Senior Scientist I/II, In Vitro Pharmacology

Gordian Biotechnology•South San Francisco, CA

5d•$138,000 - $193,000•Onsite

About The Position

Gordian is hiring a Senior Scientist to build and lead in vitro pharmacology work across its obesity, chronic kidney disease/diabetic kidney disease (CKD/DKD), and heart failure with preserved ejection fraction (HFpEF) programs. The role develops and validates biochemical, biophysical, and cell-based assays for novel targets, often where tool compounds, established assays, and complete pathway biology are unavailable. In partnership with medicinal chemists, the scientist designs screening cascades from hit identification through lead optimization, defines progression criteria, and supports 1–2 week design-make-test cycles. In collaboration with the ex vivo team, the scientist helps develop disease-relevant human models and establish target-engagement, mechanism-of-action, and efficacy readouts, benchmarking against standard-of-care drugs where appropriate. The scientist will perform hands-on assay development and execution in Gordian’s laboratory while also scoping, selecting, and managing CRO work. Responsibilities include assay transfer and bridging studies, setting data acceptance standards, investigating assay drift and discrepancies, and providing recommendations at target and program reviews. The role will establish the equipment, assays, and SOPs needed to build Gordian’s in vitro pharmacology capability. Approximately half the time is expected to be hands-on laboratory work, with the remainder focused on cascade design, CRO management, analysis, and communication. Early milestones include learning Gordian’s platform and program status, auditing current assays and CRO data, and planning an assay for a novel target. Within two months, the scientist is expected to develop and validate a novel-target assay, document it in a validation report and SOP, launch a CRO study, and agree on human-system readouts and proof-of-mechanism criteria. Within three months, the first program’s cascade and progression criteria should be agreed with Chemistry and Biology, with initial SAR data delivered to Chemistry. Within six months, the goal is to have at least two validated primary assays for novel targets, a full cascade running for at least one program with a 1–2 week turnaround, and disease-relevant human systems on track. Over time, the scientist will build in vitro data packages to advance targets through lead optimization and toward development candidates.

Requirements

Track record of success in high-agency work, creating momentum without waiting for direction.
Understanding of in vitro pharmacology from first principles, including affinity, potency, efficacy, and how assay conditions and biological context affect EC50 or IC50 values.
Ability to interpret competitive, allosteric, tight-binding, and time-dependent mechanisms, curve shapes, and potency across biochemical, cellular, and tissue systems.
Knowledge of assay signal-generation formats including TR-FRET/HTRF, AlphaLISA, luminescence, fluorescence polarization, SPR, radioligand binding, reporter assays, and high-content imaging.
Experience validating assays to statistical standards such as Z′ and MSR and recognizing compound artifacts such as aggregation, signal interference, and cytotoxicity.
Ph.D. in pharmacology, biochemistry, cell biology, physiology, or a related field, plus 5 or more years of industry small-molecule drug-discovery experience; alternatively, an M.S. with 10 or more years of directly relevant industry experience.
Experience designing or owning a screening cascade from hit identification through lead optimization or candidate nomination, in partnership with medicinal chemists on SAR.
Experience in cardiometabolic, renal, or cardiovascular drug discovery.
Experience developing assays from scratch for poorly characterized targets without tool compounds or established readouts, across target classes such as GPCRs, enzymes, nuclear receptors, and transporters.
Experience scoping and managing CRO studies, transferring assays with bridging data, and identifying and correcting external data-quality problems.
Rigorous data-analysis skills and experience documenting work for reproducibility.
Ability to explain assay measurements and limitations to multidisciplinary audiences and make clear recommendations.
Willingness to work hands-on in an onsite laboratory role.

Nice To Haves

Experience across more than one of kidney, cardiac, and metabolic biology.
Target-engagement and biophysical methods such as CETSA, NanoBRET, or SPR.
First-in-class target experience with no prior chemistry or tool compounds.
Lab automation, liquid handling, or high-content imaging experience.
Experience with advanced human cell models such as iPSC-derived cells, 3D cultures, organoids, engineered heart tissue, kidney organoids, or microphysiological systems.
Understanding of PK/PD and in vitro-to-in vivo translation in cardiorenal disease.
Partner- or business-development-facing experience presenting preclinical data.
Experience with GraphPad, Genedata, or Spotfire; Python or R experience is a plus.

Responsibilities

Design, develop, and validate biochemical, biophysical, and cell-based assays for novel targets.
Design screening cascades from hit identification through lead optimization, including primary, orthogonal, counter-screen, selectivity, functional, and mechanism-of-action assays.
Set progression criteria and support 1–2 week design-make-test cycles with medicinal chemists.
Work with the ex vivo team to develop disease-relevant human models and define target-engagement, mechanism-of-action, and efficacy readouts.
Benchmark results against standard-of-care drugs where appropriate.
Scope, select, and manage CRO studies for screening; transfer assays, conduct bridging studies, and set data acceptance criteria.
Investigate assay drift, reference-compound shifts, compound artifacts, and discrepancies between internal and CRO data by identifying root causes.
Analyze data and provide clear recommendations for target and program decisions, including whether to advance, pause, or stop a program.
Build Gordian’s in vitro pharmacology capability, including equipment, assays, and SOPs.
Document assay methods and results so other scientists can find, reproduce, and build on the work.
Communicate what assays measure and their limitations to chemists, biologists, and executives.