Research interests: We are primarily interested in understanding of chaperone machinery in the context of neurodegenerative diseases. The major focus is to gain insight into cellular factors that regulate chaperone function in either folding or degradation of Parkinson’s disease-associated proteins through processes such as autophagy.

Chaperone-mediated autophagy (CMA): Cellular proteins containing KFERQ-like motifs are translocated into lysosomes under stress. Cytosolic Hsp70 play a key role in the process by recognizing such substrates and translocating them to LAMP-2A receptor protein on lysosomes. We are exploring regulatory aspects of the role of Hsp70s in the CMA in neuronal cells.

RNAphagy: RNA translocates into lysosomes/vacuoles under stress. We are exploring various components of the cellular machinery that regulates this process.

Hsp70 interactome: Eukaryotes encode multiple cytosolic Hsp70s of which some are constitutive and others stress-inducible. Hsp70s interact with Hsp40s and nucleotide exchange factors (NEF). Similar to Hsp70s, there are multiple Hsp40s and NEFs. We are exploring whether specific Hsp70-Hsp40-NEF complexes are formed under different cellular conditions, and if formed what is the functional significance of such network.

The lab utilizes cellular models such as yeast and mammalian cells or animal models such as C. elegans and mouse models of Parkinson’s disease.

• Bajaj M., Muddassir M., Choi B., Singh P., Park J.B. , Singh S., Yadav M. Kumar R., Eom K., Sharma D. (Int J Biol Macromol. 2023) Single-molecule analysis of osmolyte-mediated nanomechanical unfolding behavior of a protein domain.
• Gaur D, Kumar N, Ghosh A, Singh P, Kumar P, Guleria J, Kaur S, Malik N, Saha S, Nystrom T, Sharma D (Plos Genetics, 2022), Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation.
• Puri A, Singh P, Kumar N, Kumar R, Sharma D. Tah1, a key component of R2TP complex that regulates assembly of snoRNP, is involved in de novo generation and maintenance of yeast prion [URE3]. J Mol Biol, 2021
• Kumar P, Sahoo D. K., Sharma D. The identification of novel promoters and terminators for protein expression and metabolic engineering applications in Kluyveromyces marxianus. Metab Eng Commun, 2021
• Gaur D, Singh P, Guleria J, Gupta A, Kaur S, Sharma D. The yeast Hsp70 co-chaperone Ydj1 regulates functional distinction of Ssa Hsp70s in the Hsp90 chaperoning pathway. Genetics, 2020

• Potent peptide inhibitors of protein aggregation- USA-16/647,149
• Novel peptide as potent inhibitor of protein aggregation (Japan-7210560)
• Potent peptide Inhibitors of protein aggregation (0121NF2017_EP)
• Recombinant vector for high-expression of proteins in yeasts (China-ZL202080060401.X, CN 114341358 B)