andrabiAssociate Professor

Areas of Interest
Stroke, mitochondrial bioenergetics, cell death signaling and neurodegeneration

PubMed

Biography

I received my Ph.D. (Dr.rer.nat) in Neurobiology from the Otto-von-Guericke University, Germany, and postdoctoral training in Neurology / Neuroscience from Johns Hopkins University School of Medicine. I served as a faculty in the Department of Neurology Johns Hopkins University School of Medicine before joining UAB in 2016.  I am currently an Associate Professor in the Department of Pharmacology and Toxicology with a joint appointment in the Department of Neurology.

Research Interests

We study mechanisms of mitochondrial and bioenergetic alterations leading to cell death in nervous system diseases particularly in stroke and Parkinson’s disease. Major focus is on poly (ADP-ribose) polymerase-1, mitochondrial sirtuins, hexokinase 1&2 and apoptosis inducing factor, and how changes in the function, regulations and expression of these proteins lead to alterations in glycolytic, mitochondrial and fatty acid oxidations pathways. Our research on hexokinase suggest that glycolysis-independent functions of hexokinase are critical in regulating mitochondrial function in nutrient deficit and hypoxic conditions. We have employed innovative approaches to demonstrate how poly(ADP-ribose) (PAR)-dependent modification of hexokinase can cause glycolytic defects, mitochondrial alteration and redox imbalance in neural cells. We have vested efforts to identify this PAR dependent modification of hexokinase as a potential target of therapeutic intervention in stroke.

We use Oxygen Glucose Deprivation (OGD) in neuronal culture, and transient middle cerebral artery occlusion (MCAO), distal MCAO and bilateral carotid artery occlusion in rodents as models of stroke in combination with advanced imaging technology, live-imaging, bioenergetics flux studies, metabolomics, viral-mediated gene targeting and high throughput proteomic studies to distinguish the dominant pathological signaling network.

Other emerging areas of research in our laboratory on a brain specific sulfotransferase 4A1 demonstrate that this protein may have novel functions in the brain converging mitochondrial bioenergetics with cell death/survival signaling in stroke and neural injury. Other areas of focus in our laboratory is to help understanding the pathophysiological roles of bioenergetics and mitochondrial alteration in Parkinson’s disease progression. Our goal is to characterize molecular mechanisms that initiate cell death, and identify novel targets for therapeutic interventions in stroke and Parkinson’s disease.

Selected Publications

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

Education

Ph.D., Otto-von-Guericke University, Germany

Postdoctoral Fellowships
Postdoctoral Fellow, Johns Hopkins University School of Medicine

Contact

Office Location
Volker Hall 242

Phone
205-934-9318

Email
sandrabi@uab.edu