is to understand how microRNAs regulate and are regulated during tumor growth and metastasis in oral squamous cell carcinoma.
Directed RsrchMCB 392 (Fall 2016)
Honors ThesisECOL 498H (Fall 2016)
Honors ThesisMCB 498H (Fall 2016)
Directed ResearchECOL 492 (Spring 2016)
Honors Independent StudyMCB 499H (Spring 2016)
Honors Independent StudyPSIO 399H (Spring 2016)
Directed ResearchECOL 392 (Fall 2015)
Directed RsrchMCB 492 (Fall 2015)
Directed RsrchMCB 492 (Summer I 2015)
- Mercado-Pimentel, M. E., Miller, C., Rolph, D. N., Villalobos, E. F., Dunn, A. M., Mohan, P. M., Igarashi, S., Liu, X., Yrun-Duffy, M., Patel, N. K., Read, C. M., Francis, R. H., Lane, A. I., Murugesh, S., & Jacob, A. (2017). Inhibiting p21-Activated Kinase Induces Cell Death in Vestibular Schwannoma and Meningioma via Mitotic Catastrophe. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 38(1), 139-146.More infop21-activated kinase (PAK) regulates signaling pathways that promote cell survival and proliferation; therefore, pharmacological inhibition of PAK will induce cell death in vestibular schwannomas (VS) and meningiomas.
- Mercado-Pimentel, M., & Jacob, A. (2016). The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation. Austin Journal of Medical Oncology, 3(1), 1025.
- 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.2015.07.010More infoS100P 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., Villalobos, E. F., Mohan, P. M., Reid, C. M., Ross, F., Rolph, D. N., & Jacob, A. (2016, May). Inhibiting p21-Activated Kinase Induces Cell Death in Vestibular Schwannoma and Meningioma via Mitotic Catastrophe. 51st Annual Spring Meeting American Neurotology Society. Chicago, IL: American Neurotology Society.More infoHypothesis: p21-Activated Kinase (PAK) regulates signaling pathways that promote cell survival and proliferation; therefore, pharmacological inhibition of PAK will induce cell death in vestibular schwannomas (VS) and meningiomas.Background: All VS and many meningiomas result from loss of the neurofibromatosis type 2 (NF2) gene product merlin, with ensuing PAK hyperactivation and increased cell proliferation/survival. Methods: The novel small molecule PAK inhibitors PI-8 and PI-15 - tested in schwannoma and meningioma cells - perturb molecular signaling and induce cell death. MTT, flow cytometry and TUNEL assay analyzed PAK inhibitors’ effect on cell viability, cell cycle and cell death, respectively. Western blots evaluated activation and expression of cell proliferation, apoptotic, and mitotic catastrophe markers while light microscopy evaluated cell morphology and immunohistochemistry analyzed cellular localization of phospho-Merlin. Results: Treatment with PI-8 and PI-15 decreased cell viability at 0.65-3.7 µM IC50 in schwannoma and meningioma cells. Treatment increased G1-phase by 4% and decreased S-phase by 3.5%. TUNEL and western blot for apoptotic markers found that both PAK inhibitors did not induce apoptosis; instead, the expression and activation of proliferation markers (aurora B and GSK-3β) known to play a role in microtubule length and chromosomal alignment/aggregation decreased after 48 hours treatment. PAK inhibitor treated cells stained for phospho-Merlin localized to over-duplicated centrosomes of dividing cells, multiple enlarged nuclei, and misaligned/missegregated chromosomes – markers for mitotic catastrophe. Increased ATG5 levels and caspases-2 activation confirmed this cell death type.Conclusion: PAK inhibitors induce cell death in schwannoma and meningioma cells, at least in part, by mitotic catastrophe.Define Professional Practice Gap & Educational Need: There are no drugs currently FDA approved for the treatment of vestibular schwannomas and meningiomas; therefore, the development of novel therapeutics represents an urgent and unmet clinical need.Learning Objectives: (1) To describe the mechanisms whereby loss of the neurofibromatosis type 2 gene product merlin results in hyperactivation of the p21-activated kinase; (2) to discuss the end biological effects of treating schwannoma and meningioma cells with the novel PAK inhibitors PI-8 and PI-15; and (3) to describe hallmarks of mitotic catastrophe and discuss evidence for this mechanism of cell death in cells treated with PAK inhibitors. Desired Result: To develop and translate PAK inhibitors as a viable treatment strategy for vestibular schwannomas and meningiomas.
- Mercado-Pimentel, M. E., Villalobos, E. F., Rolph, D. N., Yrun-Daffy, M., & Jacob, A. (2016, May). The Oncomir Mir-21 Facilitates AKT Pathway Activation in Vestibular Schwannomas and Meningiomas. 51st Annual Spring Meeting American Neurotology Society, COSM 2016. Chicago, IL: American Neurotology Society.More infoHypothesis: Overexpression of oncomir miR-21 in vestibular schwannomas (VS) represses tumor suppressor genes involved in the inhibition of the PI3K/AKT pathway.Background: MicroRNAs regulate gene expression at the post-transcriptional level by binding to the 3’-UTR of their targets. The oncomir (oncogene) miR-21 is up-regulated in different types of cancers during tumor growth inducing cell proliferation and inhibiting cell death. VS are caused by mutations in the neurofibromatosis type 2 (NF2) gene and activation of the PI3K/AKT signaling pathway drives VS tumor growth. PTEN, BTG2, and TIMP1 are targets of miR-21 and function as inhibitors of the PI3K/AKT pathway. Therefore, miR-21 may represent a putative target for VS therapy.Methods: Expression levels of miRNAs were analyzed by stem-loop quantitative Real Time PCR (qRT-PCR) based on SYBR-Green I. MirVana kit was used to isolate miRNA and RNA fractions. Expression of miRNA targets was analyzed by qRT-PCR. Protein expression of the miR21 targets was analyzed by western blots. MiRNA expression was normalized to the small RNA U6 while expression of miRNA targets was normalized to GAPDH.Results: High expression levels of miR-21 were found in VS and meningioma cells as well as in VS tumors compared to Schwann primary cell lines. Additionally, miR21 targets and tumor suppressors, PDCD4, BTG2, PTEN and TIMP1, were found in very low expression levels. Conclusion: MiR-21 over-expression supports VS tumor growth by inducing the AKT signaling pathway via the repression of PTEN, BTG2, TIMP1 and PDCD4. MiR-21 is a promising molecular target for the development of VS therapy.