Work Experience
Seagen (2020-2024)
Director of Quantitative Pharmacology and Disposition (2020-2024)
Manager, platform model development, translational modeling support, and team building
- Created workflows to automate the analysis and reporting of non-GLP studies.
- Developed junior scientists in a growing group: created and ran training sessions for R and modeling and simulation tools; provided mentorship and career guidance.
- Acted as a project team representative for preclinical programs.
- Provided modeling and simulation support for projects and platforms from discovery through development.
- Created validated NONMEM environment used by the quantitatively pharmacology group for regulatory submissions.
- Authored module 2.6.4 and study reports for IND submissions.
- Clinical pharmacology representative for early stage programs.
Amgen (2013-2020)
Preclinical Director, Discovery & Translational Sciences, PKDM, (2019-2020)
Principal Scientist, PKDM, San Francisco, Ca (2016-2019)
Manager, platform model development, and translational modeling support
- Managed direct reports.
- Responsible for module 2.6.4 in INDs for immune-oncology programs.
- Project team representative typically supporting 8-12 programs in oncology and metabolic disorders from early discovery through FIH.
- Supported product life-cycle management by evaluating feasibility of new indications and development of new molecules to support franchises.
- Developed modeling tools to guide determination of antibody design goals for Therapeutic Discovery.
- Automated analysis and reporting of common PKDM-related tasks (non-compartmental analysis, GLP-tox study design, etc.) run completely in free software (R) with web-based interfaces (Shiny).
- Created workshop in R focusing on software and analysis techniques in the context of preclinical drug development.
Senior Scientist, Medical Sciences (2013-2016)
Translational modeling support
- Provided the modeling support to combine indication specific parameters in non-human primates with human response to G-CSF to identify dosing regimens to support sBLAs for Acute Radiation Syndrome for Neupogen and Neulasta using the animal rule.
- Mentored new project representatives in PKDM and CPMS with a focus on developing preclinical programs to support clinical advancement.
- Managed and coordinated the outsourcing of project components to bring new knowledge and capabilities in house and make filing deadlines.
- Developed translational modeling and simulation strategies for FIH dose projections to identify drugability liabilities.
Pfizer (2010-2013)
Principal Scientist, Systems Pharmacology (2010-2013)
Pfizer Inc, Pharmacokinetics Dynamics and Metabolism (PDM), Andover/Cambridge (2010-2013)
Provide modeling support for drug candidates from early discovery through Phase I
- Incorporation of in vitro and in vivo data into systemic models of drug disposition and efficacy on indications spanning the Inflammatory & Autoimmunity, and Orphan & Genetic Diseases Research Units as well as the Centers for Therapeutic Innovation (Boston and La Jolla).
- Provided modeling and simulation support to 15 project teams including: experimental design for parameter identification; linking physiology and pharmacology to provide comparative analysis of competitor compounds (both approved and in development) to ensure differentiability; analysis of different strategies to guide project teams in deciding which modality, technology, etc. to employ. -Developed a model generation system allowing description of models with simple text files that could then be used to create models in several formats (Matlab, ADAPT, Monolix, Berkeley Madonna, etc.) this included: a deployable GUI to be used by project teams, PDM project representatives, and analytical scientists; facilitated the transfer of models to the Clinical Pharmacology group when the project moves forward; makes models available to others within PDM in languages they are familiar with.
- Created tools for bioanalytical scientists to promote assay development by quantifying aspects such as the effect of sample impurities on measurements, characterizing anti-drug antibody response, and the affinity and concentration of neutralizing antibodies.
- Participated in due diligence teams by evaluating preclinical and clinical data identifying risks associated with in- licensing and asset acquisition.
- Mentored interns, both within PDM and in the clinical pharmacology group, developing systems models to support projects in both early stage development as well as compounds currently in the clinic.
Center for Protein Therapeutics, Pharmaceutical Sciences Department, SUNY Buffalo (2008-2010)
Postdoctoral Fellow
Developed multi-scale PKPD models of combination therapy for monoclonal antibody systems
- Developed qualitative and quantitative models of signal transduction in B-cell lymphomas based on in vitro CD20 agonist data.
- Created mechanistic PKPD model of single agent efficacy in mice that when modulated by the signal transduction model was capable of predicting the synergistic effects of two different combination regimens.
- Mentored and trained graduate students in various aspects of modeling and simulation associated with PKPD systems.
US State Department, Peace Corps (2005-2007)
Peace Corps Volunteer in Samoa
Visiting lecturer in the Science Department at the National University of Samoa
Developed the curriculum for current courses in cellular and molecular biology, plant and animal physiology, and environmental chemistry.
Created new upper level physics courses in environmental physics and energy supplies which complemented the current program in environmental science and allowed the creation of physics minor.
Provided training and teaching material to secondary school biology teachers preparing highschool level students for regional qualifying exams.
University of Pittsburgh, Department of Chemical Engineering (2000-2005)
Doctoral Candidate, Advisor: Prof. Robert S. Parker
Model–Based Design of Cancer Chemotherapy Treatment Schedules
- Developed nonlinear pharmacokinetic and pharmacodynamic models of 9-Nitrocamptothecin in severe combined immunodeficient (SCID) mice bearing subcutaneously implanted HT29 human colon xenografts.
- Designed a control algorithm which balanced the need to reduce tumor burden and avoid toxic side effects without violating clinical constraints to provide clinically relevant cancer chemotherapy drug schedule.
- Ensured clinical relevance of results by interacting regularly with collaborators from several fields including clinical oncologists, animal pharmacologists, and technicians.
University of Arkansas, Fayetteville AR, Department of Chemical Engineering (1998-2000)
Graduate Student Researcher, Advisor: Prof. Robert R. Beitle
Using Optical Tweezers to Determine the Suitability of Chromatography Packing
- Created actuators by covalently anchoring proteins to the surface of chemically active microspheres.
- Designed a methodology to rapidly evaluate the suitability of chromatography packing while minimizing the amount of protein required for the evaluations.
- Methodology refined to minimize the economic costs associated with developing protein purification procedures for expensive therapeutic proteins.
Education
Ph.D., Chemical Engineering, University of Pittsburgh, Pittsburgh, PA August 2005
M.S., Chemical Engineering, University of Arkansas, Fayetteville, AR August 2000
B.S., Chemical Engineering, University of Arkansas, Fayetteville, AR August 1998
Tool Development
Develop and maintain the ubiquity modeling and simulation tools to support model development and deployment in heterogeneous environments (2014-present).
- Web: https://ubiquity.tools
- Publication: https://doi.org/10.1007/s10928-014-9352-6
- GitHub: https://github.com/john-harrold/ubiquity-pkpd
Maintain the {ubiqiuty} R package, a complete modeling and simulation workflow to support preclinical and translational drug development (2017-present).
- Web: https://r.ubiquity.tools
- CRAN: https://CRAN.R-project.org/package=ubiquity
- GitHub: https://github.com/john-harrold/ubiquity
Maintain the {onbrand} R package, Automated reporting in Word and PowerPoint can require customization for each organizational template (2020-present).
- Web: https://onbrand.ubiquity.tools
- CRAN: https://CRAN.R-project.org/package=onbrand
- GitHub: https://github.com/john-harrold/onbrand
Maintain the {nlmixr2rpt} R package, Generate reporting workflows around {nlmixr2} analyses with outputs in Word and PowerPoint (2020-present).
- Web: https://nlmixr2.github.io/nlmixr2rpt/
- CRAN: https://CRAN.R-project.org/package=nlmixr2rpt
- GitHub: https://github.com/john-harrold/nlmixr2rpt
Maintain the {ruminate} R package, A pharmacometrics data transformation and analysis tool (2022-present).
Maintain the {formods} R package, Set of Shiny modules for general tasks (2022-present).
Member of the {nlmixr2} development team.
Publications
- @liu_translational_2024
- @kondic_navigating_2022
- @selvaggio_computational_2022
- @pham_preclinical_2021
- @lu_gipr_2021
- @harrold_ars_human_2020
- @harrold_ars_nhp_2020
- @Melhem:2018ik
- @krzyzanski2016cell
- @Tiwari2016
- @Krzyzanski2015
- @Chudasama2015
- @harrold2014ubiquity
- @dwivedi2014
- @Harrold:2013CPT
- @Harrold:2012kp
- @Vugmeyster:2012bra
- @Chudasama:2012fb
- @Vugmeyster:2012br
- @Kagan:2010p34187
- @Zhou:2009p27511
- @Harrold:2009p26247
- @har06
- @har05
- @par04
Posters & Presentations
- @patilea-vrana_abstract_2023
- @andrews_abstract_2022
- @li_718_2020
- @bailis_abstract_2020
- @AAPSHarrold2019
- @ACOPma2016
- @NBCtawari2016
- @ASCPTma2016
- @ACOPHarrold2015
- @ACOPAbuqayyas2015
- @ACOPWu2015
- @ACOP2013
- @ACOP2011
- @mager2010mechanistic
- @ACOP2009
- @har04b
- @har04
- @har03b
- @har03
- @har02