Madhu-1
 Madhusudan Dey
Assistant Professor
Molecular Biology

Office: Lapham 460
Phone: 414-229-4309
FAX: 414-229-3926
Email: deym@uwm.edu

RESEARCH INTERESTS

Almost one-third of total cellular proteins folds and matures in the endoplasmic reticulum (ER). Cellular perturbation (e.g., metabolic disorder and/or pathogen infection) causes an over-accumulation of unfolded proteins, a state referred to as the ER stress. ER stress initiates a network of signaling pathways, collectively called the unfolded protein response (UPR) that enhances the protein-folding capacity of the ER and provides strategies for adaptation to cellular perturbations. Defects in the UPR leads to many human diseases, including diabetes, arthritis and certain cancers. Our long-term goal is to fully understand the molecular basis the UPR pathway.

Two major components of the UPR are: a dual kinase RNase Ire1 and a transcription factor Hac1 in yeast or Xbp1 in human cells. Under conditions of ER stress, Ire1 cleaves specifically the HAC1/XBP1 mRNA to remove an inhibitory intron. The matured HAC1/XBP1 mRNA then yields Hac1/Xbp1 protein that activates the expression of UPR genes. We are interested in deciphering the specificity in HAC1/XBP1 mRNA cleavage by Ire1-RNase and the molecular mechanisms of translational repression of HAC1 mRNA. Recently, we have discovered the existence of a novel Kin kinase-signaling pathway in the yeast UPR, and have focused on elucidating the cross talk mechanisms between Kin and Ire1 signaling pathways.

TEACHING INTERESTS

My teaching interests are conjoined with my research interest in Molecular Genetics, both basic- and advance-level courses.I have been teaching the following courses:

Undergraduate level courses:

Discovering DNA: Our Society and Health, Bio Sci-103 (3 credits course)

Undergraduate Seminar in Microbiology: BioSci-671

Graduate level courses:

RNA Structure, Function & Metabolism: Bio Sci -597 (3 credits course)

Graduate seminar – Molecular & Cell Biology Bio Sci -975 (2 credits course)

Molecular Microbiology/Immunology: Bio Sci -725 (3 credits course)

Selected Publications

  1. Anshu, A, Mannan, M. A., Chakraborty, A., Chakrabarti, S and Dey, M. (2014). A Novel Role for Protein Kinase Kin2 in Regulating HAC1 mRNA Translocation, Splicing and Translation. Molecular and Cellular Biology (in press)
  2. Dey M.,Mann. B. R. Anshu, A., Mannan, M. A.(2014). Activation of Protein Kinase PKR Requires Dimerization-induced cis-Phosphorylation within the Activation Loop.Journal Biological Chemistry 289, 5747-5757.
  3. Mannan, M. A.Shadrick, W.R., Biener, G., Anshu, A., Raicu, V., Frick, D.N. and Dey, M. (2013). An ire1-phk1 chimera reveals a dispensable role of autokinase activity in endoplasmic reticulum stress response. Journal of Molecular Biology 425, 2083-99. A featured article ON JOURNAL FRONT COVER.
  4. Dey, M., Velyvis, A., Li, J., Chiu, E., Chiovitti, D., Kay, L., Sicheri, F., Dever, T. E. (2011). Requirement for kinase-induced conformational change in eIF2a restricts phosphorylation of Ser-51 Proceedings of the National Academy of Sciences,USA, 108 (11), 4316-21.
  5. Lee, K. P. K., Dey, M, Dante, N., Cao, C., Dever, T. E., Sicheri, F. (2008). Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell 132, 89-100.
  6. Dey, M., Cao, C., Sicheri, F., and Dever, T. E. (2007). Conserved salt-bridge interactions required for activation of protein kinases PKR, GCN2 and PERK. Journal Biological Chemistry 282, 6653-6660.
  7. Dey, M., Cao, C., Dar, A., Tamura, T., Ozato, K., Sicheri, F., and Dever, T. E. (2005).Mechanistic link between protein kinase PKR catalytic domain dimerization, autophosphorylation and eIF2a phosphorylation. Cell 122, 901-913.
  8. Dey, M., Trieselmann, B., Locke, E. G., Lu, J., Cao, C., Dar, A., Krishnamurthy, T., Dong, J., Sicheri, F., and Dever, T. E. (2005). PKR and GCN2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor eIF2B recognize overlapping surfaces on translation factor eIF2a. Molecular and Cellular Biology 25, 3063-75.
  9. Dey, M., and Guha-Mukherjee, S. (2000). Aspartate metabolism in Cicer immature seeds requires Ca2+, protein phosphorylation and dephosphorylation. Plant Science 150, 85-91.
  10. Dey, M., and Guha-Mukherjee, S. (1999). Phytochrome activation of aspartate kinase in etiolated chickpea (Cicer arietinum) seedling. Journal of Plant Physiology 154, 454-458