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Dr. Ronald Toth IV

Biophysicist, data scientist, and roboticist with 11 years of experience

Education

  • PhD in Physical Chemistry, 2012

    University of New Hampshire

  • BS in Biomathematics, 2007

    Rutgers University

  • BS in Biotechnology, 2007

    Rutgers University

Experience

7 Years Industry, 4 Years Academia

Publications

19

Citations

Over 200

Experience

 
 
 
 
 

Associate Director

Sanofi Genzyme | Genomic Medicine Unit | Characterization

Apr 2023 – Present Boston, MA

Programs in the Genomic Medicine Unit include viral vectors (e.g., AAV), non-viral vectors (e.g., lipid nanoparticle (LNP)), and cell therapies. My core responsibilities are to support these programs by building out our biophysical analysis capabilities by

  • developing and running deep characterization methods using techniques such as DLS, MALS, NTA, AF4, and SV-AUC,
  • researching existing and novel characterization strategies to bring in-house or outsource,
  • hiring scientists to fill out our biophysical characterization team.
 
 
 
 
 

Senior Scientist

Sanofi Genzyme | Genomic Medicine Unit | Characterization

Apr 2021 – Apr 2023 Boston, MA
 
 
 
 
 

Senior Scientist

Repertoire Immune Medicines | Cell Process Development

Jul 2020 – Apr 2021 Boston, MA

My work was split between formulation development for T-cell therapy products and data science including database development and management. In this role I

  • improved the viability of cells infused to patients by researching, testing, and implementing the use of novel cryoprotective agents and by optimizing controlled rate freezer cycles,
  • developed and implemented databases to store process development data and preserve organizational knowledge.
 
 
 
 
 

Scientist - Biophysics

GSK Vaccines

Jul 2017 – Present Rockville, MD

As a scientist in Drug Product, my core responsibilities are to

  • design and execute formulation development studies to supporting IND filings,
  • report and contextualize the results of studies in documents and slide decks, presenting the findings to the organization’s leadership boards,
  • serve on Drug Product development boards defining quality attributes and formulation control strategies based on technical risk assessments.

 

As the Lead Biophysical Scientist in Drug Product, I

  • use biophysical knowledge and expertise to overcome analytical and development challenges,
  • Serve as a subject matter expert for biophysical techniques, mentoring others in their use.

 

As a member of the High-Throughput and Automation work-stream, I

  • develop scripts on the TECAN (sample handling robotics platform) to automate experiments and sample preparation,
  • develop workflows and platform approaches to improve the efficiency of high-throughput analytical instruments.

 

During my tenure in Drug Product, I became interested in visual design, data science, and programming. To this end I

  • write applications in the R language to help colleagues automate common data analysis and statistical tasks (such as parsing and analyzing data from a PDF report, generating study designs based DoE models, and performing scale-up and scale-down calculations),
  • lead tutorials on how to use R (topics include graphing data, authoring document, and managing databases),
  • author document templates to help colleagues communicate their data in a visually cohesive manner.
 
 
 
 
 

Associate Researcher

MVSC - University of Kansas

Jun 2015 – Jul 2017 Lawrence, KS

PIs: David Weis (Weis Research Group Homepage), David Volkin, Russ Middaugh

In my role as an associate researcher, I led research projects focused on using Hydrogen Exchange Mass Spectrometry (HX-MS) for

  • monitoring of protein structure over time while adjuvanted to aluminum hydroxide,
  • development of equations to correct HX-MS data for chemical exchange rates differing between buffer conditions,
  • monitoring conformational dynamics of mAb during buffer and excipient screens,
  • epitope mapping of ricin toxin to guide vaccine design.

 

I also supervised and mentored graduate students whose projects involved HX-MS.

 
 
 
 
 

Postdoctoral Researcher

MVSC - University of Kansas

Jun 2013 – Jul 2015 Lawrence, KS

PIs: David Volkin, Russ Middaugh

My job as a postdoctoral researcher was to design and execute study packages purchased by pharmaceutical corporations outsourcing their development; these studies included excipient screens, formulation development packages, and characterization packages.

As the center’s expert in analytical ultracentrifugation, I was responsible for executing that portion of all work packages.

 
 
 
 
 

Research Assistant

CAMIS - University of New Hampshire

Aug 2008 – Jun 2013 Durham, NH

PI: Thomas Laue

My graduate thesis work centered around using analytical ultracentrifugation to

  • study nonspecific molecular interaction in high-concentration, non-ideal solutions (such as charge-charge, dipole moment, and Van der Waals interactions),
  • study specific interactions in non-ideal solutions (such as antibody binding stoichiometries and kinetics).

Core Competencies

Biophysical Analysis

  • Analytical Ultracentrifugation (AUC)
    • Sedimentation Velocity (SV)
    • Sedimentation Equilibrium (SE)
  • Surface Plasmon Resonance (SPR, Biacore)
  • Bio-Layer Interferometry (BLI, Octet)
  • Circular Dichroism (CD, Chirascan)
  • Fourier Transform InfraRed Spectroscopy (FTIR)
  • Dynamic Light Scattering (DLS)
  • Static Light Scattering (SLS)
  • Differential Scanning Calorimetry (DSC)
  • Differential Scanning Fluorimetry (DSF)
  • Intrinsic and extrinsic fluorescence

Mass Spectrometry

  • Hydrogen – Deuterium Exchange (HDX, HX-MS)
  • Peptide Mapping
  • Intact Mass

Liquid Handling Robotics

  • TECAN
  • Hamilton

Chemical and Charge Analysis

  • Capillary Electrophoresis (CE)
  • Capillary IsoElectric Focusing (cIEF)
  • Zeta Potential (Via Nanosight Tracking Analysis and ZetaView)

Particle Analysis

  • Nanosight Tracking Analysis (NTA)
  • Micro-Flow Imaging (MFI)
  • Archimedes

Chromatography

  • Size Exclusion Chromatography (SEC)
  • Reversed Phase (RP)
  • Ion Exchange Chromatography (IEC)
  • Hydrophobic Interaction Chromatography (HIC)

Data Analysis

  • JMP
  • OriginLab
  • Excel
    • Pivot tables
    • Power Pivot
    • Power Query
    • Visual Basic

Data Science and Programming

  • R (language for statistical computing)
  • JavaScript (language for visual design)
  • HTML (language for visual design)
  • Markdown (language for document typesetting)
  • LaTeX (language for document typesetting)

Scientific Contributions

Conference Presentations

A High-Throughput, Comprehensive Degradation Temperature Panel is Vital for AAV Development (watch here)

  • Nov 2023 | Gene Therapy Analytical Development (Plenary)

The Critical Role of First-Principles, Fundamental Techniques in Gene Therapy (watch here)

  • Mar 2023 | Gene Therapy Comparability Summit (Invited)
  • Sep 2022 | Viral Vector Characterization Summit (Invited)
  • Oct 2023 | Beckman AUC User’s Group Meeting (Invited)

Sedimentation Velocity Analytical Ultracentrifugation (SV-AUC) as an Important Orthogonal Tool for Gene Therapy Characterization (watch here)

  • Aug 2022 | 14th Annual Bioprocessing Summit (Invited)
  • Nov 2022 | Global BioProcessing Summit (Invited)
  • Nov 2022 | Gene Therapy Analytical Development (Plenary)
  • May 2023 | PEGS Boston (Invited)

First Author Publications

Evaluation of Hydrogen Exchange Mass Spectrometry as a Stability-Indicating Method for Formulation Excipient Screening for an IgG4 Monoclonal Antibody. J Pharm Sci. (2018), DOI.

Empirical Correction for Differences in Chemical Exchange Rates in Hydrogen Exchange-Mass Spectrometry Measurements. Analytical Chemistry (2017), DOI.

High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine. Clin Vaccine Immunol. (2017), DOI.

Nonideality in high concentration solutions. University of New Hampshire Doctoral Dissertations (2012), LINK.

Publications from Mentored Students

Characterization of Excipient Effects on Reversible Self-association, Backbone Flexibility, and Solution Properties of an IgG1 Monoclonal Antibody at High Concentrations: Part 2. J Pharm Sci. (2019), DOI.

Impact of Glycosylation on the Local Backbone Flexibility of Well-Defined IgG1-Fc Glycoforms Using Hydrogen Exchange-Mass Spectrometry. J Pharm Sci. (2018), DOI.

A Collection of Single-Domain Antibodies that Crowd Ricin Toxin’s Active Site. Antibodies (2018), DOI.

Collaborative Publications

Recombinant Subunit Rotavirus Trivalent Vaccine Candidate: Physicochemical Comparisons and Stability Evaluations of Three Protein Antigens. J Pharm Sci. (2020), DOI.

Fine-Specificity Epitope Analysis Identifies Contact Points on Ricin Toxin Recognized by Protective Monoclonal Antibodies. Immunohorizons (2018), DOI.

Structural Characterization and Physicochemical Stability Profile of a Double Mutant Heat Labile Toxin Protein Based Adjuvant. J Pharm Sci. (2017), DOI.

Using homology modeling to interrogate binding affinity in neutralization of ricin toxin by a family of single domain antibodies. Proteins (2017), DOI.

Effects of Protein Conformation, Apparent Solubility, and Protein-Protein Interactions on the Rates and Mechanisms of Aggregation for an IgG1Monoclonal Antibody. J Phys Chem B. (2016), DOI.

Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms. J Chromatogr B Analyt Technol Biomed Life Sci. (2016), DOI.

Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri. Protein Sci. (2016), DOI.

Site-Specific Hydrolysis Reaction C-Terminal of Methionine in Met-His during Metal-Catalyzed Oxidation of IgG-1. Mol Pharm. (2016), DOI.

Biophysical Characterization of the Type III Secretion System Translocator Proteins and the Translocator Proteins Attached to Bacterium-Like Particles. J Pharm Sci. (2015), DOI.

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation. PLoS One (2015), DOI.

Impact of detergent on biophysical properties and immune response of the IpaDB fusion protein, a candidate subunit vaccine against Shigella species. Infect Immun. (2015), DOI.

N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD. Biochemistry (2013), DOI.

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