Ritu Pandey

Interests

Research

Cancer Bioinformatics, Multi-Omics data analysis and interpretation, Integrative Omics, Translational BioinformaticsMolecular profiling of different tumor types to identify unique biomarkers and genetic characteristics of certain type. Our main interest is to analyze the information generated from to identify drug targets and therapies that work better.

Courses

Scholarly Contributions

Journals/Publications

• Lou, E., Xiu, J., Baca, Y., Saeed, A., Prakash, A., Gholami, S., Subramanian, S., Starr, T. K., Fontana, E., Pandey, R., Lenz, H. J., Shields, A. F., Nabhan, C., Oberley, M., Seeber, A., & El-Deiry, W. (2024). Differential landscape of immune evasion in oncogenic RAS-driven primary and metastatic colorectal cancers. Molecular therapy. Oncology, 32(1), 200786.
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  Oncogenic drivers such as extensively modulate the tumor inflammatory microenvironment (TIME) of colorectal cancer (CRC). The influence of on modulating immune cell composition remains unclear. The objective of this study was to identify signatures of infiltrative immune cells and distinctive patterns that differ between wild-type (WT) and oncogenic mutant (MT) CRC that explain immune evasion in MT tumors. A total of 7,801 CRC specimens were analyzed using next-generation DNA sequencing, whole-exome sequencing, and/or whole transcriptome sequencing. Deficiency of mismatch repair (dMMR)/microsatellite instability (MSI) and tumor mutation burden (TMB) were also assessed. mutations were present in 48% of CRC, similarly distributed in patients younger than vs. 50 years and older. In microsatellite stable (MSS) MT tumors, composition of the TIME included higher neutrophil infiltration and lower infiltration of B cells. MSI-H/dMMR was significantly more prevalent in WT (9.1%) than in MT (2.9%) CRC. In MSS CRC, TMB-high cases were significantly higher in RAS MT (3.1%) than in RAS WT (2.1%) tumors. and mutations are associated with increased neutrophil infiltration, with codon-specific differences. These results demonstrate significant differences in the TIME of mutant CRC that match previous reports of immunoevasive characteristics of such tumors.
• Morrison, C., Weterings, E., Gravbrot, N., Hammer, M., Weinand, M., Sanan, A., Pandey, R., Mahadevan, D., & Stea, B. (2024). Gene Expression Patterns Associated with Survival in Glioblastoma. International journal of molecular sciences, 25(7).
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  The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (, and ) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase ( promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank -value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank -value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.
• Subramani, B., Conway, P. J., Al-Khinji, A., Zhang, K., Pandey, R., & Mahadevan, D. (2024). A Novel Triplet of Alisertib Plus Ibrutinib Plus Rituximab Is Active in Mantle Cell Lymphoma. Cancers, 16(24).
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  : Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance. Alisertib plus ibrutinib was therapeutically synergistic on both Granta-519 insensitive to ibrutinib and JeKo-1 cells sensitive to ibrutinib. Alisertib decreased PI-3K, BTK, p38, HCK, and RSK kinases, indicative of its multipotent effect on cellular proliferation and growth. A mouse xenograft model of Granta-519 demonstrated that alisertib plus ibrutinib had a comparable anti-tumor response to ibrutinib plus rituximab. However, alisertib plus ibrutinib plus rituximab demonstrated significantly stronger tumor growth inhibition than the doublets. : Both double and triple combinations showed enhanced survival versus ibrutinib alone. Ibrutinib insensitivity can be disrupted by alisertib plus ibrutinib in MCL.
• Chakravarti, J., Pandey, R., Churko, J., Eschbacher, J., Mallick, S., Chen, Y., Hermes, B., Mallick, P., Stansfield, B., Pond, K. W., Thorne, C., Yuen, K., Little, A. S., & Zavros, Y. (2022). Development Of Human Pituitary Adenoma-Derived Organoids To Facilitate Effective Targeted Treatments Of Cushing's Disease.. Cells, 11(12).
• Wusterbarth, E., Chen, Y., Jecius, H., Krall, E., Runyan, R. B., Pandey, R., & Nfonsam, V. (2022). Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival. The Journal of surgical research, 270, 169-177.
• Pandey, R., Zhou, M., Chen, Y., Darmoul, D., Kisiel, C. C., Nfonsam, V. N., & Ignatenko, N. A. (2021). Molecular Pathways Associated with Kallikrein 6 Overexpression in Colorectal Cancer. Genes, 12(5).
• Rico, K., Duan, S., Pandey, R. L., Chen, Y., Chakrabarti, J. T., Starr, J., Zavros, Y., Else, T., Katona, B. W., Metz, D. C., & Merchant, J. L. (2021). Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours. BMJ open gastroenterology, 8(1).
• Singh, N., Ramnarine, V. R., Song, J. H., Pandey, R., Padi, S. K., Nouri, M., Olive, V., Kobelev, M., Okumura, K., McCarthy, D., Hanna, M. M., Mukherjee, P., Sun, B., Lee, B. R., Parker, J. B., Chakravarti, D., Warfel, N. A., Zhou, M., Bearss, J. J., , Gibb, E. A., et al. (2021). The long noncoding RNA H19 regulates tumor plasticity in neuroendocrine prostate cancer. Nature communications, 12(1), 7349.
• Larson, K. R., Kannaiyan, R., Pandey, R., Babiker, H., & Dark, M. (2020). A Comparative Analysis of Tumor and Plasma Circulating Tumor DNA in 145 Advanced Cancer Patients annotated by 3 Core Cellular Processes. Cancers.
• Pandey, R., Zhou, M., Islam, S., Chen, B., Barker, N. K., Langlais, P., Srivastava, A., Luo, M., Cooke, L. S., Weterings, E., & Mahadevan, D. (2019). Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target. Scientific reports, 9(1), 18347.
• Padi, S. K., Luevano, L., An, N., Pandey, R., Singh, N., Song, J., Aster, J., Yu, X., Mehrotra, S., & Kraft, A. S. (2017). Targeting the PIM Protein Kinases for the Treatment of a T-cell Acute Lymphoblastic Leukemia Subset. Oncotarget.
• Sells, E., Pandey, R., Chen, H., Skovan, B. A., Cui, H., & Ignatenko, N. A. (2017). Specific microRNA-mRNA regulatory network of colon cancer invasion regulated by tissue kallikrein-related peptidase 6. Neoplasia.
• Greenwood, E., Maisel, S., Ebertz, D., Russ, A., Pandey, R., & Schroeder, J. (2016). Llgl1 prevents metaplastic survival driven by epidermal growth factor dependent migration. Oncotarget, 7(38), 60776-60792.
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  We have previously demonstrated that Llgl1 loss results in a gain of mesenchymal phenotypes and a loss of apicobasal and planar polarity. We now demonstrate that these changes represent a fundamental shift in cellular phenotype. Llgl1 regulates the expression of multiple cell identity markers, including CD44, CD49f, and CD24, and the nuclear translocation of TAZ and Slug. Cells lacking Llgl1 form mammospheres, where survival and transplantability is dependent upon the Epidermal Growth Factor Receptor (EGFR). Additionally, Llgl1 loss allows cells to grow in soft-agar and maintain prolonged survival as orthotopic transplants in NOD-SCIDmice. Lineage tracing and wound healing experiments demonstrate that mammosphere survival is due to enhanced EGF-dependent migration. The loss of Llgl1 drives EGFR mislocalization and an EGFR mislocalization point mutation (P667A) drives these same phenotypes, including activation of AKT and TAZ nuclear translocation. Together, these data indicate that the loss of Llgl1 results in EGFR mislocalization, promoting pre-neoplastic changes.
• Baker, A. F., Malm, S. W., Pandey, R., Laughren, C., Cui, H., Roe, D., & Chambers, S. K. (2015). Evaluation of a hypoxia regulated gene panel in ovarian cancer. Cancer microenvironment : official journal of the International Cancer Microenvironment Society, 8(1), 45-56.
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  A panel of nine hypoxia regulated genes, selected from a previously published fifty gene panel, was investigated for its ability to predict hypoxic ovarian cancer phenotypes. All nine genes including vascular endothelial growth factor A, glucose transporter 1, phosphoglycerate mutase 1, lactate dehydrogenase A, prolyl 4-hydroxylase, alpha-polypeptide 1, adrenomedullin, N-myc downstream regulated 1, aldolase A, and carbonic anhydrase 9 were upregulated in the HEY and OVCAR-3 human ovarian cell lines cultured in vitro under hypoxic compared to normoxic conditions as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene panel was also elevated in HEY xenograft tumor tissue compared to HEY cells cultured in normoxia. The HEY xenograft tissue demonstrated heterogeneous positive immunohistochemical staining for the exogenous hypoxia biomarker pimonidazole, and the hypoxia regulated protein carbonic anhydrase IX. A quantitative nuclease protection assay (qNPA) was developed which included the nine hypoxia regulated genes. The qNPA assay provided similar results to those obtained using qRT-PCR for cultured cell lines. The qNPA assay was also evaluated using paraffin embedded fixed tissues including a set of five patient matched primary and metastatic serous cancers and four normal ovaries. In this small sample set the average gene expression was higher in primary and metastatic cancer tissue compared to normal ovaries for the majority of genes investigated. This study supports further evaluation by qNPA of this gene panel as an alternative or complimentary method to existing protein biomarkers to identify ovarian cancers with a hypoxic phenotype.