A. Females are twice as prone to experiencing anxiety and depression as males and earlier studies have indicated that the neurotransmitter serotonin 5-HT is involved in this process. Our studies have revealed that female mice are selectively dependent on serotonin 1A receptor (5-HT1A-R) mediated signaling for normal anxiety behavior. A deficiency of this receptor and the consequent aberrant development of some hippocampal neurons could be associated with this female-specific anxiety in adulthood. Our current studies are focused on understanding the possible role of sex steroids in cooperative signaling with the 5-HT1A-R and if such signaling activities are linked to the female-specific anxiety disorders.
B. Using the Fmr1 knockout (FXS) mouse model for autism, we have demonstrated aberrant AMPA receptor translocation to the plasma membrane in the hippocampal neurons of early postnatal FXS mice. A selective activator of PKC, which normalizes anxiety behavior in other mouse models was able to normalize AMPA receptor translocation as well as anxiety and social behavior in the FXS mice. The PKC gene is a known substrate for the RNA-binding protein Fmr1. This project will build a mechanistic understanding of the role of Fmr1 and PKC in neonatal hippocampal development, AMPA receptor transport, brain inflammation, and adult behavior linked to autism.
C. Curcumin (CC), a component of the culinary spice turmeric, displays prophylactic activity against almost all cancers, but, due to its poor bioavailability, it is ineffective in eliminating established tumors. We have used a hydrolysable ester bond to link CC to a targeting antibody (Ab) against the antigen CD68, which is highly expressed by glioblastoma cells derived from a large number of patients. Upon endocytosis of the CD68Ab-CC adduct, free CC is released by intracellular esterases, thereby killing the GBM cells. The tumoricidal activity of the CD68Ab-CC adduct is 2 to 3 orders of magnitude higher than that of free CC. We have discovered that CC also repolarizes tumor-associated microglia and macrophages from the tumor-promoting M2 phenotype to the tumoricidal M1 state. Currently, we are testing a number of delivery strategies to translate our technology to the clinical setting.
Patents:
i) “Novel Curcumin-antibody Conjugates as Anti-Cancer Agents”. Banerjee, P. and Raja, K. 1038-58 PCT/US/Approved 2016 (approved).
ii) “Novel Curcumin and Tetrahydrocurcumin derivatives”. Raja, K. (PI) and Banerjee, P. PCT Canada/ 2012/07A0020. (approved).
Degrees
M.Sc., Jadavpur University, Calcutta, India
Ph.D., Indian Institute of Science, Bangalore, India
Post-doc training:Joseph Kennedy Mental Retardation Center, Department of Pediatrics, University of Chicago Hospital
Publications (selected from 87):
1. Mukherjee, S., Fried, A., Hussaini, R., White, R., Baidoo, J., Yalamanchi, S., and Banerjee, P. (2018) Journal of Experimental & Clinical Cancer Research, 37, 168. Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophage and elimination of GBM and GBM stem cells.
2. Mukherjee, S., Hussaini, R., White, R., Atwi, D., Fried, A., Sampat, S., Piao, L., Pan, Q., and Banerjee, P. (2018) Cancer Immunology, Immunotherapy, 67, 781-774. TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.
3. Mukherjee, S., Baidoo, J., Sampat, S., Mancuso, A., David, L., Cohen, L.S., Zhou, S., Banerjee, P. (2018) Molecules, 23, 201. Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells.
4. Wang, H., Mukherjee, S., Yi, J., Banerjee, P., Chen, Q., and Zhou, S. (2017) ACS Applied Materials & Interfaces. Biocompatible chitosan-carbon dots hybrid nanogels for NIR imaging-guided synergistic photothermal/chemo-therapy. 9, 18639-18649.
5. Punia, K., Punia, A., Chatterjee, K., Mukherjee, S., Fata, J., Banerjee, P., Raja, K., and Yang, N.L. (2017) Rapid bactericidal activity of amphiphilic polyacrylate terpolymer system comprised of same centered comonomers with 2-carbon and 6-carbon spacer arms and an uncharged repeat unit. RSC Advances, 7, 10192-10199.
6. Mukherjee, S., Debata, P.R., Hussaini, R., Chatterjee, K., Baidoo, J.N.E., Sampat, S., Navarra, J.P., Fata, J., Severinova, E., Banerjee, P.*, and Castellanos, M.R. (2017) Oncotarget, 8, 60904-60916. Unique synergistic formulation of curcumin, epicatechin gallate and resveratrol, TriCurin, suppresses HPV E6, eliminates HPV+ cancer cells, and inhibits tumor progression. *Corresponding author.
7. Mukherjee, S., Baidoo, J., Fried, A., Atwi, D., Dolai, S., Boockvar, J., Symons, M., Ruggieri, R., Raja, K., and Banerjee, P. (2016) International Journal of Cancer, 139, 2838-2849. Curcumin changes the polarity of tumor-associated microglia and eliminates glioblastoma.
8. Kerr, D.J., Marsillo, A., Guariglia, S.R., Budylin, T., Sadek, R., Menkes, S., Chauhan, A., Wen, G.Y., McCloskey, D.P., Wieraszko, A., and Banerjee, P. (2016) BBA - Molecular Basis of Disease, 1862, 1755-1765. Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity and autistic-like behavior.
9. Samaddar, S., Schroder, R., and Banerjee, P. (2015) BAOJ Neuro 1: 005. Rectification of Aberrant Mossy Fiber connections by DCP-LA, Selective Activator of PKC Epsilon: A Possible Target for Later-Life Mood Disorders.
10. Samaddar, S., Ranasinghe, B., Tantry, S.J., Debata, P.R., and Banerjee, P. (2015) Adv Exp. Med. Biol., 842, 375-388. Involvement of Vascular Endothelial Growth Factor in Serotonin 1A Receptor-Mediated Neuroproliferation in Neonatal Mouse Hippcampus.
11. Butt, I., Hong, A., Di, J., Aracena, S., Banerjee, P., and Shen, C.-H. (2014) Neuropeptides, 48, 313-318. The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor.
12. Langone, P., Debata, P.R., Inigo, J.D.R., Dolai, S., Mukherjee, S., Halat, P., Mastroianni, K., Curcio, G.M., Castellanos, M.R., Raja, K., and Banerjee, P. (2014) Int. J. Cancer, 135, 710-719. Coupling to a Glioblastoma-directed Antibody Potentiates Anti-tumor Activity of Curcumin.
13. Debata, P.R., Begum, S., Mata, A., Genzer, O., Kleiner, M.J., Banerjee, P., and Castellanos, M. (2013) Anticancer Agents Med Chem,13,1508-13. Curcumin Potentiates The Ability of Sunitinib to Eliminate the VHL-lacking Renal Cancer Cells 786-O: Rapid Inhibition of Rb Phosphorylation as a Preamble to Cyclin D1 Inhibition.
14. Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Wefiel, J., Ma, S.Y., Azmitia, E.C., Banerjee, P., Flory, M., Cohen, I.L., London, E., Brown, T., Hare, C.K., and Wisniewski, T., (2013) Brain Res., 1512, 106-122. Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism.
15. Debata, P.R., Castellanos, M.R., Fata, J.E., Baggett, S., Rajupet, S., Szerszen, A., Begum, S., Mata, A., Murty, V.V., Opitz, L.M., and Banerjee, P. (2013) Gynecologic Oncology. 129, 145-153. A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells. Dec 9. doi:pii: S0090-8258(12)00952-3. 10.1016/j.ygyno.2012.12.005.
16. Mogha A, Guariglia, S.R., Debata, P.R., Wen, G.Y., and Banerjee, P. (2012) Translational Psychiatry (Nature group), 2(1), e66. doi:10.1038/tp.2011.58. Serotonin 1A Receptor-Mediated Signaling Through ERK and PKCα is Essential for Normal Synaptogenesis in Neonatal Mouse Hippocampus. (Among top ten downloaded articles).
17. Langone, P., Dolai, S., Debata, P.R., Curcio, G.M., Inigo, J.R., Raja, K., and Banerjee, P. (2012) Int J Cancer. 131, E569-E578. Coupling to A Cancer Cell-Specific Antibody Potentiates Tumoricidal Properties of Curcumin. Article first published online: 3 JAN 2012; DOI: 10.1002/ijc.26479.
18. Purkayastha, S., Ford, Kanjilal, B., J., Diallo, S., Inigo, J.D.R., Neuwirth, L., Elidrissi, A., Ahmed, Z., Wieraszko, A., and Banerjee, P. (2012) J Neurochem, 120, 396-407. Clozapine functions through the prefrontal cortex serotonin 1A receptor to heighten neuronal activity via calmodulin kinase II-NMDA receptor interactions.
19. Levano, K., Punia, V., Raghunath, M., Debata, P.R., Curcio, G., Mogha, A., Purkayastha, S., McCloskey, D., Fata, J., and Banerjee, P. (2012) J Neurochem, 120, 302-313. Atp8a1 Deficiency is Associated with Phosphatidylserine Externalization in Hippocampus and Delayed Hippocampus-Dependent Learning.
20. Debata, P.R., Ranasinghe, B., Berliner, A., Curcio, G.M., Tantry, S.J., Ponimaskin, E., and Banerjee, P. (2010) Biochem. Biophys. Res. Commun., 397, 401-406. Erk1/2-dependent phosphorylation of PKCalpha at threonine 638 in hippocampal 5-HT1A receptor-mediated signaling.
Current Doctoral Students
1. Tatyana Budylin (CUNY Doc. Prog. Biology/Neuroscience)
2. Juliet Baidoo (CUNY Doc. Prog. Biochemistry)
3. Angela Fried (CUNY Doc. Prog. Biochemistry)
Past Doctoral Students
1. Sumit Mukherjee (2018) (CUNY Doc. Prog. Biochemistry)
2. Alexandra Marsillo (2017) (CUNY Doc. Prog. Biology/Neuroscience)
3. Dan Kerr (2014) (CUNY Doc. Prog. Biology/Neuroscience)
4. Sreyashi Samaddar (2013) (CUNY Doc. Prog. Biology/Neuroscience)
5. Jarek Wegiel (2013) (CUNY Doc. Prog. Biology/Neuroscience)
6. Amit Mogha, Ph.D. (2011) (CUNY Doc. Prog. Biology/Neuroscience)
7. Phyllis Langone, Ph.D. (2011) (CUNY Doc. Prog. Biochemistry)
8. Kelly Levano, Ph.D. (2010) (CUNY Doc. Prog. Biochemistry)
9. Buddima Ranasinghe, Ph.D. (2009)(CUNY Doc. Prog. Biochemistry)
10. Baishali Kanjilal, Ph.D. (2008) (CUNY Doc. Prog. Biochemistry)
11. Mukti Mehta, Ph.D. (2007) (CUNY Doc. Prog. Biology/Neuroscience)
12. Farah Jayman, Ph.D. (2006) (Biochemistry Program)
13. Tatyana Adayev, Ph.D. (2004) (CUNY Doc. Prog. Biology/Neuroscience)
14. Hui-Ai Yang, Ph.D. (2000) (CUNY Doc. Prog. Biology/Neuroscience)
Past Post-Doctoral Associates
1. Priya Ranjan Debata, Ph.D
2. Sudarshana Purkayastha, Ph.D.
3. Tomasz Sobocki, Ph.D.
4. Indrani Ray, Ph.D.
