Job Description

The Cousin Lab at Mayo Clinic is seeking a postdoctoral fellow will contribute to a growing rare disease therapeutics program with an initial emphasis on POLR2A-related disorders. This work will also support broader efforts in the lab, including genetic forms of ALS and other monogenic neurologic conditions. Projects may include iPSC-derived neural models, variant-mechanism studies, RNA-targeted therapies, genome editing, sequencing-based biomarkers, and collaboration with Mayo Clinic precision medicine and N-of-1 therapeutic programs, core facilities, and external academic partners.

The Cousin Lab at Mayo Clinic develops mechanism-guided, gene-targeted therapeutic strategies for rare neurogenetic diseases. Our work integrates clinical genetics, patient-derived biospecimens, functional genomics, iPSC-based disease modeling, preclinical therapeutic testing, and clinical translation.

The fellow will lead experimental and analytical components of translational rare disease projects. The role includes developing and characterizing patient-derived and engineered cell models; defining variant effects and disease mechanisms; designing and evaluating RNA-targeted and gene-editing therapeutic strategies; and integrating functional, genomic, and clinical data to prioritize treatment approaches. The position involves substantial wet-lab research, quantitative data analysis, manuscript and grant preparation, and cross-disciplinary collaboration.

The fellow will join a collaborative Mayo Clinic environment with access to clinical expertise, core facilities, genomic and sequencing resources, translational infrastructure, and multi-institutional rare disease networks. This position offers the opportunity to develop an independent research niche at the interface of rare disease biology, human neural modeling, and targeted therapeutic development; publish first-author manuscripts; present at national and international meetings; and pursue external fellowship or career-development funding.

Key Responsibilities

• Disease Modeling & Assay Development: Develop and characterize patient-derived and engineered disease models, including fibroblasts, iPSCs, isogenic controls, iPSC-derived neural cell types, and organoid or multicellular systems.

• Mechanistic & Functional Studies: Design and execute molecular, cellular, imaging, electrophysiologic, and functional genomics assays to define variant effects, disease mechanisms, cellular phenotypes, biomarkers, and therapeutic response.

• Therapeutic Development: Develop and evaluate RNA-targeted and gene-editing strategies, including ASO/siRNA, allele-selective or splice-modifying approaches, CRISPR/base-editing platforms, delivery systems, and target-engagement or rescue assays.

• Genomic Data Integration: Integrate variant interpretation, sequencing data, and functional readouts to prioritize therapeutic strategies and evaluate loss-of-function, dominant-negative, allele-specific, and related mechanisms.

• Collaboration & Translation: Coordinate with the PI, clinicians, partners, core facilities, biobanks, and external collaborators to align patient samples, disease models, assays, and preclinical workflows.

• Scientific Communication & Mentorship: Manage projects with rigor and reproducibility; prepare figures, reports, manuscripts, presentations, and grant/fellowship applications; and contribute to mentoring junior team members.

• Education: Ph.D., M.D./Ph.D., or equivalent doctoral degree in neuroscience, genetics/genomics, molecular or cell biology, stem cell biology, biomedical engineering, pharmacology, RNA biology, bioengineering, or a related field.

• Research Expertise: Demonstrated productivity in cell-based disease modeling, molecular biology, functional genomics, therapeutic development, neurogenetics, or rare disease biology.

• Technical Skills: Strong wet-lab skills in aseptic cell culture, molecular biology, assay development, sequencing workflows, microscopy/imaging, and experimental documentation.

• Quantitative & Analytical Skills: Ability to analyze, interpret, and communicate complex data; familiarity with Prism, R, Python, or related statistical and visualization tools is helpful.

• Professional Skills: Excellent organization, independence, attention to detail, and communication skills, with the ability to thrive in a collaborative translational research environment.

Experience in one or more of the following areas is preferred:

• iPSC & Neural Models: Experience with human iPSC culture, genome-edited/isogenic lines, neural differentiation, neurons, glia, organoids, or related iPSC-derived neural models.

• Therapeutic Platforms: Experience with RNA-targeted therapeutic development, genome engineering, or delivery platforms, including ASOs, siRNA, CRISPR/Cas, base or prime editing, AAV, or LNPs.

• Rare Disease Translation: Experience with rare genetic, neurodevelopmental, or neuromuscular disease models; patient-derived biospecimens; variant interpretation; genotype-phenotype analysis; or individualized/N-of-1 therapeutic approaches.

• Genomics & Biomarkers: Experience with RNA-seq, long-read sequencing, phasing/haplotype analysis, single-cell or multi-omic workflows, biomarker discovery, bioinformatics, or high-content/high-throughput screening.

• Scientific Leadership: Experience in translational or preclinical research, collaborative project management, manuscript preparation, grant writing, and mentoring.

Candidates should submit a CV, a brief cover letter describing research interests and relevant experience and contact information for 2-3 references.