Vijay Setaluri, PHD

Pubmed

More information:

• Dr. Setaluri’s Molecular & Environmental Toxicology Center webpage

Research Description:

Tumor heterogeneity is a significant challenge in prognosis and management of patients with cancer. This problem is acute in melanoma skin cancer, which is thought to arise from the neural crest-derived, differentiated melanocytes in the skin.

Melanomas display characteristics of differentiation along a variety of cell types including neuronal cells. Two hypotheses have been proposed to explain this heterogeneity:

1. dedifferentiation of malignant melanocyte and transdifferentiation, and

2. malignant transformation of pluripotent skin resident (neural crest) stem cells that retain plasticity to differentiate along multiple pathways.

Support for the latter possibility has been gaining steadily since the discovery and description of human cancer cells bearing stem cell properties. Based on the consensus definition of a cancer stem cell as a cell within a tumor that is able to self-renew and promote heterogeneous lineages of cancer cells that make up the tumor, our data on the heterogeneity and neuronal differentiation of melanoma also points to involvement of stem cells in the development of melanoma.

Melanoma-derived iPSC as model for tumor cell plasticity & emergence of drug resistance

Selected References:

• Castro-Pérez, Singh, M., Sadangi, S., Mela-Sánchez, C., Setaluri, V. (2022) Connecting the Dots: Melanoma cell of origin, tumor cell plasticity, trans-Differentiation, and drug resistance. Pigment Cell & Melanoma Research, submitted
• Krishnan, A., Bhasker, A. I., Singh, M., Rodriguez, C., Castro-Perez, E., Altameemi, S.,  Lares, M., Khan, H., Ndiaye, M., Ahmad, N., Schieke, S., Setaluri, V. (2022) . EPAC Regulates Growth of Primary Melanoma Cells by Stimulating mTORC1 Signaling and Loss of Dependence on EPAC Signaling Correlates with Melanoma Progression. Molecular Cancer Research doi: 10.1158/1541-7786.MCR-22-0026. Online ahead of print.
• Singh, M. K., Altameemi, S.,  Lares, M., Newton, M. A., Setaluri, V. (2022) Role of dual specificity phosphatases (DUSPs) in melanoma cellular plasticity and drug resistance. Scientific Reports 12(1):14395. doi: 10.1038/s41598-022-18578-x.
• Castro-Pérez, E., Rodriguez, C. I., Mikheil, D., Newton, M. A., Siddique, A., McCarthy, A., and Setaluri, V. (2019) Melanoma Tumor Progression Inhibits Pluripotency and Melanoma-Derived iPSC Differentiate Predominantly to Neural-like Cells.  Stem Cell Reports 13:177-192