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.

Position Overview

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.