Kendall Walker PhD.

Responsible for managing multiple concurrent pre-clinical research projects for biotech, pharma, & non-profit organizations focused on Huntington’s Disease, Parkinson’s Disease, Muscular Dystrophy & Spinal Muscular Atrophy. Direct all aspects of client projects from advising on experimental design, preparing study proposals & pricing, resource allocation, analysis of study data & preparation of reports & client presentations. Lead a team of 5-8 research associates (RA’s) to facilitate the successful completion of client studies. Responsible for hiring & training of new RA’s for the Neurodegenerative Disease (NDG) group at PsychoGenics Inc. Co-manage studies involving molecular, biochemical, behavioral & electrophysiological phenotyping of novel & commercial murine NDG models to investigate underlying disease biology & identify therapeutically relevant biomarkers. Execute pre-clinical ligand validation studies (MTDs, PK/PD) & also pre-clinical ligand efficacy studies in murine NDG models via traditional dosing routes or stereotaxic administration to the CNS. Direct behavioral phenotyping of NDG mouse models utilizing standard behavioral assays as well as PGI proprietary cubes technologies to identify critical behavioral features contributing to disease biology & are suitable for assessment of investigational compounds. Perform stereotaxic surgical R&D projects in a technical specialist capacity, with an emphasis on developing & refining surgical techniques for clients requested method development as well as internal R&D efforts. This includes producing hand-made infusion apparatuses to ensure test article compatability & improve compound diffusion parameters. Validated & trained RA’s in Parkinson’s disease surgical models including chemical lesioning (4-point 6’OHDA) & alpha-synuclein seeding/prion spreading models. Responsible for all client as well as internal R&D efforts based around alpha-synuclein seeding/prion spreading surgical models.

Laboratory specializes in the identification of BACE1 regulatory mechanisms for the treatment of Alzheimer’s Disease (AD). Advisor: A/Prof. Giuseppina Tesco I am currently investigating the pathological role of BACE1 elevation as well as the therapeutic potential of BACE1 regulation following experimental TBI. Additionally, I am also spearheading an innovative project that is focused on dissecting the role of a novel molecular target implicated in the anxiety and depression circuitry in the rodent brain. Key Research Highlights: • Demonstrated a crucial role for the BACE1 regulating molecule (GGA3) in the aging brain • Identified & published the first known molecular mechanism (caspase mediated depletion of GGA3 & GGA1) responsible for regulating BACE1 activity & Aβ production following TBI. • Demonstrated that GGA3 haploinsufficiency (as occurs in the brains of AD patients) is an important risk factor for the development of chronic neurodegeneration following TBI. • Developed an improved fluorimetric method for measuring BACE1 activity in mouse brain tissue, a notoriously difficult assay to perform accurately. Published J. Neurosci. 2012. • Identified a novel behavioral phenotype associated with GGA3 induced elevation of BACE1 in the GGA3KO mouse model (manuscript in preparation) • Collaborated on an additional four research projects with A/Prof. Chris Dulla, TUSM; Prof. Philip G.Haydon, TUSM; Prof. Steven J Moss, TUSM and Dr. Luca Longhi, Uni. of Milan • Manuscript review: Nat. Sci. Rep., Open Neurol. J. and J. Neurosci. • Wrote &/or assisted in the writing of grants for AHAF, CAF, DOD &NIH • Responsible for the direct management of a research technician and daily supervision and training of all laboratory staff. Teaching of graduate student laboratory boot camp courses. Designed & implemented all Animal Ethics, Biohazard & EHS protocols for the lab Techniques used are listed under individual projects

Molecular Neurodegeneration Laboratory, Genetics and Aging Unit. Lab specializes in the identification of BACE1 regulatory mechanisms for therapeutic treatment of Alzheimer’s DiseaseAdvisor: A/Prof. Giuseppina Tesco Research focuses on the role of GGA3 mediated BACE1 stabilization in Alzheimer’s Disease (RO1AG025952-01A1) • Research demonstrated an important molecular mechanism for BACE1 elevation and neurotoxic Aβ production (caspase-mediated depletion of the intracellular trafficking protein GGA3) and provides a novel therapeutic target for AD treatment. - Demonstrated that the normal cellular function of GGA3 is to bind BACE1 and traffic it to the lysosomes for degradation. - This research explains a crucial mechanism by which caspase-mediated depletion of GGA3 results in increased BACE1 activity and Aβ production in vitro and provides an alternative to small molecule BACE1 inhibitors for the treatment of AD. [Published J. Biol. Chem. 2010] • Collaborated with Drs. Michael Whalen and Rebekah Mannix of the Centre for Neuroscience at MGH to examine the effect of APOε4 on outcome following TBI. Performed Aβ ELISA’s that demonstrated that the APOε4 gene regulated soluble Aβ production following traumatic brain injury only in mature mice not immature mice demonstrating an important age-dependent effect of APOε4 on functional outcome. [Published J. Cereb. Blood Flow and Metab. 2010] Techniques used include: neuronal culturing from rodents, rodent surgery (stereotaxic and lesioning), immunohistochemistry, quantitative confocal analysis, ELISA and western blotting.

Cecil B Day Neuromuscular Lab, Massachusetts General Hospital. Lab focuses on the genetics of neuromuscular and neurological disorders, in particular ALS. Advisor: Prof. Robert H Brown Jr Angel Fund Fellow 2007 - awarded financial support by the independent ALS charity. Research focuses on RVG peptide delivery of IGF-1, VEGF and mutant SOD1 siRNA’s to the CNS for the treatment of ALS • Performed in vitro studies to silence mutant G93A SOD1 using siRNAs electrostatically coupled to a novel cell penetrating peptide based upon the rabies virus glycoprotein (RVG). • Designed and expressed recombinant neurotrophic factors IGF-1 and VEGF with the RVG sequence as a protein transduction domain using the Baculovirus expression system (BEVS). • Supervised a graduate student from Harvard College for the practical component of her degree. Techniques used include: plasmid design and construction, recombinant protein production using BEVS, gene silencing using siRNA’s, confocal analysis, western blotting and dosing via i.p. and tail vein in G3ASOD1 mice.

Molecular Neurogenetics Laboratory, Western Australian Institute for Medical Research (WAIMR) specializes in the genetics and biochemistry of rare neuromuscular diseases.Lab Head: Prof. Nigel G Laing • Identified disease-causing mutations for nemaline myopathy and congenital fibre type disproportion. [Published Ann. Neurol. 2004; Ann. Neurol. 2007] • Collaborated with the Western Australian Health Department to optimize their southern blot assay for myotonic dystrophy (DM1) in clinical samples. • Produced and purified recombinant thin filament proteins (skeletal α-actin, α-tropomyosin-1 and α-tropomyosin-3) using the BEVS for functional studies of congenital myopathy pathogenesis. [Published Biochem. Biophys. Res. Comm 2003; J. Neuropathol. Exp. Neurology 2008] • Initiated and completed a candidate gene-screening project of an Australasian cohort of non-SOD1 familial and sporadic ALS patients. This study was awarded a 25K grant-in-aid from the Motor Neuron Disease Research Institute (MNDRI) of Australia. •Responsible for training research assistants and graduate students. Co-edited manuscripts for Sciencedit, a company specializing in editing and writing assistance for researchers with english as a second language. Techniques used include: recombinant protein production and purification (BEVS), DNA/RNA extraction (blood and tissue), std and mutagenic PCR, sequencing, SSCP, southern blotting.

This research Institute focuses on uncovering the genetic and environmental causes of disease. Advisors: Prof. Nigel G Laing & Prof. John Howell •Characterized the molecular and biochemical phenotype of the ovine model of McArdle’s disease, a metabolic disease affecting skeletal muscle. Analyzed the ability of butyric acid to re-express the fetal isoform of glycogen phosphorylase in muscle as a potential therapeutic strategy for McArdle’s disease. •Demonstrated that exploitation of gene redundancy through the re-expression of the fetal isoform of glycogen phosphorylase via myotoxin induced muscle regeneration is a potential therapeutic strategy. •Demonstrated that injection of AAV’s expressing muscle glycogen phosphorylase into the muscle of McArdles’ affected sheep was able to restore glycogen degradation and the expression of functional glycogen phosphorylase and is valid therapeutic strategy. [Published Neuromusc. Disord. 2008] •Trained research assistant/junior graduates. Designed/implemented vivisection (animal ethics) registrations. Techniques used include: recombinant protein production (BEVS), Purification of recomb. and non recomb. proteins (Affinity, ion exchange, size exclusion), polyclonal antibody production and purification (rodents), northern blotting, nuclease protection assays, western blotting, and microarray.

Sub-contractor of custom research services for Molecular Research Technologies (Pty Ltd).

BSc. (Hons), Murdoch University. Bachelor of Science in Biotechnology with First Class Honors in Veterinary Biology and Biomedical Science Thesis title: Expression of glycogen phosphorylase isoenzymes during ovine fetal development. Supervisors: Prof. Nigel G Laing (CNND) and A/Prof. Clive Huxtable (Murdoch University). Examiners: Prof. Frank L Mastaglia, Centre for Neuromuscular and Disorders, Sir Charles Gairdner Hospital. Dr Wayne Green, Dept of Veterinary Biology and Biomedical Science, Murdoch University, Perth Western Australia.

Murdoch University, Western Australian Institute for Medical Research and Centre for Medical Research (University of Western Australia). Thesis title:”Characterization of the Ovine Model of McArdle’s Disease: Development of Therapeutic Strategies.” Supervisors: Prof. Nigel G Laing (WAIMR) and Emeritus Prof. John McC Howell (Murdoch University). Examiners: 1. Dr. David Thorburn, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville Victoria. 2. Prof. Antoni L Andreu, Centre d’Investigacio en Bioquimica I Biologia Molecular, University Hospital Vall d’Hebron, Barcelona Spain. 3. Dr Philip Sheard, Dept of Physiology, Otago School of Medical Sciences, Dunedin New Zealand.