Ritika Gautam Singh
IIT Kanpur
Ritika Gautam Singh received her B.Sc.(Hons) and M.Sc. degrees in Chemistry from Banaras Hindu University and the Indian Institute of Technology Delhi, respectively. In 2012, she relocated to the United States to pursue doctoral studies at the University of Arizona. After receiving her PhD in Chemistry in August 2017, Ritika joined as a research associate at The Scripps Research Institute (TSRI), La Jolla, California. In the fall of 2019, Ritika returned to India to establish her independent research group at IIT Kanpur. Her group focuses on engineering metal-based diagnostics and therapeutics at the interface of biological inorganic chemistry, synthetic immunotherapy, and medicinal chemistry. Ritika has received notable early-career recognitions, including being named a ChemComm Royal Society of Chemistry Emerging Investigator and an American Chemical Society Organic & Inorganic Au Rising Star in 2023. She has successfully secured initial grants, including the DST INSPIRE Faculty Fellowship, SERB-SRG, CSIR ASPIRE, DST-AMR-TDP, and ICMR grants. In 2024, Ritika was inducted as an associate of the Indian Academy of Sciences, Bengaluru, marking another significant milestone in her growing career.
Session 1C: Inaugural Lectures by Fellows/Associates
A Jayakrishnan
Theragnostic and non-apoptotic paradigms in cancer therapy: From immunogenic ferroptosis therapy to dynamin-mediated cell death
Addressing therapeutic resistance in both immune-evasive and apoptosis-resistant tumors demands innovative strategies that combine selective cytotoxicity with diagnostic capabilities. In this context, we report two mechanistically distinct, yet complementary platforms based on metal-organic and organic nanoaggregates.<br /><br /> The first system involves a series of redox-active iron(III) complexes, [Fe(L1–L5)$_2$], derived from adamantyl-substituted sirtinol analogs. These complexes spontaneously form nanoscale aggregates in biological media (~50–70 nm) and effectively penetrate cancer cells through energy-dependent endocytosis. The lead compound, Fe(L1)₂, demonstrates hallmark features of immunogenic cell death (ICD), including CRT exposure, ATP release, and HMGB1 secretion, thereby “heating up” cold tumors and stimulating antitumor immunity. Notably, Fe(L1–L3)$_2$ also exhibit strong NIR-II photoacoustic signals, marking them as potential theragnostic agents for simultaneous deep-tissue imaging and immune reprogramming.<br /><br /> Complementing this, we developed a novel class of delocalized lipophilic cationic (DLC) compounds that self-assemble into nanoaggregates and trigger a unique dynamin-dependent, non-apoptotic cell death in A549 lung adenocarcinoma cells. The lead molecule, L3, induces massive cytoplasmic vacuolization, mitochondrial dysfunction, and ATP depletion. It disrupts mitochondrial membrane potential, promotes mitochondrial permeability transition pore (MPTP) opening, and disturbs glutathione-mediated redox homeostasis. This mechanism of action is particularly promising against apoptosis-resistant tumors and impairs both metastasis and clonal expansion.<br /><br /> Together, these studies offer two robust platforms—one that integrates immune activation and imaging, and another that bypasses classical apoptotic resistance—paving new avenues for treating refractory cancers through multifunctional nanoaggregate-based therapeutic.