Guest Editors
Dr. Nitika
University of North Carolina at Charlotte
Dr. Nitika is a Post-Doctoral Researcher in Dr. Andrew Truman’s lab. Her research interests involve determining how molecular chaperone function and how they can be manipulated in cancer. Her work focuses on identifying novel ways to manipulate Hsp70 function by either inhibiting specific “helper” co-chaperone proteins such as HDJ2 or chaperone post translational modifications (PTMs). She has demonstrated that the ribonucleotide reductase (RNR) complex, a key enzyme in DNA replication, requires the Hsp70 co-chaperone HDJ2 for activity. Furthermore, inhibition of HDJ2 using a small molecule inhibitor sensitizes cancer cells to RNR inhibitors such as hydroxyurea and triapine. She has identified novel synergistic anticancer drug combinations with HDJ2 inhibition using chemogenomic screens with the NIH Approved Oncology drug collection. These results confirm that HDJ2 is a hub for anticancer drug resistance and that HDJ2 inhibition is a potent strategy to sensitize cancer cells to current and future therapeutics. The large change in drug efficacy linked to HDJ2 suggests a personalized medicine approach where tumor HDJ2 status may be used to optimize therapeutic strategy.
Dr. Andrew W. Truman
University of North Carolina at Charlotte
Dr. Andrew W. Truman is a British-American Biochemist and Cancer Biologist. Dr. Truman completed postdoctoral studies at Johns Hopkins Bloomberg School of Public Health and at Boston University. He joined the laboratory of Dr. Stephen Kron at the University of Chicago as a Research Professional Associate in 2010. In 2015, he joined the Department of Biological Sciences at UNC Charlotte and in 2021 was promoted to Associate Professor with Tenure. He is a Senior Editor for the journal Cell Stress and Chaperones and a Review Editor for Frontiers in Molecular Biosciences. He became a fellow of the Cell Stress Society International (FSSI) in 2020. Dr. Truman is recognized for his research on the interplay of molecular chaperones and signal transduction pathways. In particular, he has been a major proponent of the idea of the “Chaperone Code”, the combination of post-translational modifications that regulate chaperone function. Dr. Truman’s laboratory has discovered a reliance of the important ribonucleotide reductase complex on molecular chaperones. This work has led to other studies examining synergy between drugs that inhibit RNR and chaperones in cancer. His research team has been supported by grants from the National Institute of General Medical Sciences and National Cancer Institute to explore the connection between chaperones and the cellular response to DNA damage.
Collection Overview
Molecular chaperones belong to the heat shock protein (Hsp) family including Hsp70, Hsp90, and Hsp40s. Molecular chaperones are involved in many critical cellular processes including folding of proteins, modulation of protein-protein interactions, and transport of proteins across the membrane. Due to a large number of proteins (clients) that require them for function, Hsps are essential for cell viability and are implicated in a variety of diseases. Hsps are highly expressed in many cancers and neurodegenerative diseases. Cancer cells are dependent on Hsps for their survival because they need to cope up with factors such as nutrient deprivation and hypoxia. Molecular chaperones are associated with the accumulation of these toxic misfolded protein species in neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Thus, molecular chaperone inhibition is an area of active research for various diseases with emerging new chaperone inhibitors.
In this collection, we intend to share protocols for techniques used for molecular chaperone inhibition and open networks for new collaborations for the chaperone field.
