Founder-scientist & molecular engineerXiaozhe (“XZ”) Ding 丁霄哲
Founder-scientist and molecular engineer building BBB shuttle technologies and AI-assisted discovery workflows for therapeutic delivery.
Co-founder and VP Technology at Receptive Bio. Work spanning protein engineering, receptor-mediated brain delivery, PK/PD reasoning, assay strategy, early CMC/developability, and AI-assisted discovery workflows.
Ph.D. in Bioengineering, minor in Computational Science and Engineering, Caltech · B.Sc. in Biological Science, Tsinghua University
BBB shuttle technologiesMolecular deliveryDecision-grade discovery workflowsAI-assisted protein and conjugate designFocus AreasWhat I build
BBB shuttle technologies
Receptor-mediated brain delivery, CA-IV-directed shuttle design, protein / biologics conjugation, and delivery strategy for CNS therapeutics.
AI-assisted discovery workflows
Structure-guided molecular design, APPRAISE, RFdiffusion / ProteinMPNN workflows, AlphaFold-style modeling, assay triage, and decision-grade experimental design.
Translational discovery systems
PK/PD reasoning, early CMC/developability considerations, assay credibility, vendor/CRO execution, and data-package readiness.
Selected ContributionsSelected non-confidential BBB shuttle technology contributions
Selected public and non-confidential contributions across BBB target discovery, shuttle design, conjugate strategy, and computationally guided proof-of-principle binder design.
BBB target discovery
Co-first / equal-contribution author. Science Advances study that helped establish CA-IV as a conserved BBB-crossing target. Contributed computational and structural analyses connecting brain-tropic AAV receptor usage to rational BBB shuttle design.
CA-IV shuttle design
Designed a CA-IV-directed small-molecule shuttle strategy for targeted brain delivery of biologics, connecting BBB target biology, chemical linker design, protein conjugation, and translational delivery strategy.
Translational conjugate design
Designed CA-IV shuttle-conjugates advancing therapeutic delivery of biologics across the BBB, with work spanning shuttle chemistry, cargo conjugation, assay strategy, PK/PD reasoning, and early developability considerations.
Mouse proof-of-principle BBB-crossing miniprotein
Designed and validated a BBB-crossing miniprotein proof of concept in mice using a mouse-species-specific BBB receptor. The workflow integrated RFdiffusion, ProteinMPNN, APPRAISE, AlphaFold-style structure modeling, cell-free expression, SPR / cell-based screening, and in vivo validation. Public patent filings disclose representative miniprotein binders from this workflow.
PublicationsSelected Publications, Patents & News
Selected publications and public filings most relevant to BBB shuttle design, computational protein engineering, and receptor-mediated therapeutic delivery.
Featured publicationsCA-IV-directed small-molecule shuttle enables targeted brain delivery of biologics
Nature Chemical Biology, accepted.
Role: First author and corresponding author.APPRAISE: Fast, accurate ranking of engineered proteins by receptor binding propensity using structural modeling
Molecular Therapy, 2024.
Role: First author and corresponding author.Primate-conserved Carbonic Anhydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier
Science Advances, 2023.
Role: Co-first / equal-contribution author.Additional publications, patents & newsHuman cell surface-AAV interactomes identify LRP6 as blood–brain-barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder
Nature Communications, 2024.
Functional gene delivery to and across brain vasculature of systemic AAVs
Nature Communications, 2023.
A modular, single-protein envelope for targeted gene delivery
Molecular Therapy Oncology, 2025 · sole-author commentary.
Structural basis of receptor usage by the engineered capsid AAV-PHP.eB
Molecular Therapy - Methods & Clinical Development, 2022.
CA-IV BBB target
Public filings covering CA-IV as a BBB-associated target for receptor-mediated transport of therapeutic cargos.
CA-IV SM shuttle
Public filings covering CA-IV small-molecule shuttle compositions and methods for transport across the blood–brain barrier.
Designed BBB-crossing miniproteins
Designed and validated BBB-crossing miniproteins proof-of-principle in mice using the mouse-species-specific BBB receptor LY6A, combining state-of-the-art tools available at the time, including RFdiffusion, ProteinMPNN, APPRAISE, AlphaFold-style confidence/structure modeling, cell-free expression, SPR/cell-based screening, and in vivo validation.
News & coverage
Selected institutional coverage of BBB-vector mechanisms, APPRAISE, AAV interactomes, and PHP.eB receptor usage.
Research archiveResearch archive
Detailed archive of selected research projects from Caltech, Tsinghua, Stanford, and related collaborations. For a concise summary of current technology contributions, see the section above.
APPRAISE: structural ranking for engineered protein binders
APPRAISE is an open-source framework for ranking engineered protein binders by predicted receptor-binding propensity using competitive structural modeling. The work connects structure modeling, protein engineering, and experimental triage for faster binder-design decisions.
BBB receptor discovery and AAV vector mechanisms
Ph.D. advisor: Viviana Gradinaru (Caltech). During my Ph.D., I developed and applied computational pipelines, including AlphaFold-style structural modeling, to help explain how engineered AAV vectors cross the blood–brain barrier and identify receptor mechanisms that inform next-generation delivery-vector design.
Earlier AAV capsid engineering and biophysics
Ph.D. advisor: Viviana Gradinaru (Caltech). Contributed to AAV capsid engineering projects spanning directed evolution, biodistribution, receptor mechanism, structural biology, and quantitative biophysical characterization.
Rotation projects
Caltech rotations with Frances H. Arnold (Nobel Prize in Chemistry, 2018), James R. Heath, and Mikhail G. Shapiro (HHMI Investigator): SCHEMA channelrhodopsin engineering, neoantigen T-cell detection, and acoustic modulation / biomolecular engineering.
Undergraduate research projects
Ratiometric calcium-indicator work generated early proof-of-concept data and received the Best Research Award in the Tsinghua Xuetang program. Earlier projects also included chemical-biology reviews, screening 87 voltage-sensor variants at Stanford with promising 50–100% larger fluorescence responses, and Spindlin1 histone-reader structural biology / ITC / mutant studies.
Side ProjectsSide Projects
Selected public tools and science-communication projects adjacent to my core molecular engineering work.
GPT Pull-down: AI-assisted protein interaction hypothesis generation
An early generative-AI prototype for molecular biology ideation, using LLMs to brainstorm candidate protein-interaction hypotheses and support literature-guided exploration.
Kerckhoff Outlook / 科考夫瞭望
Chinese-language science communication platform co-founded/co-edited during Caltech years.
ContactContact
For scientific, entrepreneurial, and collaboration inquiries, please reach out by email or LinkedIn.
BlogBlog
Personal writing on biotech entrepreneurship, scientific training, public science communication, and the transition from academic research to startup-building.
Ding Says / 老丁说
Personal writing on biotech entrepreneurship and scientific training.
Biotech Entrepreneurship Year Two
Reflections in an Age of Uncertainty.
From the Ivory Tower to Startups
The gains and losses of PhD-to-entrepreneurship.
Rewiring the Exam Mindset
Adapting from training systems to real-world ambiguity.
Ding Says archive · 24 posts
A compact index of existing Ding Says posts, linked directly to individual post URLs so the archive remains accessible even if the native Strikingly blog index is hidden or later moved.
Audible五年听书体会及个人五星/一星书单 / Five Years with Audible: Lessons Learned and My Five-Star and One-Star Lists2022English本泽传奇：我要一直走在最前沿，直到头发斑白、慢慢老去 / Seymour Benzer: Always at the Frontier, Until His Hair Turned Gray2018English二十世纪的费曼与二十一世纪的科学 |（《科考夫瞭望》创刊号） / Feynman in the Twentieth Century, Life Science in the Twenty-First2018English创业“二年级”笔记：在“乱纪元”中生长 / Biotech Entrepreneurship, Year Two: Growing Through an Era of Uncertainty2025English敢问路在何方？路在脚下——从看劝退文说起 / Where Does the Road Lead? It Begins Beneath Our Feet: On Essays Discouraging Life-Science Careers2013English
