Our research aims to understand the mechanisms of neural death and identify therapeutic targets in nervous system diseases, particularly stroke, frontal temporal dementia, and Parkinson’s disease. The central focus of our research is on mitochondrial function and autophagy. We use different potential therapeutic agents to restore the process of autophagy and mitochondrial function in neural and non-neural cells for neuroprotection in stroke and neurodegenerative diseases. One area of focus is the modulation of progranulin (PGRN) and Cathepsin D (CTSD) and functional interactions of a neuronal protein, sulfotransferase 4a1 (SULT4a1), with components of lysosomes and mitochondria in stroke and neuronal diseases. Other focus areas in our laboratory include understanding the role of poly(ADP-ribose) (PAR) on inflammation, cell death signaling, and regulation of dynamics of proteins like TDP-43. We also study how PAR-signaling alters glycolysis, mitochondrial function, and fatty acid oxidation and how age affects these processes to change the stroke outcome. We use mouse neuronal culture, iPSC-derived neurons, animal models (tMCAO, dMCAO, and BCCAO) of stroke, genetic models of FTD/ALS combined with advanced small animal imaging technology, bioenergetics flux studies, metabolomics, gene targeting, and high throughput proteomics to distinguish the dominant pathological network. We aim to characterize molecular mechanisms that initiate cell death and identify novel targets for therapeutic interventions in stroke and neurodegenerative disease.

We also study the impact of microplastics on brain function and how exposure to this potential environmental hazard increases the susceptibility to stroke and neural diseases.

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). PMID: 27708076

Wang Y, An R, Umanah GK, Park H, Nambiar K, Eacker SM, Kim BW, Bo L, Harraz MM, Chang C, Chen R, Wang JE, Kam TI, Jeong JS, Xie Z, Neifert S, Qian J, Andrabi SA, Blackshaw S, Zhu H, Song H, Ming GL, Dawson VL, Dawson TM. A Nuclease that Mediates Cell Death induced by DNA Damage and Poly(ADP-ribose) Polymerase-1. Science. 2016 Oct 7;354(6308). PMID: 27846469

Zhang J, Wang H, Sherbini O, Ling-Lin Pai E, Kang SU, Kwon JS, Yang J, He W, Wang H, Eacker SM, Chi Z, Mao X, Xu J, Jiang H, Andrabi SA, Dawson TM, Dawson VL. High-Content Genome-Wide RNAi Screen Reveals CCR3 as a Key Mediator of Neuronal Cell Death. eNeuro. 2016 Oct 24;3(5). PMID: 27822494

Samanta D, Park Y, Andrabi SA, Shelton LM, Gilkes DM, Semenza GL. PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis. Cancer Res. 2016 Aug 1;76(15):4430-42. PMID: 27280394

Stevens DA, Lee Y, Kang HC, Lee BD, Lee YL, Bower A, Jiang H, Kang SU, Andrabi SA, Dawson VL, Shin JH, Dawson TM. Parkin Loss Leads to PARIS-dependent declines in mitochondrial mass and respiration. PNAS. 2015 Sep 15;112(37):11696701. PMID 26324925

Kageyama Y, Hoshijima M, Seo K, Bedja D, Shah P, Andrabi SA, Chen W, Höke A, Dawson VL, Dawson TM, Gabrielson K, Kass DA, Iijima M, Sesaki H. (2014). Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain. EMBO J. 2014 Oct 27. PMID: 25349190

Andrabi SA*, Umanah GKE, Chang C, Stevens DA, Karuppagounder SS, Gagne JP, Poirier GG, Dawson VL, Dawson TM*. Poly (ADP-Ribose) Polymerase Dependent Energy Depletion Occurs Through Inhibition of Glycolysis. PNAS. 2014 Jul 15;111(28):10209-14. PMC4104885. *Corresponding Author.

Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Min-Sik Kim, Jun Zhong, Kumar M, Andrabi SA, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s disease. Cell. 2014 Apr 10;157(2):472-85. PMC4040530

Andrabi SA, Hochul K, Jean-François Haince, Yun-Il Lee, Jian Zhang, Zhikai Chi, Andrew B. West, Raymond C. Koehler, Guy G. Poirier, Ted M. Dawson, Valina L. Dawson. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with parthanatos (Poly (ADP-ribose) dependent cell death). Nature Medicine. 2011 Jun;17(6):692-9. PMC3709257

Kang HC, Lee Yl, Shin J, Andrabi SA, Lee BD, Gagne JP, Chi Z, Lee YJ, Ko HS, Poirier GG, Dawson VL, Dawson TM. Iduna is a poly (ADP-Ribose) (PAR)- dependent E3 ubiquitin ligase that regulates DNA damage. PNAS. 2011 Aug 23;108(34):14103-8. PMC3161609