Lecture – The Alfred Pope Award for Early Career Investigators 2020

Available with English captions.

Honoring Maria Ironside, DPhil, and Bin Song, PhD, McLean Hospital

Approach-Avoidance Conflict in Major Depressive Disorder: Congruent Neural Findings in Humans and Nonhuman Primates

Maladaptive approach-avoidance behavior has been implicated in the pathophysiology of major depressive disorder (MDD), but the neural basis of these abnormalities in decision-making remains unclear. Capitalizing on recent preclinical findings, in a recent study Ironside and colleagues adapted an approach-avoidance conflict task from nonhuman primate research for use in human functional magnetic resonance imaging (fMRI).

In this presentation, Ironside:

  • Describes an overview of how approach avoidance conflict features in psychopathology
  • Explains how cross-species investigations are relevant to treatment development
  • Discusses the brain regions that are implicated in approach-avoidance conflict

Human Autologous iPSC-Derived Dopaminergic Progenitors Restore Motor Function in Parkinson’s Disease Models

Parkinson’s disease (PD) progression is driven by the irreversible degeneration of dopaminergic neurons of the basal ganglia. Transplantation of replacement dopamine cells for those lost to the disease has the potential to restore motor function and improve quality of life in PD patients. A promising strategy for this requires successful induction and differentiation of human-derived cells as well as patient tolerance to the graft. In a recent study, Song and colleagues established methods for efficiently producing clinical grade hiPSCs from patient’s dermal fibroblasts, optimizing differentiation to increase yield of healthy dopamine cells, and for eliminating undifferentiated cells with neoplastic potential. In animal models of PD, transplanting these hiPSC-derived dopamine cells successfully restored motor dysfunction without tumor formation, supporting the strategy’s viability for therapeutic development.

In this presentation, Song:

  • Describes an overview of cell therapy for Parkinson’s disease.
  • Explains why the critical step for cell therapy is safety, for example, how to remove the remaining undifferentiated cells
  • Discusses the advantage of autologous iPSC strategy for cell therapy