Research Assistant Professor

ANGELIKI MARIA NIKOLAKOPOULOU PhD

Email: ***********@*****.***, ********@***.***

Telephone number: 951-***-****

EDUCATION

**** *** ** *************, ********** Biological Sciences, The Open University, Milton Keynes, UK

2001 BS in Biology, Department of Biology, University of Crete, Greece

RESEARCH EXPERIENCE

2013 – Present Assistant Professor of Research, Department of Physiology and Neuroscience, University of Southern California, Los Angeles, CA 90089

Responsible for the design and execution of experiments as first author of three major projects related to neurodegeneration and/or blood brain barrier deficits. Contributing expertise and participating in the design of studies related to animal models of AD (ApoE, 5xFAD, and tau) and ALS (SOD1G93A and SOD1G85R).

Leading projects related to blood-brain barrier deficits on human PD samples

Performing experiments using immunofluorescence, electron microscopy, cell culture, FACS, MACS, CSF extraction, western blotting, LDFs, cell transfections, pharmacological agents, microvessel isolation, ELISAs, multiplex assays, behavioral studies (rotarod, grip strength) etc.

Writing and reviewing grants and scientific papers

Supervising/managing three technicians and PhD students

2011 – 2013 Associate Specialist, Department of Biomedical Sciences, University of California Riverside, Riverside, CA 92521

Elucidated the role of astrocytic ephrinB1 in traumatic brain injury by showing that its depletion causes synaptic changes and affects STAT3 upregulation by using immunofluorescence, cell culture, cell transfections and RT-PCR

Obtained funding from the National Multiple Sclerosis Society to investigate the effects of astrocytic ephrinB1 ablation in demyelination and remyelination in an animal model of Multiple Sclerosis (cuprizone) (PI Nikolakopoulou)

2009 – 2011 Postdoctoral Associate, Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029

Conceived, designed, and executed in vitro studies on the role of trypsin in neuroprotection against excitotoxicity in Alzheimer’s Disease, especially in the absence of presenilin1 or presence of FAD mutations. Working experience with PS1 KO, PS1I213T, PS1M146V models.

Performed various biochemical and molecular biology studies including biotinylation, Western blotting, cell transfections and viral infections using lentiviruses, BacMam and HSV viruses.

2006 – 2009 Postdoctoral Fellow, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44114

Designed and executed experiments related to Multiple Sclerosis studies to identify whether activated microglia can enhance neurogenesis in vitro and identified microglia-secreted factors that promote white matter neurogenesis.

Characterized the developmental expression of β-tubulin4 in the fetal human brain

2005-2006 Postdoctoral Fellow, Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 92697.

Performed overexpression of genes by electroporation in the tadpole optic tectum and elucidated synaptic plasticity developmental changes related to BDNF and its receptor, TrkB, by pre-embedding immunoelectron microscopy.

Used unbiased quantification of immunohistochemical data combining stereology and image analysis.

SKILLS AND EXPERTISE

Extensive experience working with human samples and mouse models of Alzheimer’s Disease, Multiple Sclerosis, traumatic brain injury, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis.

Extensive experience in neuroanatomy

Specialized skills in the study of the BBB and brain vasculature: stereotaxic injections of AAV and small molecules, microvessel isolation, cerebrospinal fluid (CSF) extraction and blood collection, laser doppler flowmetry (LDF), cranial windows, etc.

Broad expertise with ex vivo and in vitro culture systems: brain tissue explants, primary cells (neurons, astrocytes, oligodendrocytes, microglia, pericytes), stem cells, and cell lines. Cell health and toxicity assays to test pharmacological agents, neuroprotective factors and toxic compounds, such as APC, glutamate, fibrinogen, thrombin, etc.

Experience in biochemistry techniques (western blotting, immunoprecipitation and biotinylation)

Experience with gene expression (microarray experiments and qPCR), gene silencing (siRNA, shRNA), DNA cloning, and gene delivery (lentivirus, HSV, BacMam) techniques

Expert in immunohistochemical techniques, including pre-embedding immunoelectron microscopy using chick brains, tadpole optic tecta, rat and mouse brains, and human tissues; developed fixation, blocking, sectioning, antibody specificity and retrieval methodology for a wide variety of markers for the abovementioned tissues.

Experience with various microscopy approaches, including widefield, confocal, and transmission electron microscopy, with image analysis and processing software and stereological or morphometric techniques.

Experience with magnetic cell sorting (MACS) and flow cytometry (FACS) of brain cell types

A problem solver by nature and a scientist with deep desire to participate in drug development to address patient’s unmet needs. I can meet deadlines, be flexible and innovative, eager to expand my knowledge and experience base, a reliable team player, an effective communicator, an experienced mentor and manager, and an individual who consistently delivers on results.

Analytical skills using spreadsheets, basic bioinformatics and statistical analysis applications. Extensive experience with Microsoft Office, GraphPad Prism, FlowJo, Adobe Photoshop and Illustrator

PEER REVIEWED PUBLICATIONS

1.Koeppen J.*, Nguyen A.Q.*, Nikolakopoulou A.M., Garcia M., Hanna S., Woodruff S., Obenaus A., Ethell I.M. Functional consequences of excessive synaptogenesis following astrocyte-specific deletion of ephrin-B1 in the adult hippocampus (*equal contribution) (In Press, Journal of Neuroscience)

2.Montagne A*, Nikolakopoulou AM*, Zhao Z*, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A, Lawson EJ, Wang Y, Mack WJ, Thompson PM, Schneider JA, Varkley J, Langen R, Mullins E, Jacobs RE and Zlokovic BV. Pericytes play a critical role in the white matter health and disease (*equal contribution) Nature Medicine, https://doi.org/10.1038/nm.4482.

3. Salehi P, Ge MX, Gundimeda U, Baum LM, Cantu HL, Lavinsky J, Tao L, Myint A, Cruz C, Wang J, Nikolakopoulou AM, Abdala C, Kelley MW, Ohyama T, Coate TM, Friedman RA Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea. PLoS Genet13(10): e1007048. https://doi.org/10.1371/journal.pgen.1007048

4. Nikolakopoulou AM, Zhao Z, Montagne A, Zlokovic BV. Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling. PLoS ONE 12(4): e0176225. https://doi.org/10.1371/journal.pone.0176225

5. Nikolakopoulou AM*, Georgakopoulos A, and Robakis NK*. Presenilin1 promotes trypsin-induced neuroprotection via the PAR2/ERK signaling pathway. Effects of presenilin1 FAD mutations (2016) Neurobiology of Aging, 42:41-9, doi:10.1016/j.neurobiolaging.2016.02.028 *corresponding authors

6. Nikolakopoulou AM, Koeppen J, Garcia M, Leish J, Obenaus A and Ethell IM. Astrocytic ephrin-B1 regulates synapse remodeling following traumatic brain injury (2016) ASN Neuro 2016 Feb 29;8(1). pii: 1759091416630220. doi: 10.1177/1759091416630220

7. Nikolakopoulou AM, Dutta R, Chen Z, Miller RH and Trapp BD. Activated Microglia Enhance Neurogenesis in Optic Nerve Cell Cultures via Trypsinogen secretion. (2013) PNAS, 110(21): 8714-8719

8. Nikolakopoulou AM, Meynard MM, Marshak S and Cohen Cory S. Synaptic Maturation of the Xenopus Retinotectal System: Effects of Brain Derived Neurotrophic Factor on Synapse Ultrastructure (2010) Journal of Comparative Neurology, 518(7): 972-989

9. Manitt C, Nikolakopoulou AM, Almario DR, Nguyen SA and Cohen-Cory S. Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain. (2009) Journal of Neuroscience 29(36):110**-*****

10. Marshak S., Nikolakopoulou AM, Dirks R., Martens G. and Cohen-Cory S. Cell autonomous TrkB signaling in presynaptic retinal ganglion cells mediates axon arbor growth and synapse maturation during the establishment of retinotectal synaptic connectivity (2007) Journal of Neuroscience 27(10): 2444-2456

11. Nikolakopoulou AM, Dermon C.R., Panagis L., Pavlidis M. and Stewart M.G. Passive avoidance training is correlated with decreased cell proliferation in the chick hippocampus (2006) European Journal of Neuroscience 24: 2631-2642

12. Nikolakopoulou AM, Parpas A., Panagis L., Zikopoulos B., Dermon C.R. Early post-hatching sex differences in cell proliferation and survival in the quail telencephalic ventricular zone and intermediate medial mesopallium (2006) Brain Research Bulletin 70 (2): 107-116

13. Nikolakopoulou AM, Davies H.A. and Stewart M.G. Passive avoidance training decreases synapse density in the hippocampus of the domestic chick (2006) European Journal of Neuroscience 23: 1054-1062

14. Hu B, Nikolakopoulou AM and Cohen-Cory S. BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo (2005) Development 132(19): 4285-98

MANUSCRIPTS UNDER REVIEW-REVISION

1. Nikolakopoulou AM*, Kisler K*, Lazic D, Kong P, Sagare AP, Lawson E, Wang M, Makshanoff J, Zhao Z, Zlokovic BV. Pericyte ablation in a pericyte-specific inducible Cre mouse model; effects on the blood-brain barrier. (Under review, Nature) (*equal contribution).

MANUSCRIPTS IN PREPARATION

1.Zhao Z*, Nikolakopoulou AM*, Rege S, Montagne A, Ma Q, Sagare AP, Wang Y, Makshanoff J, Ahuja A, Chuqui Owens N, Herz J, Zlokovic BV Endothelial LRP1 controls cerebrovascular integrity and neuronal survival via CypA-MMP9-NFkB pathway (In preparation) (*equal contribution).

2.Lazic D, Sagare AP, Nikolakopoulou AM, Lawson EJ, Zlokovic BV. 3K3A-activated protein C treatment attenuates amyloid β-mediated brain disorder in 5xFAD mice (In preparation)

3. Montagne A, Sagare AP, Lazic D, Nikolakopoulou AM, Lawson EJ, Huuskonen M, Zuniga E, Rege S, Zlokovic BV. Amyloid-independent cerebrovascular dysfunctions in aged APOE4 targeted replacement mice (In preparation)

4. Nikolakopoulou AM* and Ethell IM. Depletion of astrocytic ephrinB1 affects neurogenesis and oligodendrogenesis and inhibits remyelination after cuprizone-induced demyelination (Corresponding author, In preparation).

MANAGERIAL/TEACHING EXPERIENCE

2014-to date: Training and management of two technicians and one PhD student at USC.

2011-2013: Training and supervision of one PhD student and 1 undergraduate student at UCR,

Department of Biomedical Sciences

2005-2006: Designed and supervised the research projects of two undergraduate students at the

University Of California in Irvine (UCI), Department of Neurobiology and Behavior

2004: Teaching assistant for lab course in Physiology during OU Residential School

2003: Teaching assistant for lab course in Biochemistry during OU Residential School

2001: Teaching Assistant for the class Physiology of Animals

MEMBERSHIPS

2001-present Member of the Society for Neuroscience.

2001-2004 Member of the British Neuroscience Association

2001-2004 Member of the Federation of European Neurosciences.

OTHER SKILLS

Ad hoc reviewer: Brain Research Bulletin, Circulation, Cell, Nature, Nature Neuroscience, Stroke, Science, Brain Pathology, and many other Neuroscience journals

Speaks French (advanced), Italian (advanced), German (basic) and Greek (native)

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