Laboratory of Chemical Biology and Neurochemistry

We are broadly interested in creating innovative chemical tools using small molecules, DNA devices, and polymer bio-conjugates for functional imaging and modulating biological systems. Leveraging these methods, we aim to understand complex biological phenomena and disease mechanisms at a molecular level, particularly in neurological disorders. With a strong foundation and interdisciplinary collaboration, we will contribute significantly to chemical neurobiology, bridging scientific inquiry and transformative healthcare.

Our interests span:

• Pioneering innovative bioconjugation techniques enable precise endogenous protein labeling and stable organellar staining, unveiling critical insights into the fundamental principles of organellar dynamics and neurotransmitter receptor trafficking. 
• Developing fluorogenic probes using novel targeting strategies and innovative quantitative principles for functional organelle imaging, aiming to deepen our understanding of organelle biochemistry. 
• Utilizing DNA nanotechnology and polymer bioconjugates to devise novel modulation strategies, we investigate the role of organellar microenvironments in facilitating diverse cellular processes such as viral infection, neurotransmitter filling and synapse formation.

Our research will commence with the synthesis of 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.

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)