Shikha Singh Chauhan

Research Overview

The Chauhan laboratory is dedicated to understanding how the alteration of signaling networks leads to human disease and applying this knowledge to develop novel therapeutic strategies. We are an interdisciplinary group focused on investigating 2’,3’-cyclic nucleotide monophosphate (2’,3’-cNMPs) signaling across all three domains of life. The 2’,3’-cNMP-based stress response presents a novel and intriguing area of research, as the production, degradation, or sensing of these small cellular molecules remains poorly understood. Our goal is to study the production and regulation of 2’,3’-cNMPs in cells to uncover new pharmacological targets and pathways. Ultimately, we aim to utilize medicinal chemistry methods to develop novel small molecules targeting these pathways, with the goal of developing new antimicrobial and anticancer drugs.

Developing 2’,3’-cNMPs as novel antibiotics targeting bacterial translation

The well-established 3′,5′-cNMP signaling system has been a focal point of medicinal chemistry research, unlike the relatively unexplored 2′,3′-cNMP signaling. This is largely due to the limited understanding of its regulation and effector systems, creating a notable gap in our knowledge. However, recent research has provided insights into the effects of 2′,3′-cNMPs on physiological processes in bacteria. The study reveals that 2′,3′-cNMPs specifically bind to bacterial ribosomes and inhibit translation in vitro at concentrations observed in amino acid-starved E. coli cells. These findings offer valuable insights into the impact of 2′,3′-cNMP nucleotide signals on bacterial physiology and introduce new opportunities for developing novel antibiotics that target bacterial translation. Consequently, based on this work, our lab aims to design and synthesize novel 2’,3’-cNMP-based molecules as antibacterial agents capable of inhibiting translation in bacteria.

Investigating the therapeutic potential of targeting 2’,3’-cNMP signaling in Cancer

Investigating 2’,3’-cNMP signaling mechanisms associated with cancer cell malignancy may reveal new pharmacological targets. Although extensive research has been conducted on 3’,5’- cNMPs in various cancers, the role of 2’,3’-cNMPs in cancer cells has not been thoroughly explored, creating a significant knowledge gap and an opportunity for new discoveries. Several reports indicate the involvement of the 2’,3’-cAMP-adenosine pathway in cellular injuries and stress, suggesting its potential significance in uncontrolled proliferation and cancer. As a result, our laboratory is dedicated to elucidating the role of 2’,3’-cNMPs in cancer cells, representing a pivotal aspect of drug development. Our goal is to develop new chemical biology tools to study the regulation of 2’,3’-cNMPs in cancer cells and develop small molecules that target these regulatory pathways to develop novel anticancer agents.

Unveiling the impact of Archaeal cyclic nucleotide signaling on human health

The current understanding of nucleotide-based second messenger signal transduction in the archaeal domain is rudimentary. However, there is substantial evidence suggesting that Archaea may be involved in various infectious diseases in both humans and animals. Most of the archaea found in humans are methanogenic, known as methanogens, and their link to human infections has been attributed to methane production. Our lab is investigating the physiological roles and signaling pathways of cyclic nucleotide monophosphates found in archaea. By comprehending the function of cyclic nucleotide monophosphates in the growth and methanogenesis of archaea, we hope to gain new insights into their potential role in human diseases.