Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 13th European Pathology Congress Milan, Italy.

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Day 2 :

  • Microbial Pathology | Breast Pathology | Dermatopathology | Veterinary pathology | Digital Pathology | | Plant pathology | Immunopathology | Histopathology | Speech & language pathology | Experimental Pathology

Session Introduction

Anita Huttner

Associate Professor of Pathology, Yale University School of Medicine, USA

Title: Recapitulating malformations of cortical development via Induced pluripotent stem cell technology

MD University of Erlangen-Nurnberg, Germany (1998)
Clinical Fellow Yale Medical School - Yale New Haven Hospital
Clinical Fellow Harvard Medical School - Brigham and Women's Hospital and Childrens' Hospital
Resident Yale Medical School - Yale New Haven Hospital
Resident Yale Medical School - Yale New Haven Hospital
Pre-/Postdoctoral fellow National Institutes of Health
Board Certification AB of Pathology, Anatomic Pathology (2012, recertified: 2015)
Board Certification AB of Pathology, Neuropathology (2015)



Background: Progress in our understanding of somatic cell reprogramming, particularly the isolation and characterization of human induced pluripotent stem cells (iPSCs) opened new avenues for modeling human disease.  IPSCs allow the generation of large numbers of genetically modifiable cells specific to the underlying human genetic background, and form an unparalleled opportunity to gain new insight into disease pathophysiology. This will further lay the foundation for the development of patient specific pharmacological assays and/or stem cell based therapies.  We focused on Walker Warburg Syndrome (WWS), a rare and severe form of lissencephaly paired with congenital muscular dystrophy.  Most children die before the age of three years. Several genes have been implicated in the etiology of this syndrome, however, to this date the pathogenesis is poorly understood. In addition, none of the animal models appears to faithfully reflect the human condition. Patient derived IPSCs, however, allow the targeted differentiation of cells into tissue specific phenotypes of brain and muscle, and thus provide an assay for the recapitulation of disease specific pathophysiology.

Design: IPSC lines were derived from skin biopsy specimens of patients with WWS and normal age matched controls. The generation of iPSCs followed established protocols using nucleofection (Amaxa system) of episomal plasmids expressing OCT3/4, SHp53, SOX2, KLF4, LIN28, and MYC.  The cells were grown in culture and differentiated into all lineages of the human brain. Furthermore, since one of the hallmark features of lissencephaly is altered neuronal activity, this system form a unique opportunity to monitor electrical activity of iPSC derived neurons.

Result: Directed differentiation of iPSCs into neuronal precursors was demonstrated in vitro with antibodies for CNS phenotypes, like GFAP, TUJ1, Tbr1/2.  Furthermore, neuronal activity was monitored with ultrasensitive fluorescent protein calcium sensors (GCaMP6) and showed altered neuronal activity in neurons derived from patients versus normal controls.

Conclusion: This model allows the phenotypic recapitulation of complex neurogenetic traits, and provides insights into the pathophysiology of human forms of malformations of cortical development. The combination of technologies offers a unique opportunity to model human neurological disease and hold promise for the development of new treatment this recognition.