Center for Gene Regulation in Health and Disease (GRHD)

Junior Gonzales

The Gonzales lab points towards the use/validation of re-engineered bio-tropical peptides to target ions channels, including sodium channels NaV1.7 and NaV1.8. It appears that these venom derived peptides are ideal vectors to deliver multiplex porphyrin/sensors to the peripheral nervous system where NaV1.7 is highly expressed.

For our research and for this purpose, we combine activities and techniques such as, dye synthesis, peptide modification(s), animal models, nuclear imaging, and NaV1.7 and NaV1.8 immunohistochemical staining. Taken all these techniques and tools, we aim to address urgent and unmet medical dysfunction including, cancer, neuropathies and tropical diseases.

1. “New Aporphinoid 5-HT2A and α1A Antagonists via Structural Manipulations of Nantenine.” Chaudhary, S., Ponnala, S., LeGendre, O., Gonzales, J. A., Navarro, H. A., Harding, W. W. Bioorg Med Chem, 2011, 19, (19), 5861-8, PMID: 21900013.

2. “Evaluation of structural effects on 5-HT2A receptor antagonism by aporphines: identification of a new aporphine with 5-HT2A antagonist activity.” Ponnala, S., Gonzales, J. A., Kapadia, N., Navarro, H. A., Harding, W. W. Bioorg Med Chem, 2014, 24, (07), 1664-7, PMID: 24630561.

3. “Facile synthesis of chlorin bioconjugates by a series of click reactions.” Gonzales, J., Bhupathiraju, N. V., Perea, W., Chu, H., Berisha, N., Bueno, V., Dodic, N., Rozenberg, J., Greenbaum, N. L., Drain, C. M., Chem Commun (Camb), 2017, 53(26): 3773-3776, PMID: 28304032.

4. “One-pot synthesis of four chlorin derivatives by a divergent ylide.” Gonzales, J., Bhupathiraju, N. V. S. D. K., Hart, D., Yuen, M., Sifuentes M. P., Maranan, M., Berisha, N., Batteas, J., Drain, M. C. J Org. Chem., 2018, 83 (12): 6307-6314, PMID: 29775305.

5. “Nanoemulsion-Based Delivery of Fluorescent PARP inhibitors in mouse model of small cell lung cancer.” Gonzales, J., Kossatz, S., Roberts, S., Pirovano, G., Brand, C., Perez-Medina, C., de la Cruz, M. J., Mulder, W. J. M., Reiner, T. Bioconjug Chem, 2018. 29(11): 3776-3782, PMID: 30354077.

6. “Fluorescence Imaging of Peripheral Nerves by a NaV1.7-targeted Inhibitor Cystine Knot Peptide.” Gonzales, J., Demetrio de Souza, P., Jiang, Y., Pirovano, G., Kossatz, S., Guru, N., Yarilin, D., Agwa, A., Schroeder, C., Patel, S., Ganly, I., King, G., Reiner, T. Bioconjug Chem, 2019. 30(11): 2879-2888, PMID:31647222.

7. “Fluorescent Labeling of a Nav1.7-Targeted peptide for near-infrared nerve visualization.” Gonzales, J., Pirovano, G., Demetrio de Souza, P., Chow, J., Kossatz, S., Guru, N., King, G., Lewis, J., Reiner, T. EJNMMI Research, 2020, 10(1): 49, PMID: 32409881.

8. “Leveraging synthetic chlorins for bio-imaging application.” Hernandez-Gil, J., Lewis, J. S., Reiner, T., Drain, C. M., Gonzales, J. Chem Commun (Camb), 2020, 56, 12608-12611, PMID: 32945820.

9. “Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers.” Gonzales, J., Hernandez-Gil, J., Wilson, T., Cornejo, M., Demetrio de Souza, P., Guru, N., Schroeder, C., King, G., Lewis, J., Reiner, T. Mol. Pharmaceutics, 2021, 18, 3, 940-951, PMID: 33404254.

10. “Pharmacological inhibition of the voltage-gated sodium channel NaV1.7 alleviates chronic visceral pain in a rodent model of irritable bowel syndrome.” Jiang, Y., Castro, J., Agwa, A., Blomster, L., Agwa, A., Maddern, J., Schober, G., Herzig, V., Chow, C., Cardoso. F., Demetrio, P., Gonzales, J., Schroeder, C., Esche, S., Reiner, T., Brierley, S., King, G. ACS Pharmacol. Transl. Sci., 2021, 4, 4, 1362-1378, PMID: 34423271.

11. “Non-invasive Imaging of Sense of Smell by Tracking the Voltage-Gated Sodium Channel NaV1.7.” Adilbay, D., Gonzales, J., M., Demetrio de Souza, P., Patel, S., Viray, T., Chow, C. Y., King, G., Pillarsetty, N., Reiner, T. bioRxiv, 2021, doi: https://doi.org/10.1101/2021.10.07.463532.

12. “Inhibition of microtubule dynamics in aggressive cancer cells by indole-modified latonduine derivatives and their metal complex.” Wittmann, C., Sivchenko, A., Bacher, F., Tong, K., Guru, N., Wilson, T., Gonzales, J., Rauch, H., Kossatz, S., Reiner, T., Babak, M., Arion, V. Inorg. Chem., 2022, 61, 3, 1456-1470, PMID: 34995063.