Nikhil Panicker Laboratory

Research

The Panicker lab investigates the molecular mechanisms that drive pathology in Dementia with Lewy bodies (DLB), Parkinson’s Disease (PD), and Alzheimer’s Disease (AD), with the eventual goal of developing therapeutics that block or slow disease progression.We study cell-death pathways in neurodegenerative diseases, and how neuroinflammation (primarily mediated by microglial cells in the brain) contributes to the pathogenesis of neurologic disorders.

Our current projects explore the mechanisms and consequences of Nod-Like Receptor Protein-3 (NLRP3) inflammasome assembly by using cellular and molecular approaches in transgenic-mouse and iPSC disease models of DLB, PD and AD.

Selected Publications

1: Panicker N, Kam TI, Wang H, Neifert S, Chou SC, Kumar M, Brahmachari S, Jhaldiyal A, Hinkle JT, Akkentli F, Mao X, Xu E, Karuppagounder SS, Hsu ET, Kang SU, Pletnikova O, Troncoso J, Dawson VL, Dawson TM. Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease. Neuron. 2022 May 25:S0896-6273(22)00450-0. doi: 10.1016/j.neuron.2022.05.009. Epub ahead of print. PMID: 35654037.

2: Hinkle JT, Patel J, Panicker N, Karuppagounder SS, Biswas D, Belingon B, Chen R, Brahmachari S, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM. STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy. Proceedings of the National Academy of Sciences U S A. 2022 Apr 12;119(15):e2118819119. doi: 10.1073/pnas.2118819119. Epub 2022 Apr 8. PMID: 35394877; PMCID: PMC9169780.

3: Pirooznia SK, Wang H, Panicker N, Kumar M, Neifert S, Dar MA, Lau E, Kang BG, Redding-Ochoa J, Troncoso JC, Dawson VL, Dawson TM. Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in Parkinson's disease. Science Advances 2022 Apr;8(13):eabh1824. doi: 10.1126/sciadv.abh1824. Epub 2022 Apr 1. PMID: 35363524.

4: Panicker N, Ge P, Dawson VL, Dawson TM. The cell biology of Parkinson's disease. Journal of Cell Biology 2021 Apr 5;220(4):e202012095. doi: 10.1083/jcb.202012095. PMID: 33749710; PMCID: PMC8103423.

5: Sarkar S, Nguyen HM, Malovic E, Luo J, Langley M, Palanisamy BN, Singh N, Manne S, Neal M, Gabrielle M, Abdalla A, Anantharam P, Rokad D, Panicker N, Singh V, Ay M, Charli A, Harischandra D, Jin LW, Jin H, Rangaraju S, Anantharam V, Wulff H, Kanthasamy AG. Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease. Journal of Clinical Investigaton 2020 Aug 3;130(8):4195-4212. doi: 10.1172/JCI136174. PMID: 32597830; PMCID: PMC7410064.

6: Saminathan H, Charli A, Luo J, Panicker N, Gordon R, Hostetter JM, Jin H, Anantharam V, Kanthasamy AG, Kanthasamy A. Fyn kinase mediates pro-inflammatory response in a mouse model of endotoxemia: Relevance to translational research. European Journal of Pharmacology 2020 Aug 15;881:173259. doi: 10.1016/j.ejphar.2020.173259. Epub 2020 Jun 18. PMID: 32565338; PMCID: PMC7483871.

7: Panicker N, Kanthasamy A, Kanthasamy AG. Fyn amplifies NLRP3 inflammasome signaling in Parkinson's disease. Aging (Albany NY). 2019 Aug 27;11(16):5871-5873. doi: 10.18632/aging.102210. Epub 2019 Aug 27. PMID: 31454793; PMCID: PMC6738402.

8: Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019 Aug 21;103(4):627-641.e7. doi: 10.1016/j.neuron.2019.05.035. Epub 2019 Jun 26. PMID: 31255487; PMCID: PMC6706297.

9: Panicker N, Sarkar S, Harischandra DS, Neal M, Kam TI, Jin H, Saminathan H, Langley M, Charli A, Samidurai M, Rokad D, Ghaisas S, Pletnikova O, Dawson VL, Dawson TM, Anantharam V, Kanthasamy AG, Kanthasamy A. Fyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia. Journal of Experimental Medicine. 2019 Jun 3;216(6):1411-1430. doi: 10.1084/jem.20182191. Epub 2019 Apr 29. PMID: 31036561; PMCID: PMC6547864.

10: Harischandra DS, Rokad D, Neal ML, Ghaisas S, Manne S, Sarkar S, Panicker N, Zenitsky G, Jin H, Lewis M, Huang X, Anantharam V, Kanthasamy A, Kanthasamy AG. Manganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein. Science Signaling. 2019 Mar 12;12(572):eaau4543. doi: 10.1126/scisignal.aau4543. PMID: 30862700; PMCID: PMC6435331.

11: Kam TI, Mao X, Park H, Chou SC, Karuppagounder SS, Umanah GE, Yun SP, Brahmachari S, Panicker N, Chen R, Andrabi SA, Qi C, Poirier GG, Pletnikova O, Troncoso JC, Bekris LM, Leverenz JB, Pantelyat A, Ko HS, Rosenthal LS, Dawson TM, Dawson VL. Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson's disease. Science. 2018 Nov 2;362(6414):eaat8407. doi: 10.1126/science.aat8407. PMID: 30385548; PMCID: PMC6431793.

12: Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nature Medicine 2018 Jul;24(7):931-938. doi: 10.1038/s41591-018-0051-5. Epub 2018 Jun 11. PMID: 29892066; PMCID: PMC6039259.

13: Sarkar S, Malovic E, Harishchandra DS, Ghaisas S, Panicker N, Charli A, Palanisamy BN, Rokad D, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson's disease. NPJ Parkinsons Disease. 2017 Oct 17;3:30. doi: 10.1038/s41531-017-0032-2. PMID: 29057315; PMCID: PMC5645400.

14: Panicker N, Dawson VL, Dawson TM. Activation mechanisms of the E3 ubiquitin ligase parkin. Biochemical Journal 2017 Aug 30;474(18):3075-3086. doi: 10.1042/BCJ20170476. PMID: 28860335.

15: Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017 Jan 26;541(7638):481-487. doi: 10.1038/nature21029. Epub 2017 Jan 18. PMID: 28099414; PMCID: PMC5404890.

16: Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, Ge P, Umanah GE, Brahmachari S, Shin JH, Kang HC, Zhang J, Xu J, Chen R, Park H, Andrabi SA, Kang SU, Gonçalves RA, Liang Y, Zhang S, Qi C, Lam S, Keiler JA, Tyson J, Kim D, Panicker N, Yun SP, Workman CJ, Vignali DA, Dawson VL, Ko HS, Dawson TM. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science. 2016 Sep 30;353(6307):aah3374. doi: 10.1126/science.aah3374. PMID: 27708076; PMCID: PMC5510615.

17: Gordon R, Neal ML, Luo J, Langley MR, Harischandra DS, Panicker N, Charli A, Jin H, Anantharam V, Woodruff TM, Zhou QY, Kanthasamy AG, Kanthasamy A. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration. Nature Communications. 2016 Oct 5;7:12932. doi: 10.1038/ncomms12932. PMID: 27703142; PMCID: PMC5059486.

18: Gordon R, Singh N, Lawana V, Ghosh A, Harischandra DS, Jin H, Hogan C, Sarkar S, Rokad D, Panicker N, Anantharam V, Kanthasamy AG, Kanthasamy A. Protein kinase Cδ upregulation in microglia drives neuroinflammatory responses and dopaminergic neurodegeneration in experimental models of Parkinson's disease. Neurobiology of Disease. 2016 Sep;93:96-114. doi: 10.1016/j.nbd.2016.04.008. Epub 2016 May 2. PMID: 27151770; PMCID: PMC4995107.

19: Panicker N, Saminathan H, Jin H, Neal M, Harischandra DS, Gordon R, Kanthasamy K, Lawana V, Sarkar S, Luo J, Anantharam V, Kanthasamy AG, Kanthasamy A. Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease. Journal of Neuroscience 2015 Jul 8;35(27):10058-77. doi: 10.1523/JNEUROSCI.0302-15.2015. PMID: 26157004; PMCID: PMC4495236.

20: Jin H, Kanthasamy A, Harischandra DS, Kondru N, Ghosh A, Panicker N, Anantharam V, Rana A, Kanthasamy AG. Histone hyperacetylation up-regulates protein kinase Cδ in dopaminergic neurons to induce cell death: relevance to epigenetic mechanisms of neurodegeneration in Parkinson disease. Journal of Biological Chemistry 2014 Dec 12;289(50):34743-67. doi: 10.1074/jbc.M114.576702. Epub 2014 Oct 23. PMID: 25342743; PMCID: PMC4263877.