Associate Professor Madhusudan Dey and Assistant Professor An Phu Tran Nguyen are the most recent additions to our group of MIDD members. Both researchers are members of the Department of Biological Science at the University of Wisconsin Milwaukee.

Professor Madhusudan Dey (right) is interested in understanding the fundamental mechanisms that regulate the initiation of protein synthesis (translation) and protein folding inside the endoplasmic reticulum (ER). 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 repressed HAC1 mRNA in yeast cells or XBP1 mRNA in human cells. The Dey lab studies how HAC1 mRNA is translationally repressed and how the ER stress de-represses HAC1 mRNA translation. The Dey lab is also working together with Prof Frost, Mirza and Troy to characterize new antibiotics that are isolated from Xenorhabdus szentirmaii.

Professor An Phu Tran Nguyen (left) studies the cellular and molecular mechanisms that underlie Parkinson’s disease (PD). His research has uncovered the significance of the gene responsible for encoding leucine-rich repeat kinase 2 (LRRK2, also known as PARK8). Mutations in LRRK2 are the most prevalent genetic anomalies observed in PD patients. LRRK2 is a dual enzyme protein, exhibiting both GTPase and kinase activities, rendering it an appealing target for potential PD therapies. The most common LRRK2 mutation, G2019S, resides in its kinase domain and results in an abnormal elevation in its kinase activity. Through the development of a rat model that overexpresses LRRK2 using recombinant human adenovirus serotype 5 (Ad5) as a gene transfer vector, we have demonstrated that G2019S LRRK2 triggers dopaminergic neuron death in the rat brain in a manner dependent on both its GTPase and kinase functions.