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Madhusudan Dey

  • Member, Milwaukee Institute for Drug Discovery (MIDD)

Professor of Biological Science

Education

  • PhD, Life Sciences, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India, 1994 - 2000
  • MSc, Biotechnology, School of Biotechnology, Madurai Kamaraj University, Tamil Nadu, India, 1992-1994

Research Interests

The Dey lab is interested in understanding the fundamental mechanisms that regulate the initiation of protein synthesis (translation) and that regulate the protein folding inside the endoplasmic reticulum (ER).

Translation is a process in which messenger RNA is decoded into a polypeptide chain. This process requires many trans-acting factors (e.g., eIF1, eIF2, eIF2B, eIF3, eIF4, eEF1, etc.) that interact with the ribosome, messenger RNA and transfer RNA. This process is controlled by many protein kinases, including PKR, PERK and GCN2. The Dey lab studies how PKR and PERK specifically phosphorylates eIF2 and how phosphorylated eIF2 inhibits the initiation of protein synthesis.

Almost 30% of nascent proteins co-translationally migrate to the ER, where they fold and mature into biologically active forms. Under patho-physiological conditions, the nascent proteins are unable to fold properly, resulting in accumulation of unfolded/mis-folded proteins inside the ER – a state termed “ER stress”. The ER stress activates cellular responses known as the unfolded protein response (UPR). The UPR involves three major sensors Ire1, PERK and ATF6 in mammalian species. In model organism yeast, only Ire1 senses and signals the UPR. Ire1 initiates the UPR signals by processing the translationally repressedHAC1mRNA in yeast cells orXBP1mRNA in human cells. The Dey lab studies howHAC1mRNA is translationally repressed and how the ER stress de-repressesHAC1mRNA translation.

Recently, the Dey lab has discovered that kinase Kin1 and its isoform Kin2 (mammalian homolog of microtubule affinity regulating kinase, MARK) play a novel regulatory role in the yeast UPR, in addition to their canonical role in cellular exocytosis. This discovery leads them to characterize the Kin-signaling pathway in the yeast UPR.

Selected Publications

George J, Li Y, Kadamberi IP, Parashar D, Tsaih SW, Gupta P, Geethadevi A, Chen C, Ghosh C, Sun Y, Mittal S, Ramchandran R, Rui H, Lopez-Berestein G, Rodriguez-Aguayo C, Leone G, Rader JS, Sood AK, Dey M, Pradeep S, Chaluvally-Raghavan P. Cell Rep. (2023), 42 (3), 112228.

Uppala, Jagadeesh K., Sathe, Leena, and Dey, Madhusudan.Journal of Biological Chemistry. (2022), 298 (3), 101648.

Dey, Madhusudan, and Uppala, Jagadeesh K. Bio-Protocol. (2022), 20 (4), e4331.
George, Jasmine, Dey, Madhusudan, and Chaluvally-Raghavan, Pradeep.Cell ReportsNov 2;37(5. (2021): 109934.
Ghosh, Chandrima, Uppala, Jagadeesh K., and Dey, Madhusudan. Science Signaling. (2021), 25 (14), eaaz4401.
Dey, Madhusudan, and Uppala, Jagadeesh.Molecular and Cellular Biology. (2021), 41 (7), e0066220.
Sathe, Leena, Bolinger, C, Mannan, MA, Dever, TE, and Dey, Madhusudan. J Biol Chem290. Ed. Dey, Madhusudan. (2015): 21821-32.
Anshu, A, Mannan, MA, Chakrabarty, A, Chakrabarti, S, and Dey, Madhusudan.Mol Cell Biol.35. Ed. D, Madhusudan. (2015): 199-210.
Dey, Madhusudan. “Activation of Protein Kinase PKR Requires Dimerization-induced cis-Phosphorylation within the Activation Loop.”Journal Biological Chemistry289. (2014): 5747-5757.
Mannan, M. Amin-ul, Shadrick, William R., Biener, Gabriel, Anshu, Ashish, Raicu, Valerica, Frick, David N., and Dey, Madhusudan.J. Mol. Biol.425. (2013): 2083-99.
Dey, Madhusudan. Proc. Natl. Acad. Sci. USA108.11 (2011): 4312-21.