Ishwar S. Singh, PhD

Scottish Church College, Kolkata, India    BSc   1979  Chemistry

University of Calcutta, Kolkata, India     MSc   1981   Biochemistry

University of Calcutta, Kolkata, India   PHD    1989   Biochemistry

The heat shock (HS) response is an ancient and highly conserved cellular response to stress. It is activated upon exposure to a myriad of stress including fever and febrile responses. The long-term goals of our group is to understand the molecular mechanisms by which the HS response interacts with innate immune responses to modify both processes, and the clinical consequences of these interactions on inflammation, host tissue injury, sepsis and shock.          

Our studies have identified fever as an important factor in the pathogenesis of infection, inflammation, and lung injury and showed that febrile-range hyperthermia (FRH; core temperature ~39.5°C) modified expression of several cytokine and chemokine genes and recruitment of transcription factors to gene-specific chromatin, modified programmed cell death in neutrophils and epithelial cells and modified the activation and recruitment of neutrophils to sites of infection, injury and inflammation. We have found that TLR agonists and interleukin (IL)-1β, which share the same MyD88-dependent signaling pathway and participate in driving inflammation in sepsis, ARDS and systemic inflammatory response syndrome (SIRS), interact with fever to augment the HS response and enhance the release of danger molecules, DAMPS and alarmins directly, via increased exosomal secretion and following cellular necrosis. Currently, we have been focusing on the role of the HS response pathway in the process of epithelial-mesenchymal transition (EMT). We have found evidence that components of the HS response pathway including the stress-activated transcription factor heat shock factor-1 (HSF1) and heat shock protein (HSP)-70 can modify the EMT process and regulating the HS response pathway can have therapeutic benefit.

Fever, heat acclimation, heat shock, HSF1, HSP70, TLR, TNF,

Hasday JD and Singh IS. (2000)  Fever and the stress response: Distinct, partially overlapping processes. Cell Stress Chaperones 5, 471-80.

Nagarsekar A, Hasday JD, Singh IS. (2005) CXC Chemokines: A new family of Heat-shock proteins? Immunol Invest. 34: 381-98.

Singh IS, Hasday JD. (2013) Fever, hyperthermia and the heat shock response. Int J Hyperthermia. 29: 423-35.

Hasday JD, Thompson C, Singh IS. (2014) Fever, immunity, and molecular adaptations. Compr Physiol. 4:109-48.