Post Doctoral Fellow-MSH-30001-002

About the role

This project aims to develop and investigate human cortical brain organoids (hCBOs) derived from induced pluripotent stem cells (iPSCs) to elucidate molecular mechanisms and assess potential treatment strategies for PDHA1-related pyruvate dehydrogenase complex (PDHc) deficiency. The study will integrate structural, metabolic, and functional assessments to identify disease-related alterations and evaluate therapeutic interventions.

Responsibilities

• Months 7-9: Functional assessments will be conducted to investigate neuronal network activity. Multi-electrode array (MEA) recordings will evaluate extracellular neuronal firing patterns, burst frequency, and network synchronicity, while calcium imaging will assess intracellular neuronal excitability.
• Parallel metabolic analyses will begin, using metabolomic and proteomic profiling to determine how PDHA1 deficiency affects glycolysis, oxidative phosphorylation, and overall metabolic function of hCBOs.
• From months 10-12: Targeted therapeutic interventions will be introduced to determine their efficacy in restoring metabolic and functional deficits. Candidate treatments will include pyruvate supplementation, dichloroacetate (DCA), and alternative metabolic modulators to bypass PDHc dysfunction.
• The impact of these treatments will be evaluated by comparing structural, metabolic, and functional parameters between treated and untreated PDHA1-deficient organoids.
• Final multi-omic data integration will be performed to identify key molecular pathways involved in the disease and response to treatment.
• The final month will be dedicated to data analysis, manuscript preparation, and development of presentations for conferences and funding applications.

Qualifications

Prior clinical rotations in field of study, PhD in Genetics/Genomic Sciences from Icahn School of Medicine.