Cellular homeostasis, signal transduction, and intercellular communication depend critically on the structural and chemical integrity of lipid membranes. However, reactive stress mediators generated during oxidative and nitrative stress can disrupt membrane organization, leading to cell death and tissue injury. To directly visualize membrane-localized stress, we developed fluorogenic lipidoids that report on redox activity within lipid environments [1,2]. These probes were derived from phosphoglycerolipids incorporating redox-responsive fluorogens within their headgroups. Experimental studies confirmed selective membrane localization and redox sensing at the membrane interface without perturbing bilayer organization. Furthermore, our peroxynitrite-responsive lipidoid enabled the direct detection of nitrative stress in both ex vivo precision-cut lung slices and in vivo murine models of acute lung injury.
In parallel, we developed nucleic acid-based sensors (aptasensors) to detect disease biomarkers and reactive redox species [3,4]. Bacteria, notably Escherichia coli, provide a convenient and robust platform for constructing whole-cell biosensors. We successfully implemented a genetically encodable aptasensor system in E. coli, thereby transforming the bacteria into cell-based redox sensors without alteration of endogenous signaling pathways [4]. We are expanding these nucleic acid-based molecular tools to exploit catalysis for modulating gene expression as the next-generation cancer therapeutics.
Finally, our laboratory leads a multifaceted research program at the interface of immune signaling and medicinal chemistry. Immune signaling is central to host defense, inflammation, and cancer immunotherapy. Because signaling outcomes depend on the precise timing and localization of signaling proteins, these pathways must be tightly regulated. While transient pathway activation is essential for host defense, persistent signaling can drive chronic inflammation, contributing to autoinflammatory disease while promoting tumor progression [5]. We are developing molecular probes that enable direct imaging of endogenous signaling proteins and real-time measurement of immune activation in living cells. These probes support both confocal and super-resolution imaging at nanomolar probe concentrations, providing high sensitivity with minimal background labeling. Our technology enables direct visualization of endogenous protein localization and dynamic distribution during immune signaling, providing mechanistic insights and guiding the development of potent, targeted therapies.
References
[1] Gutierrez, B.; Aggarwal, T.; Erguven, H.; Stone, M. R. L.; Guo, C.; Bellomo, A.; Abramova, E.; Stevenson, E. R.; Laskin, D. L.; Gow, A. J.; Izgu, E. C.* iScience 2023, 26 (12), 108567.
[2] Erguven, H.; Wang, L.; Gutierrez, B.; Beaven, A. H.; Sodt, A. J.; Izgu, E. C.* JACS Au 2024, 4 (5), 1841–1853.
[3] Wang, L.; Hast, K.; Aggarwal, T.; Baci, M.; Hong, J.; Izgu, E. C.* Bioorg. Med. Chem. 2022, 69, 116909.
[4] Aggarwal, T.; Wang, L.; Gutierrez, B.; Guven, H.; Erguven, H.; Cho, S.; Izgu, E. C.* Angew. Chem. Int. Ed. 2025, 64 (12), e202421936.
[5] Joshi, A.; Izgu, E. C.* Drug Discov. Today 2026, 31 (3), 104646.
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Enver Cagri Izgu is an Associate Professor in the Chemistry and Chemical Biology Department at Rutgers University–New Brunswick. Dr. Izgu earned a Bachelor of Science degree in Chemistry from the Middle East Technical University in Turkiye, where he studied asymmetric organic catalysis with Dr. Ozdemir Dogan. Then he joined the Ph.D. program at the University of Minnesota, where he completed the total synthesis of a natural alkaloid product and developed methodologies for carbon-carbon bond formation under the tutelage of Dr. Thomas Hoye. Following graduate work, he conducted postdoctoral research with Dr. Jack Szostak at Harvard University, studying the biochemistry of genetic polymers and protocell models that harness oligonucleotides, peptides, and lipids.
The Izgu Laboratory at Rutgers University–New Brunswick leads an interdisciplinary research program focused on biosensing and biomedicine, integrating synthetic organic chemistry with cellular and molecular biology. Major efforts in his group focus on developing chemically engineered systems, including small molecules and biomacromolecules, to interrogate disease-associated processes and to modulate biological pathways toward precision medicine.
Dr. Izgu and his laboratory have received notable recognitions, including the Institutional Research Grant New Investigator Award from the American Cancer Society; the National Institutes of Health (NIH) Trailblazer Award from the National Institute of Biomedical Imaging and Bioengineering; the NIH Maximizing Investigators’ Research Award from the National Institute of General Medical Sciences; and Interstellar Initiative Early Career Investigator from the New York Academy of Sciences and Japan Agency for Medical Research and Development.
