Expertise
Five domains, led by imaging. Under each one, the assays I have designed and run, phrased the way I would phrase them on a call.
Imaging and high-content science
I am an imaging scientist first, and I work the whole chain rather than one link of it: the optics, the probe, the plate, the segmentation and the statistics. A high-content result that does not hold up almost always broke at one of those links and then got written up as biology. I step in wherever the chain is weak, not only at the analysis. What follows is what I do at each link, and what I have built with it.
Optics and instrumentation
I have built microscopes and run them in academic and industrial settings, so I read an image as an optical result before I read it as a biological one. Widefield, spinning-disk confocal, TIRF, two-photon, super-resolution (dSTORM and SIM) and single-particle tracking, with custom acquisition and analysis scripts, and the automated high-content systems and plate handling that turn a method into a screen. When a phenotype is really a focus drift, a bleaching curve or an illumination gradient, this is the layer where it shows.
Probes and panels
I select fluorophores on their photophysics and the optics in the room rather than on the catalogue: brightness (extinction coefficient times quantum yield), photostability under the illumination dose the assay will really deliver, blinking and stochastic switching for dSTORM and single-molecule work, and Stokes shift, where a long-shift dye can free a channel in a crowded panel. I design multiplex panels around spectral overlap rather than around what is already in the freezer. I have designed ligand-conjugated and bioconjugated fluorescent probes, at Lawrence Berkeley National Lab and at Vanderbilt, to label neuronal proteins for single-molecule imaging.
Methodology
Fixed ICC and IF, live-cell imaging and dynamics, sample preparation, plate layout and edge effects, and the controls and normalization that decide whether a number carries meaning. I have run this from dishes and chambers through 24-, 96-, 384- and 1536-well plates, and the design changes at every step up in density.
Analysis
Segmentation and feature extraction, quantitative features, clustering and multivariate statistics, and machine-learning image-analysis pipelines written in MATLAB and Python. From the single-particle tracking side I also analyze diffusion, clustering and membrane dynamics. What you get back is a pipeline you can rerun on your own data, not a folder of numbers.
Phenotypic discovery and assays
Phenotypic screening and profiling is where the rest of the chain gets used, and it is the work that moved programs: high-content imaging in industry across many plate types and cell samples, in 2D and 3D, analysed so the result could carry a decision. The readouts I have built carry neuro and immunology programs: ASC speck counting, synaptic puncta quantification, neurite outgrowth and health, microglia and astrocyte morphology classification, fibril uptake and aggregation, micronuclei and nuclear condensation, and calcium imaging. Each of those was built to run as a screen rather than as a single figure.
A PhD dissertation and ten publications on single-molecule imaging and fluorescent probes; the high-content screening assay portfolio at PhenoVista, a CRO; the automated high-content assays, in 2D and 3D across many plate formats and cell types, and the machine-learning image-analysis pipelines I built in industry.
Human cell models
I design and review human cell models: iPSC neuron, astrocyte and microglia mono- and tri-culture, and primary neural cultures where they are the better answer. The disease-relevant work is mostly pre-formed fibril and proteopathic-seed paradigms, where the job is separating uptake from seeding from aggregation rather than reporting one number. Around that sit the toxicity and health readouts — viability and neurotoxicity panels, mitochondrial stress, micronuclei and nuclear condensation. The part clients actually buy is the QC gates: the explicit criteria that separate a disease phenotype from differentiation noise, written down before the screen runs.
Assay cascades and platforms
A cascade runs biochemical to functional to translational, with a decision at every tier, and it is built for the modality you have rather than the one the last company had. For antibodies that means cell-based binding and blocking, internalization, FcR binding, ADCC and CDC. For siRNA and ASO it means knockdown validation, uptake, and conjugate delivery in neural cells. For small molecules it means FLIPR, HTRF, fluorescence polarization and reporter assays feeding phenotypic readouts. The functional tier is where most programs are thin: ion-channel and transporter flux, MEA electrophysiology, calcium imaging, flow cytometry, phagocytosis, chemotaxis, neurite outgrowth and health, and synaptic density.
Translational and biomarker science
The translational tier is where a discovery assay has to become something a clinical team can build on. I build and review human whole-blood and PBMC assays, MSD, ELISA and Luminex biofluid biomarker panels, target-engagement and receptor-occupancy designs, phospho-flow, and ex vivo whole-blood stimulation assays for PK/PD modelling, each with a fit-for-purpose validation plan covering precision, stability and donor variability. On the biology side this is mostly inflammasome and NLRP3 readouts, glial activation-state profiling, and complement and synaptic pruning. I have built human whole-blood biomarker assays in industry, which is a different discipline from building the same readout in a cell line.
Program and partner leadership
I have been the lead biologist on a neuroimmunology program through hit-to-lead, and I contributed mechanism-of-action work to two programs that reached development-candidate nomination, one of which is now in Phase 1. That work is where target identification and championing, CRO design and oversight, and science for leadership and partner reviews stop being separate skills. I write the RFP, score the vendors, and then sit on the sponsor side of the weekly call; I have also sat on the CRO side of that same call, leading teams on phenotypic assay development across multiple client engagements. Scientific due diligence and BD support come out of the same habit: reading a data package for what it actually supports.
Assay-family key
These four codes tag every offer on this site, so you can see at a glance which families an engagement touches.
- NF Neuronal function
- Neurite outgrowth and neurite health; ion-channel and transporter flux; calcium imaging; MEA electrophysiology (network activity, burst analysis); synapse density (puncta quantification), synaptogenesis, synapse loss
- NDD Neurodegeneration and proteinopathy
- iPSC-derived NDD models including neuron/astrocyte/microglia tri-culture; PFF and proteopathic-seed assays (aggregation, seeding, uptake); viability and neurotoxicity panels (excitotoxicity, oxidative stress, apoptosis/caspase, LDH, ATP); mitochondrial stress; micronuclei and nuclear condensation
- NI Neuroimmunology and glia
- Neuroinflammation assays; NLRP3 and inflammasome readouts (ASC-speck imaging, IL-1β release, pyroptosis, caspase-1); microglia and astrocyte activation-state profiling (cytokine panels, morphology classification, DAM and reactive-astrocyte markers); complement and synaptic pruning (C1q/C3 deposition, microglial engulfment); phagocytosis; chemotaxis (Boyden chamber)
- IT Immunology and translational
- Human whole-blood and PBMC assays; reporter assays; biofluid biomarker assays (MSD, ELISA); target-engagement and PD biomarker assays (receptor occupancy, phospho-flow, ex vivo whole-blood stimulation for PK/PD); antibody functional assays (ADCC, CDC, internalization, FcR binding, cell-based binding and blocking); siRNA and ASO knockdown and delivery (knockdown validation, uptake, conjugate delivery in neural cells)
Stated gaps
I do not claim these, and I will not learn them on your budget. I keep a short list of people who do this work and I refer without a fee, taking no commission, equity or consideration of any kind. Partner names go on this page once each of them has given written consent.
- Immunohistochemistry (IHC)
- Live-animal (in vivo) imaging
- Electron microscopy
Referred to partners.
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