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Harshad Ghodke, PhD

Hopkinton, MA
📧 hghodkephd@gmail.com
🔗 LinkedIn • Google Scholar • ORCID

Professional Summary

Scientist and engineering leader with 15+ years at the intersection of protein engineering, single-molecule biophysics, and high-throughput quantitative biology. I specialize in building data-rich, automation-enabled experimental platforms that accelerate AI-driven molecular design—linking mechanistic biochemistry, directed evolution, and structure–function analysis with machine-learning-ready datasets. My work focuses on generating clean, interpretable sequence-to-function data, partnering closely with computational groups to refine feature engineering, model training inputs, and validation strategies. I’ve led multidisciplinary teams to architect scalable workflows, reduce DBTL cycle times, and deliver IP-generating enzyme, biosensor, and analytical technologies. My academic and industry research has produced 30+ peer-reviewed publications, including Nature Communications, PNAS, eLife, NAR, and Angewandte Chemie.

PROFESSIONAL EXPERIENCE

Protein Evolution Inc., New Haven, CT (08/2022 – 01/2025)

Director of Enzyme Engineering (07/2024 – 01/2025)

  • Led scientific and strategic direction for enzyme engineering, guiding program design, prioritization, and mechanistic hypothesis generation across the organization.
  • Drove the development of a commercial-ready PET-depolymerizing enzyme in <14 months by integrating sequence–function modeling, structural reasoning, and data-driven variant prioritization.
  • Architected cross-functional workflows linking computational design, experimental validation, and bioprocess engineering (20+ collaborators), ensuring scientific alignment and clear technical decision-making.
  • Managed external partnerships (CROs, NSF/DOE funders), translating complex scientific goals into executable workstreams and maintaining trusted relationships with strategic stakeholders.

Principal Scientist (02/2024 – 01/2025)

  • Designed and launched the company’s full-stack protein engineering pipeline, enabling systematic exploration of high-dimensional sequence landscapes and rapid interpretation of structure–function trends.
  • Built scalable data and HT screening workflows combining microfluidics, automated 96/384-well assays, parallelized expression systems, and quantitative analytics for model-informed engineering.
  • Delivered enzymes with improved thermostability (>40 °C), aggregation resistance, pH tolerance, and manufacturability through integrated structural and high-throughput datasets.
  • Implemented Benchling-based LIMS and analytics tools enabling traceability, audit-ready IP documentation, and cross-team data integration.
  • Generated and analyzed >3,000 sequence–function datapoints, reducing DBTL cycle time and providing datasets for ML model calibration and validation.

Staff / Senior Scientist II (08/2022 – 01/2024)

  • Developed quantitative biophysical assays to assess folding stability, catalytic robustness, and environmental performance across discovery programs.
  • Used structure-guided mutagenesis (surface charge modulation, disulfide engineering, hydrophobic packing, loop stabilization) to interrogate mechanistic hypotheses and modulate activity.
  • Built Python-based analytic tools for real-time screening, curve fitting, QC, and automated data ingestion to accelerate decision-making.
  • Collaborated closely with process development, data science, and fermentation teams to ensure cohesive mechanistic interpretation and seamless assay execution.

Quantum-Si & University of Wollongong, Australia

Industry-Funded Consultant | Research Fellow (06/2021 – 06/2022)

  • Conceptualized and validated three single-molecule biosensing architectures by integrating PyMOL-based structural analysis, MD-informed reasoning, and quantitative biophysical screening.
  • Built a gene-to-glass CFPS workflow enabling <24 hr development of antibody fragments, site-specific conjugation, and scalable purification optimized for 384-well single-molecule assays.
  • Established integrated computational–experimental design cycles connecting structure prediction, feature extraction, and empirical optimization.
  • Mentored a team of 5 postdocs across expression engineering, assay development, and biophysical analytics.
  • Co-inventor on WO 2025/054427 A1 for novel fluorescent biosensor designs.

Molecular Horizons Institute, University of Wollongong — Research Fellow (2015 – 2022)

  • Led an independent research program dissecting genome-maintenance machinery using single-molecule imaging, structural biology, protein engineering, and quantitative mechanistic modeling.
  • Characterized key steps in DNA repair, replication, and recombination pathways (e.g., RecA filament dynamics during the SOS response; Mfd–UvrAB handoff during transcription-coupled repair).
  • Engineered fusion proteins and fluorescent constructs (e.g., dCas9–dL5), established scalable multi-step purification pipelines, and optimized construct stability and expression.
  • Performed quantitative biophysical analyses (SPR, fluorescence kinetics, binding lifetimes, single-molecule reaction trajectories). Developed the “interval imaging” kinetic method for distinguishing multi-population lifetimes.
  • Conducted targeted mutational analyses informed by structural and domain-level models to probe ATPase activity, DNA-binding energetics, and allosteric regulation.
  • Secured >$5M in competitive funding, supervised 4 PhD and 16 undergraduate researchers, and authored 25 peer-reviewed papers (8 senior author), demonstrating strong mentorship and scientific leadership.

SKILLS

Mechanistic Modeling & Biophysics

Protein–protein and protein–DNA interactions • Enzyme mechanism analysis • Oligonucleotide and nucleic acid engineering • Multi-population kinetic modeling • Conformational and stability assessment • PyMOL & ChimeraX

Quantitative Data Analysis & Computational Tools

Python (NumPy, SciPy, Pandas, Matplotlib; custom kinetic/curve-fit libraries) • MATLAB (ODE modeling, reaction networks) • Statistical QC • Workflow automation • Data ingestion and visualization pipelines

Biophysical Characterization

SPR (kon/koff/KD) • Fluorescence binding and reaction kinetics • Thermal/chemical stability profiling • Single-molecule imaging (TIRF, smFRET) • Quantitative assay performance evaluation

Protein, Enzyme & Biologic Engineering

Structure-guided mutagenesis • VHH/scFv design • Directed evolution • Rational stability/activity engineering • CFPS optimization • Conjugation chemistry • QC-ready reagent production

High-Throughput & Automated Workflows

Droplet microfluidics • 96/384-well assay miniaturization • Automated liquid handling • Parallel expression & purification workflows • High-throughput reaction monitoring • Data integration and pipeline orchestration

Data Infrastructure & Traceability

Benchling LIMS (construct metadata, lineage, assay integration) • Automated data capture • QC-annotated workflows • Audit-ready experiment documentation

Scientific Communication & Leadership

Interdisciplinary mentoring • Cross-functional collaboration (AI/ML, hardware, wet lab, bioinformatics) • Scientific writing (manuscripts, grants, patents) • Technical presentations • Strategy alignment and scientific roadmapping

EDUCATION

Ph.D. — Molecular Biophysics & Structural Biology
University of Pittsburgh & Carnegie Mellon University

M.S. — Chemical Engineering
Carnegie Mellon University

B.Tech — Chemical Engineering
Indian Institute of Technology Bombay

SELECTED PRESENTATIONS

  • Oral presentation, Lorne Proteins (2021): Single-molecule studies of transcription-coupled DNA repair
  • Travel award + invited talk, Fusion DNA Conference, Nassau (2020): Single-molecule studies of transcription-coupled DNA repair

INTERESTS

Ceramics • Bonsai • Landscape Photography
Founder — Ginkgo Clayworks

Peer-Reviewed Research Articles

2025

Cater, J.H., El Salamouni, N.S., Mansour, G.H., Hutchinson, S., McGuinness, C., … Ghodke, H.
Optimised nanobody-based quenchbodies for enhanced protein detection.
Communications Biology (2025) 8:937.
PMID: 40533519

2024

Xu, Z.Q., Jergic, S., Lo, A.T.Y., Pradhan, A.C., Brown, S.H.J., Bouwer, J.C., … Ghodke, H.
Structural characterisation of the complete cycle of sliding clamp loading in Escherichia coli.
Nature Communications 15:8372 (2024).

2023

Whinn, K.S., Xu, Z.Q., Jergic, S., Sharma, N., Spenkelink, L.M., Dixon, N.E., … Ghodke, H.
Single-molecule visualization of stalled replication-fork rescue by the E. coli Rep helicase.
Nucleic Acids Research 51(7):3307–3326 (2023).

Cherry, M.E., Dubiel, K., Henry, C., Wood, E.A., Revitt-Mills, S.A., Keck, J.L., … Ghodke, H.
Spatiotemporal dynamics of single-stranded DNA intermediates in Escherichia coli.
bioRxiv (2023).

Whinn, K.S., Sharma, N., van Oijen, A.M., Ghodke, H.
Single-Molecule Fluorescence Imaging of DNA Replication Stalling at Sites of Nucleoprotein Complexes.
In Single Molecule Analysis: Methods and Protocols, pp. 215–234 (2023).

2022

Paudel, B.P., Xu, Z.Q., Jergic, S., Oakley, A.J., Sharma, N., Brown, S.H.J., van Oijen, A.M., Ghodke, H., …
Mechanism of transcription modulation by the transcription-repair coupling factor.
Nucleic Acids Research 50(10):5688–5712 (2022).

Shaw, A.E., Kairamkonda, S., Ghodke, H., Schauer, G.D.
Biochemical and single-molecule techniques to study accessory helicase resolution of R-loop proteins.
Methods in Enzymology 673:191–225 (2022).

2021

Whinn, K.S., van Oijen, A.M., Ghodke, H.
Single-molecule studies of helicases and translocases in prokaryotic genome-maintenance pathways.
DNA Repair 108:103229 (2021).

2020

Ghodke, H., Ho, H.N., van Oijen, A.M.
Single-molecule live-cell imaging reveals parallel pathways of prokaryotic nucleotide excision repair.
Nature Communications 11:1477 (2020).

Ho, H.N., van Oijen, A.M., Ghodke, H.
Single-molecule imaging reveals molecular coupling between transcription and DNA repair machinery in live cells.
Nature Communications 11:1478 (2020).
PMID: 32198374

2019

Whinn, K.S., Kaur, G., Lewis, J.S., Schauer, G.D., Mueller, S.H., Jergic, S., … Ghodke, H.
Nuclease-dead Cas9 is a programmable roadblock for DNA replication.
Scientific Reports 9:13292 (2019).
PMID: 31477776

Ghodke, H., Paudel, B.P., Lewis, J.S., Jergic, S., Gopal, K., Romero, Z.J., Wood, E.A., …
Spatial and temporal organization of RecA in the E. coli DNA-damage response.
eLife 8:e42761 (2019).
PMID: 30717823

Henrikus, S.S., Henry, C., McGrath, A.E., Jergic, S., McDonald, J.P., Hellmich, Y., Wood, E.A., … Ghodke, H.
Single-molecule live-cell imaging reveals RecB-dependent function of DNA polymerase IV in double strand break repair.
Nucleic Acids Research 48(15):8490–8508 (2019).

Ho, H.N., Zalami, D., Köhler, J., van Oijen, A.M., Ghodke, H.
Identification of multiple kinetic populations of DNA-binding proteins in live cells.
Biophysical Journal 117(5):950–961 (2019).

2018

Ghodke, H., Ho, H.N., van Oijen, A.M.
Single-molecule live-cell imaging of bacterial DNA repair and damage tolerance.
Biochemical Society Transactions 46(1):23–35 (2018).

2016

Ghodke, H., Caldas, V.E.A., Punter, C.M., van Oijen, A.M., Robinson, A.
Single-molecule mislocalization of red fluorescent proteins in live Escherichia coli.
Biophysical Journal 111(1):25–27 (2016).

2015

Caldas, V.E.A., Punter, C.M., Ghodke, H., Robinson, A., van Oijen, A.M.
iSBatch: a batch-processing platform for data analysis and exploration of live-cell single-molecule microscopy datasets.
Molecular BioSystems 11(10):2699–2708 (2015).

Robinson, A., McDonald, J.P., Caldas, V.E.A., Patel, M., Wood, E.A., Punter, C.M., Ghodke, H., …
Regulation of mutagenic DNA polymerase V activation in space and time.
PLoS Genetics 11(8):e1005482 (2015).

2014

Ghodke, H., Wang, H., Hsieh, C.L., Woldemeskel, S., Watkins, S.C., Rapic-Otrin, V., Van Houten, B.
Single-molecule analysis reveals human UV-damaged DNA-binding protein (UV-DDB) dimerizes on DNA via multiple kinetic intermediates.
PNAS 111(18):E1862–E1871 (2014).
PMID: 24760829

Leuba, S.H., Carney, S.M., Dahlburg, E.M., Eells, R.J., Yanamala, N., Ghodke, H., …
Early integration of the individual student in academic activities: a novel classroom concept for graduate education.
BMC Biophysics 7:6 (2014).

2013

Hughes, C.D., Wang, H., Ghodke, H., Simons, M., Towheed, A., Peng, Y., …
Real-time single-molecule imaging reveals a direct interaction between UvrC and UvrB on DNA tightropes.
Nucleic Acids Research 41(9):4901–4912 (2013).

Godin, S., Wier, A., Kabbinavar, F., Bratton-Palmer, D., Ghodke, H., …
The Shu complex interacts with Rad51 through Rad55–Rad57 to mediate error-free recombination.
Nucleic Acids Research 41(8):4525–4534 (2013).

2011

Wang, H., Nora, G.J., Ghodke, H., Opresko, P.L.
Single-molecule studies of physiologically relevant telomeric tails reveal POT1 mechanism for promoting G-quadruplex unfolding.
Journal of Biological Chemistry 286(9):7479–7489 (2011).

2010

Keswani, R.K., Ghodke, H., Sarkar, D., Khilar, K.C., Srinivasa, R.S.
Room temperature synthesis of titanium dioxide nanoparticles of different phases in water-in-oil microemulsion.
Colloids and Surfaces A: Physicochemical and Engineering Aspects 369 (2010).

2007

Ghodke, H.B., Krishnan, R., Vignesh, K., Kumar, G.V.P., Narayana, C., Krishnan, Y.
The I-tetraplex building block: rational design and controlled fabrication of robust 1D DNA scaffolds through non-Watson–Crick interactions.
Angewandte Chemie International Edition 46(15):2646–2649 (2007).

Methods Chapters

2023

Whinn, K.S., Sharma, N., van Oijen, A.M., Ghodke, H.
Single-Molecule Fluorescence Imaging of DNA Replication Stalling at Sites of Nucleoprotein Complexes.
In Single Molecule Analysis: Methods and Protocols (2023), pp. 215–234.

2022

Shaw, A.E., Kairamkonda, S., Ghodke, H., Schauer, G.D.
Biochemical and single-molecule techniques to study accessory helicase resolution of R-loop proteins.
Methods in Enzymology 673:191–225 (2022).

Theses

2013

Ghodke, H.
Single molecule studies of damaged DNA recognition by the human UV-DDB protein.
Ph.D. Dissertation, University of Pittsburgh (2013).

2008

Ghodke, H.
Kinetic Modeling and Parameter Estimation of Semi-Batch, Free-Radical Polymerization.
M.S. Thesis, Carnegie Mellon University (2008).