Postdoctoral Research Associate - Gene Regulation, Single-Cell Multi-omics, and Functional Genomics

The Cheng Lab e Children's Research Hospital is seeking a highly motivated Postdoctoral Research Associate to investigate fundamental mechanisms of gene regulation and genetic variation in human hematopoiesis and blood disorders.

Our laboratory integrates single-cell multi-omics, functional genomics, human genetics, computational biology, and genetic/epigenetic perturbation to understand how cis-regulatory elements (CREs) control gene expression and how genetic variation in these elements contributes to human phenotypes and disease.

Using hematopoiesis as a model system, we study the dynamic organization and function of enhancers, silencers, insulators, and other CREs. Our research addresses three central questions:

• How are CREs spatially and temporally organized across cell types and developmental stages?
• How do common and rare genetic variants in CREs affect hematopoiesis and blood disorders?
• How can CREs be manipulated to improve genetic therapies?

Our previous work has developed high-throughput approaches to map functional CREs regulating red blood cell traits and identified potential targets for therapeutic genome editing in sickle cell disease (SCD) and β-thalassemia. We also develop computational approaches to improve the efficacy and safety of genetic therapies.

The successful candidate will have flexibility to develop projects within the laboratory's broader research program. Potential directions include:

• Integrating single-cell transcriptomic, epigenomic, and multi-omic data to understand gene regulation and cellular heterogeneity.
• Determining how genetic and structural variation alters cis-regulatory architecture and gene expression.
• Defining regulatory networks and genotype-to-phenotype relationships through computational genomics.
• Functionally testing regulatory elements and genetic variants using CRISPR-based genetic and epigenetic perturbation.
• Translating discoveries in gene regulation into new strategies for genome editing and genetic therapies.

One major NIH-funded project investigates fetal hemoglobin (HbF) regulation in SCD as a model for understanding regulatory heterogeneity. We are integrating single-cell multi-omics, human genetics, chromatin profiling, whole-genome sequencing, and genome editing to determine how genetic and epigenetic variation shapes HbF expression at single-cell resolution and influences therapeutic response and disease severity.

We welcome candidates with a PhD, MD/PhD, or equivalent degree in genetics, genomics, computational biology, bioinformatics, molecular biology, systems biology, hematology, computer science, or related fields.

Candidates with computational, experimental, or hybrid backgrounds are encouraged to apply. Experience in single-cell genomics, gene regulation/chromatin biology, computational genomics, human genetics, functional genomics, genome editing, or machine learning for genomic data is particularly relevant.

Prior experience in sickle cell disease or erythroid biology is not required.

The Cheng Lab provides an interdisciplinary environment at the interface of gene regulation, functional genomics, human genetics, computational biology, and genome engineering, with access to the extensive scientific and technological resources e.

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Jude.

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