Post Doctoral Fellow - Neuroscience Department @ Tufts University School of Medicine
Post-doctoral Fellow Neurology Department @ Massachusetts General Hospital; Harvard Medical School
BSc (Hons), Biotechnology @
As an experienced neuroscientist, my current research focuses on the molecular mechanisms underlying chronic neurodegenerative disease and in particular the role that Traumatic Brain Injury (TBI) plays in the development of dementias such as Alzheimer’s disease (AD). My research which identified a novel molecular mechanism linking TBI to chronic neurodegeneration has been the subject of both national
As an experienced neuroscientist, my current research focuses on the molecular mechanisms underlying chronic neurodegenerative disease and in particular the role that Traumatic Brain Injury (TBI) plays in the development of dementias such as Alzheimer’s disease (AD). My research which identified a novel molecular mechanism linking TBI to chronic neurodegeneration has been the subject of both national and international media coverage.
My research career has given me the opportunity to pursue one of my passions which is to explore and elucidate the mechanisms responsible for disease pathogenesis and apply this knowledge to the pursuit of therapeutic interventions. In addition to my current research in the Alzheimer’s and neurotrauma fields I have a diverse background with experience in multiple disease areas including both neurodegenerative (AD & ALS), as well as rare neuromuscular diseases (NM, CFTD, HCM, MPD-1 & GSD-V). My extensive research background and considerable skill set attests to my highly adaptable nature and my life-long love of learning even in challenging new environments. As an activator, I thrive on the challenges associated with initiating new research projects that aim to answer disease-relevant mechanistic and therapeutic questions. I have worked successfully on numerous collaborations with both US and international scientists and thrive in multidisciplinary team based environments.
- Extensive experience characterizing large (ovine) and small (rodent) in-vivo models of disease.
- Behavioral Neuroscience (rodents)
- Stereotaxic Surgery (drug and viral delivery to rodent CNS)
- Controlled Cortical Impact (CCI) model of TBI
- Cellular and Molecular Biology, Protein Biochemistry
- Primary Neuronal Culturing, Lentiviral Packaging
- Immunohistochemistry and Imaging (WF and confocal)
Associate Scientist @ From January 2015 to Present (10 months) Tarrytown, NYPost Doctoral Fellow - Neuroscience Department @ 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 From May 2009 to December 2014 (5 years 8 months) BostonPost-doctoral Fellow Neurology Department @ 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
• 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. From April 2008 to April 2009 (1 year 1 month) BostonPost-doctoral Fellow Neurology Department @ 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. From October 2006 to April 2008 (1 year 7 months) BostonGraduate Research Assistant @ 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. From August 2003 to October 2006 (3 years 3 months) Perth, AustraliaPhD Candidate Researcher @ 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. From 2000 to 2006 (6 years) Perth, AustraliaContractor @ Sole tradership sub-contracting custom research services for Molecular Research Technologies (Pty Ltd). From 2002 to 2003 (1 year) Perth Area, Australia
PhD, Veterinary Biology and Biomedical Science @ Murdoch University From 2000 to 2006 BSc (Hons), Biotechnology @ Murdoch University From 1995 to 1999 Kendall Walker is skilled in: Western Blotting, Immunohistochemistry, Neuroscience, Cell, Confocal Microscopy, Protein Chemistry, ELISA, Molecular Biology, Genetics, Molecular Neuroscience, Cell Biology, In Vivo, Neurodegenerative..., in vitro, Neurobiology, CNS disorders, Traumatic Brain Injury, Behavioral Neuroscience, primary neuronal..., Assay Development, Alzheimer's disease, Rodent Surgery -..., Rodent Behavioral..., Molecular Biology - RNA..., Molecular Biology - DNA..., Molecular Biology-..., Lentivirus, Baculovirus, Immunocytochemistry, Northern Blotting, Molecular Cloning, PCR techniques- cDNA..., Recombinant protein..., Rare Diseases, Amyotrophic lateral..., Neurodegeneration, AAV adenoassociated..., Imaging, Grant Writing, Statistical Data..., Animal Models, cell culture, Cell Culture