Anurag Tandon

Research Synopsis

The main focus of Dr. Tandon’s research is to understand the early events that lead to neurodegeneration in Parkinson’s disease and other progressive neurodegenerative disorders using cell and molecular biology techniques. α-Synuclein (α-syn) is a key pathogenetic factor involved in both inherited and sporadic forms of PD, as well as other neurodegenerative diseases. One of the consistent biochemical features of these diseases is a change in α-syn solubility, and our work aims to determine how its membrane binding is regulated and with which other proteins it interacts. We believe that both of these aspects modulate its solubility and are critical to uncovering its pathogenic role and its prion-like ability to propagate between connected neurons. Importantly, the underlying mechanism may be amenable to experimental manipulation as a means of influencing α-syn solubility in vivo so as to prevent its pathogenic accumulation. We are characterizing the role of cytosolic and extracellular proteins in regulating α-syn membrane attachment and have recently identified several novel a-syn-binding proteins that provide important clues as to how modifications to α-syn affect the survival of specific neurons. 

Additional projects in the laboratory involve the development of better cell and animal models which reflect pathogenic changes in PD, including alterations in the ubiquitin-proteasome degradation pathway, and the characterization of newer PD genes such as PINK1 and DJ-1.