Laboratory of Chemical Biology and Neurochemistry

Our research is centered on the molecular design and synthesis of innovative chemical tools, particularly small-molecule fluorescent probes, for functional imaging and modulation of biological systems. We integrate principles of synthetic organic chemistry, photophysics, and supramolecular chemistry to develop responsive probes with high spatial and temporal precision. Using these chemical platforms, we seek to interrogate complex biological processes and disease mechanisms at the molecular level, with a particular emphasis on neurological disorders. Through an interdisciplinary approach, our work aims to advance chemical biology while bridging fundamental chemistry with translational applications in healthcare.

Our interests span:

• Design and synthesis of small-molecule fluorescent probes for precise targeting and imaging of subcellular organelles.
• Development of quantitative imaging tools to monitor ion dynamics, neurotransmitters, and enzyme activities within organelles, enabling deeper insights into organelle-specific biochemistry.
• Application of chemical probes in disease models, particularly neurodegenerative disorders, to elucidate the role of organelle dysfunction in disease onset and progression.
• Engineering light-responsive (photoactivatable) chemical systems to modulate organelle microenvironments, facilitating spatiotemporal control of cellular processes and exploring their therapeutic potential.

Our research will commence with the the rational design and synthesis of small molecule based fluorescent probes, followed by their characterization using various spectroscopic techniques. We will then explore these probes in both cell lines and primary cells, and conduct functional imaging with high-resolution fluorescence microscopy.

24. Optimised Strategies for Exploring Organelle Ion Dynamics. P. Anees. ChemBioChem., 26, e202500557 (2025) https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cbic.202500557

23. Distinguishing the Bimodal Interaction of a Squaraine Dye with a Protein by a Functional Group Photodeprotection Strategy. P. Anees. G. Saranya, S. Sreejith, A. Ajayaghosh. Chem Asian J., 20, e202401517 (2025) 

22. Quantitative chemical imaging of organelles. P. Anees^†, J. Tinker^†, Y. Krishnan. Acc. Chem. Res., 57, 1906-1917 (2024) https://pubs.acs.org/doi/full/10.1021/acs.accounts.4c00191

21. A mechanism of lysosomal calcium entry M. Zajac, P. Anees^†, S. Mukherjee^†, D. Oettinger, K. Henn, J. Srikumar, J. Zou, A. Saminathan, Y. Krishnan. Sci. Adv., 10, eadk2317 (2024) (https://www.science.org/doi/abs/10.1126/sciadv.adk2317)

20. Detecting organelle-specific activity of potassium channels with a DNA nanodevice. P. Anees, A. Saminathan, E. R. Rozmus, D. Anke, A. B. Malik, B. P. Delisle, Y. Krishnan. Nat. Biotechnol. 2024 (https://doi.org/10.1038/s41587-023-01928-z)

19. A DNA nanodevice for mapping sodium at single organelle resolution.  J. Zou, K. Mitra, P. Anees, D. Oettinger, J. Ramirez, A. T. Veetil, P. D. Gupta, R. Rao, J. J. Smith, P. Kratsios, Y. Krishnan. Nat. Biotechnol. 2024 (https://doi.org/10.1038/s41587-023-01950-1)

18. Passive endocytosis in model protocells. S. J. Zhang, L. A. Lowe, P. Anees, Y. Krishnan, T. G. Fai, J. W. Szostak, A. Wang. PNAS 2023 120, 2221064120. (https://www.pnas.org/doi/full/10.1073/pnas.2221064120)  

17. Plasma membrane depolarization reveals endosomal escape incapacity of cell-penetrating peptides. M. Serulla, P. Anees, A. Hallaj, E. Trofimenko, T. Kalia, Y. Krishnan, C. Widmann. Eur. J. Pharm. Biopharm. 2023, 184, 116–124. (https://www.sciencedirect.com/science/article/pii/S093964112300019X)

16. Achieving Organelle-level Precision with Next-Generation Targeting Technologies. A. Saminathan^†, M. Zajac^†, P. Anees, Y. Krishnan. Nat. Rev. Mater., 2022, 7, 355-371. (https://www.nature.com/articles/s41578-021-00396-8)

15. Tissue-Specific Targeting of DNA Nanodevices in a Multicellular Living Organism. K. Chakraborty, P. Anees, S. Surana, S. Martin, J. Aburas, S. Moutel, F. Perez, S. P. Koushika, P. Kratsios, Y. Krishnan. Elife 10, e67830, 2021. (https://elifesciences.org/articles/67830)

14. Quantifying phagosomal HOCl at single immune-cell resolution. P. Anees, M. Zajac, Y. Krishnan. Methods in Cell Biology 164, 119-136 (2020). (https://www.sciencedirect.com/science/article/abs/pii/S0091679X20301898)

13. Surface vs. Core N/S/Se-Heteroatom Doping of Carbon Nanodots Produces Divergent Yet Consistent Optical Responses to Reactive Oxygen Species. X. Geng, T. R. Congdon, P. Anees, A. A. Greschner, F. Vetrone, M. A. Gauthier. Nanoscale Adv., 2020, 2, 4024-4033. (https://pubs.rsc.org/en/content/articlehtml/2020/na/d0na00439a)

12. Homogenous Scavenging Resolves Low-Purification Yield/Selectivity Caused by Secondary Binding of Protein-A to Antigen-Binding Antibody Fragments. P. Anees, M. A. Gauthier. Biomacromolecules 2020, 21, 825–829. (https://pubs.acs.org/doi/abs/10.1021/acs.biomac.9b01516)

11. Evidence, Manipulation, and Termination of pH ‘Nanobuffering’for Quantitative Homogenous Scavenging of Monoclonal Antibodies. P. Anees, Y. Zhao, A. A. Greschner, T. R. Congdon, H. W. de Haan, N. Cottyne, M. A. Gauthier. ACS Nano 2019, 13, 1019–1028. (https://pubs.acs.org/doi/full/10.1021/acsnano.8b07202)

10. A Ratiometric Near-Infrared Fluorogen for the Real Time Visualization of Intracellular Redox Status during Apoptosis. G. Saranya, P. Anees, M. M. Joseph, K. K. Maiti, A. Ajayaghosh. Chem. Eur. J., 2017, 23, 7191–7195. (https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.201700839)

9. A Three-Photon Active Organic Fluorophore for Deep Tissue Ratiometric Imaging of Intracellular Divalent Zinc. D. S. Philips, S. Sreejith, T. He, N. V. Menon, P. Anees, J. Mathew, S. Sajikumar, Y. Kang, M. C. Stuparu, H. Sun, Y. Zhao, A. Ajayaghosh. Chem. Asian J., 2016, 11, 1523–1527. (https://onlinelibrary.wiley.com/doi/abs/10.1002/asia.201600170)

8. Self-assembly in sensor nanotechnology. P. Anees, V. K. Praveen, K. K. Kartha, A. Ajayaghosh. Comprehensive Supramolecular Chemistry II, for Volume 9 (2016), Elsevier Ltd, UK. (https://cir.nii.ac.jp/crid/1364233270233069184)

7. A Protein-Dye Hybrid System as Narrow Range Tunable Intracellular pH Sensor. P. Anees, K. V. Sudheesh, P. Jayamurthy, A. R. Chandrika, R. V. Omkumar, A. Ajayaghosh. Chem. Sci., 2016, 7, 6808−6814. (https://pubs.rsc.org/en/content/articlehtml/2016/sc/c6sc02659a) 

6. Real Time Monitoring of Aminothiol Level in Blood Using a Near-Infrared Dye Assisted Deep Tissue Fluorescence and Photoacoustic Bimodal Imaging. P. Anees, J. Joseph, S. Sreejith, N. V. Menon, S. W. K. Yu, Y. Kang, A. Ajayaghosh, Y. Zhao. Chem. Sci., 2016, 7, 4110−4116. (https://pubs.rsc.org/en/content/articlehtml/2016/sc/c5sc04986e)

5. A squaraine based fluorescent probe and a process for the preparation thereof. P. Anees, A. Ajayaghosh, (2017) US patent, US9791451B2 (https://patents.google.com/patent/US9791451B2/en)

4. Near-IR Squaraine Dye–Loaded Gated Periodic Mesoporous Organosilica for Photo-Oxidation of Phenol in a Continuous-Flow Device. P. Anees, P. Borah, S. Sreejith, N. V. Menon, Y. Kang, A. Ajayaghosh, Y. Zhao. Sci. Adv.,2015;1:e1500390. (https://www.science.org/doi/abs/10.1126/sciadv.1500390)

3. Self-assembled Near-Infrared Dye Nanoparticles as a Selective Protein Sensor by Activation of a Dormant Fluorophore. P. Anees, S. Sreejith, A. Ajayaghosh. J. Am. Chem. Soc., 2014, 136, 13233−13239. (https://pubs.acs.org/doi/full/10.1021/ja503850b)

2. Heteroaromatic Donors in Donor–Acceptor–Donor Based Fluorophores Facilitate Zinc Ion Sensing and Cell Imaging. S. Sreejith, K. P. Divya, P. Jayamurthy, J. Mathew, V. N. Anupama, D. S. Philips, P. Anees, A. Ajayaghosh. Photochem. Photobiol. Sci., 2012, 11, 1715–1723. (https://pubs.rsc.org/en/content/articlelanding/2012/pp/c2pp25110h/unauth)

1. A Zn²⁺-Specific Fluorescent Molecular Probe for the Selective Detection of Endogenous Cyanide in Biorelevant Samples. K. P. Divya, S. Sreejith, B. Balakrishna, P. Jayamurthy, P. Anees, A. Ajayaghosh.  Chem. Commun., 2010, 46, 6069–6071. (https://pubs.rsc.org/en/content/articlehtml/2010/cc/c0cc01159b)