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Curriculum Vitae

Education & Employment

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2024 - present

University of California, San Francisco

Resident, Department of Laboratory Medicine

Research-track trainee in the principles of laboratory medicine including microbiology, hematology, transfusion, mass spectrometry, informatics, medical diagnostics

2017 - 2022

University of Cambridge & National Institutes of Health

Doctor of Philosophy, Chemistry

NIH-Cambridge PhD programme awardee

NIH mentor: Byron Caughey, senior investigator

Cambridge supervisor: Professor Michele Vendruscolo

Thesis: amyloid seeding assays for the selective amplification of tau aggregates from human brain homogenates

2015 - 2024

University of Illinois at Chicago

Doctor of Medicine

Medical scientist training program awardee

2009 - 2013

James Madison University

Bachelor of Science, Chemistry and Biotechnology

Double baccalaureate, cum laude, with distinction in chemistry

Research Experience

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James Madison University
department of chemistry

I found my love for basic science after wandering into Professor Gina MacDonald's office. Gina infected me with the research bug and we worked on many projects together. I learned protein purification, thermal stability assays, fluorescence spectroscopy, FTIR spectroscopy, and circular dichroism spectroscopy in her lab. Gina introduced me to the Hofmeister series of ions on which we published two papers describing their effects as they relate to the solvation and thermal stability of model proteins. My first 'clincher' experiment that I designed on my own - an in-situ hydrogen-deuterium exchange experiment that allowed us to visualize protein solvation through real-time FTIR measurements - cemented my drive to pursue science as a career.

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National Institutes of Health Rocky Mountain Laboratories

Under the supervision of Senior Investigator Byron Caughey, I worked with a diverse team of postdoctoral fellows, postbaccalaureates, staff scientists and laboratory managers to develop three assays capable of strain-specific discrimination of tauopathies. With the team, I authored ​a paper utilizing the training I garnered from Gina's lab that afforded million-fold sensitivy enhancement in proteopathic seeding assays. Our work on tau amplification assays was disseminated through three publications, at many conferences, and through a patent on which I am co-inventor. I bolstered my technical experience with new experience in transmission electron microscopy, fluorescence, protein substrate design, purification, and quality control, and scientific manuscript preparation.

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University of Cambridge Centre for Misfolding Diseases

After transitioning my PhD project from the NIH to Cambridge, I sought to explain the mechanisms of tau strain propagation with Professor Michele Vendruscolo at the Centre for Misfolding Diseases. We showed near-perfect propagation of AD-tau in a human brain homogenate-seeded assay. We showed such strain propagation can be specifically targeted by aggregation-kinetic-informed machine learning pipelines. Finally, we show the unique strains of tau aggregate through unique kinetic landscapes. I advised a PhD student Alessia Santambrogio on the continuation of this work after my departure which has been one of the most rewarding experiences of my academic career. I further extended my technical repertoire with cryo-EM, biophyiscal and kinetic analysis of amyloid propagation, drug design and discovery, machine learning, and phase separation analysis.

Publications

2023

Horne, R. I.; Metrick, M. A. II; Man, W.; Rinauro, D. J.; Brotzakis, Z. F.; Chia, S.; Meisl, G.; Vendruscolo, M. Secondary Processes Dominate the Quiescent, Spontaneous Aggregation of a-Synuclein at Physiological pH with Sodium Salts. ACS Chem Neurosci. 2023

Koga, S.; Metrick, M. A. II; Golbe, L. I.; Santambrogio, A.; Kim, M.; Soto-Beasley, A. I.;Walton, R. L.; Baker, M. C.; De Castro, C. F.; DeTure, M.; Russell, D.; Navia, B. A.; Sandiego, C.; Ross, O. A.; Vendruscolo, M.; Caughey, B.; Dickson, D. W. Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration. Acta Neuropath. Comm. 2023

2022

Metrick, M. A. II. Amyloid seeding assays for the selective amplification of tau aggregates from human brain homogenates. University of Cambridge Thesis Repository. 2022

2021

Lin, J.; Figazzolo, C.; Metrick, M. A. II; Sormanni, P.; Vendruscolo, M. Computational maturation of a single-domain antibody against AB42 aggregation. Chemical Science. 2021

do Carmo Ferreira, N.; Charco, J. M.; Plagenz, J.; Orru, C. D.; Denkers, N. D.; Metrick II., M. A.; Hughson, A. G.; Griffin, K. A.; Race, B.; Hoover, E. A.; Castilla, J.; Nichols, T. A.; Miller, M. W.; Caughey, B. Detection of chronic wasting disease in mule and white-tailed deer by RT-QuIC analysis of outer ear. Sci. Rep. 2021

2020

Metrick II., M. A.; do Carmo Ferreira, N.; Kraus, A.; Saijo, E.; Ghetti, B.; Sigurdson, C.; Newell, K.; Zanusso, G.; Vendruscolo, M.; Caughey, B. A single ultrasensitive assay for detection and discrimination of tau aggregates of Alzheimer and Pick diseases. Acta Neuropath. Comm. 2020

2019

Saijo, E. † ; Metrick II., M. A. † ; Koga, S.; Parchi, P.; Litvan, I.; Spina, S.; Boxer, A.; Kraus, A.; Rossi, M.; Newell, K.; Zanusso, G.; Ghetti, B.; Dickson, D. W.; Caughey, B. 4-repeat tau seeds and templating subtypes as brain and CSF biomarkers for frontotemporal lobar degeneration. Acta Neuropath. 2019

Metrick II., M A.; Saijo, E.; do Carmo Ferreira, N.; Hughson, A.; Kraus, A.; Orrú, C.; Litvan, I.; Miller, M.W.; Zanusso, G.; Ghetti, B.; Vendruscolo, M.; Caughey, B. Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens using Hofmeister ion comparisons. PNAS. 2019

Kraus, A. † ; Saijo, E. † ; Metrick II., M. A. † ; Newell, K.; Sigurdson, C. J.; Zanusso, G.; Ghetti, B.; Caughey, B. Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease. Acta Neuropath. 2019

2016

Light, T. P.; Corbett, K. M.; Metrick, M. A.; MacDonald, G. Hofmeister Ion-induced changes in water structure correlate with changes in solvation of an aggregated protein complex. Langmuir. 2016

2015

Metrick, M. A.; MacDonald, G. Hofmeister ion effects on the solvation and thermal stability of model proteins lysozyme and myoglobin. Colloids and Surfaces A. 2015

Ma, J.; Metrick, M. A.; Ghirlando, R.; Zhao, H.; Schuck, P. Variable-Field Analytical Ultracentrifugation: I. Time-Optimized Sedimentation Equilibrium. Biophysical Journal. 2015, 109(4), 827-37

2013

Metrick, M. A.; Temple, J. E.; MacDonald, G. The effects of buffers and pH on the thermal stability, unfolding and substrate binding of RecA. Biophys. Chem. 2013, 184 , 29-36.

Patents

Methods for the detection of tau protein aggregates, US patent No. 11906530 Abstract: Methods are disclosed herein for determining whether a subject has a Tauopathy, such as Pick disease, Alzheimer disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) or argyrophilic grain disease (AGD). These methods utilize a seeding assay. Filed: December 2017; Awarded: February 2024

Chapters

Saijo E, Groveman BR, Kraus A, Metrick M. A., Orru CD, Hughson AG and B Caughey. Ultrasensitive RT-QuIC seed amplification assays for disease-associated tau, α-synuclein, and prion aggregates. Methods in Molecular Biology: Protein Misfolding Diseases (Springer) (Gomes, C, ed). 2018.

Technical Skills

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  • protein expression & purification

    • plasmid and construct design

    • transformation, colony enumeration

    • PCR, construct QC, RT-qPCR

    • expression, extraction

    • affinity, size exclusion chromatography

    • purity verification, protein QC, mass spectrometry

    • lyophilization and storage

    • SDS-PAGE, western blotting

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  • spectroscopy, microscopy, & protein characterization

    • ATR-FTIR spectrocopy, difference FTIR spectroscopy, H-D exchange FTIR spectroscopy

    • CD spectroscopy, thermal stability

    • TEM microscopy

    • cryo-EM sample preparation

    • confocal microscopy

    • fluorescence microscopy

    • reaction and aggregation kinetics

    • analytical ultracentrifugation

    • surface plasmon resonance

    • titration calorimetry

    • differential light scattering

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  • small molecules & drug development

    • small molecule docking site identification

    • molecule library generation

    • preparation, storage, quality control

    • assay design and validation

    • kinetic-informed machine learning

    • mechanism validation

    • binding thermodynamics and kinetics

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  • software & analysis

    • graphpad prism

    • omega MARS

    • imageJ

    • R

    • python

    • amyloFit

    • RELION

Teaching and Mentorship

Posters and conferences

Santambrogio, A.; Metrick, M. A. II; Lövenstam, S.; Horne, R.; Brotzakis, F.; Gallagher, N.; Rinauro, D.; Sakhnini, L.; Linse, S.; Caughey, B.; Scheres, S.; Vendruscolo, M. A Brain- Seeded Fibril Amplification Assay Models Tau Aggregation for Drug Discovery. Global Tau Conference, Washington D.C., March 2024

Geiser, R.; Sanguanini; M.; Staats, R.; Rinauro, D. J.; Metrick, M. A. II; Ciryam, P.; Casford, S.; Zhao, E.; Fleming, J.; Hunter, S.; Brayne, C.; Vendruscolo, M. Therapeutic drug targeting in Alzheimer disease. Annual Biophysical Society Meeting, San Francisco, CA, February 2022.

Man, W. K.; Metrick, M. A. II; Rinauro, D.; Vendruscolo, M. The aggregation kinetics of a- Synuclein at neutral pH under quiescent conditions. Annual Biophysical Society Meeting, San Francisco, CA, February 2022

do Carmo Ferreira, N.; Charco, J. M.; Metrick, M. A. II; Orru, C. D.; Hughson, A. G.; Castilla, J.; Miller, M. W.; Caughey, B. RT-QuIC as an antemortem diagnostic tool to detect chronic wasting disease in deer skin. Annual Prion Conference, Alberta, Canada, 2019

Temple, J., Metrick, M. A., MacDonald, G. Difference FT-IR Studies on the Effects of Buffers on Nucleotide Binding to RecA. 58th Annual Biophysical Society Meeting, San Francisco, CA, February 2014.

Light, T. P., Corbett, K. M., Metrick, M. A., MacDonald, G. Influence of Hofmeister Salts on the Structure, Aggregation, and Unfolding of RecA. 58th Annual Biophysical Society Meeting, San Francisco, CA, February 2014.

do Carmo Ferreira, N.; Charco, J. M.; Plagenz, J.; Orru, C. D.; Denkers, N. D.; Metrick II., M. A.; Hughson, A. G.; Griffin, K. A.; Race, B.; Hoover, E. A.; Castilla, J.; Nichols, T. A.; Miller, M. W.; Caughey, B. Detection of chronic wasting disease in mule and white-tailed deer by RT-QuIC analysis of outer ear. Sci. Rep. 2021

Metrick, M. A., MacDonald, G.. Spectroscopic studies of the influence of buffers and pH on the thermal stability, specific activity, and aggregation state of a naturally aggregating protein, RecA (Continuance). 57th Annual Biophysical Society Meeting, Philadelphia, PA, February 2013.

Metrick, M. A., MacDonald, G. Spectroscopic studies of the influence of buffers and pH on the thermal stability, specific activity, and aggregation state of a naturally aggregating protein, RecA. University of Maryland Baltimore County’s 17th annual Undergraduate Research Symposium, Baltimore, MD, October 2012.

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ResearchGate

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Profile

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Caughey lab

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Centre for Misfolding Diseases

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