Stewart A Anderson, MD

faculty photo
Professor of Psychiatry
Department: Psychiatry
Graduate Group Affiliations

Contact information
3615 Civic Center Blvd.
Abramson Research Center
Room 517
Philadelphia, PA 19147
Office: 215-590-6527
Fax: 215-590-3709
BA (Neuroscience and Psychology)
Amherst College, Amherst, MA, 1984.
MD (Medicine)
University of Connecticut, Storrs, CT, 1989.
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Description of Research Expertise

I am a Children's Hospital of Philadelphia-based faculty in the Department of Psychiatry at UPenn.
The focus of my laboratory concerns the molecular and cellular mechanisms that govern the development of the mammalian forebrain. We use mouse genetics, forebrain slice and dissociated culture techniques, as well as mouse and human pluripotent stem cells in cell culture and transplantation experiments to study the fate determination of interneurons of the cerebral cortex. We are particularly interested in understanding the molecular underpinnings behind the fate determination of subclasses of GABAergic interneurons implicated in the neuropathology of autism and schizophrenia. In addition, we are using mouse and human stem cell-derived interneurons in animal models of cell-based therapies for seizures, psychosis, and as tools for the study of gene-gene and gene-environment interactions in neuropsychiatric disease.
Some Ongoing Projects:
1) Fate determination of cortical interneurons.
Example Hypothesis: Enhancement of subventricular zone-like symmetric divisions will enable the selective generation of fast-spiking, parvalbumin-expressing interneurons from mouse and human stem cells.
Translational implications. Use of stem cell derived cortical interneurons in cell based therapy for medication resistant epilepsy and psychosis.
2) Role of Mitochondria in cortical interneuron migration.
Collaborators Doug Wallace (CHOP/Penn), Jeffrey Golden (Harvard)
Hypothesis: Non-radial migration of cortical interneurons is far more dependent on oxidative phosphorylation than is radial migration of cortical projection neurons.
Translational implications. Genetic/environmental interaction in mitochondrial-related "interneuronopathies" such as epilepsy, learning disabilities, and autism-spectrum disorders, leading to novel prevention and treatment strategies.
3) Role of mitochondria dysfunction in schizophrenia.
Collaborators: Doug Wallace and Beverly Emanuel
Hypothesis. Forebrain-like excitatory projection neurons from Induced Pluriporent Stem Cells (IPSCs) from patients with schizophrenia and 22q11.2 deletion syndrome will have mitochondrial abnormalities that are correctable with antioxidants and other treatments.
Translational implications: Development of an efficient platform for drug screening, and a novel approach to understanding the complex interactions between nuclear and mitochondrial encoded genes in disorders of cortical function.
4) Role of the acetylcholine receptor AchR7 in cortical interneuron development.
Collaborator: David Lynch (CHOP/UPenn).
Hypothesis: Using Achr7 conditional mutant mice generated in the Anderson lab, we are studying the hypothesis that Achr7 signaling on fast-spiking interneurons is critical to their development of excitatory inputs via effects on serine racemase and NMDA receptor signaling.
Translational implications: Use of d-serine agonists to enhance cognition in selected subsets of people with schizophrenia.

Selected Publications

Tischfield DJ, Kim J, Anderson SA: Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells. Stem Cell Reports 8(5): 1135-43, 2017.

Tischfield DJ, Saraswat DK, Furash A, Fowler SC, Fuccillo MV, Anderson SA.: Loss of the neurodevelopmental gene Zswim6 alters striatal morphology and motor regulation. Neurobiology of Disease 103: 174-183, 2017.

Donegan JJ, Tyson JA, Branch SY, Beckstead MJ, Anderson SA, Lodge DJ.: Stem cell-derived interneuron transplants as a treatment for schizophrenia: preclinical validation in a rodent model. Mol Psychiatry. epub ahead of print, 2016.

Lin-Hendel EG, McManus MJ, Wallace DC, Anderson SA*, Golden JA*. (*co-corresponding authors): Differential mitochondrial requirements for radially and non-radially migrating cortical neurons: implications for mitochondrial disorders. Cell Reports in press, 2016.

Dimidschstein J, Chen Q, Tremblay R, Rogers SL, Saldi GA, Guo L, Xu Q, Liu R, Lu C, Chu J, Grimley JS, Krostag AR, Kaykas A, Avery MC, Rashid MS, Baek M, Jacob AL, Smith GB, Wilson DE, Kosche G, Kruglikov I, Rusielewicz T, Kotak VC, Mowery TM, Anderson SA, Callaway EM, Dasen JS, Fitzpatrick D, Fossati V, Long MA, Noggle S, Reynolds JH, Sanes DH, Rudy B, Feng G, Fishell G: A viral strategy for targeting and manipulating interneurons across vertebrate species. Nature Neuroscience 19(12): 1743-49, 2016.

Chu J, Anderson SA : Development of Cortical Interneurons. Neuropsychopharmacology 40(1): 16-23, 2015.

Jaiswal MK, Keros S, Zhao Z, Inan M, Schwartz TH, Anderson SA, Homanics GE, Goldstein PA : Reduction in focal ictal activity following transplantation of MGE interneurons requires expression of the GABAA receptor α4 subunit. Frontiers in Cellular Neuroscience 9: 127-134, 2015.

Lia D, Takedaa N, Jaina R, Manderfielda LJ, Liu F, Lia L, Anderson SA*, Epstein, J* (*co-corresponding authors): Hopx distinguishes hippocampal from lateral ventricle neural stem cells and regulates neurogenesis. Stem Cell Research 15(3): 522-9, 2015.

Anderson SA, Parent JM (2015). : Reprogramming patient-derived cells to study the epilepsies. Nature Neuroscience 18(3): 360-366, 2015.

Tyson JA, Goldberg EM, Maroof AM, Xu Q, Petros TJ, Anderson SA.: Duration of culture and Sonic Hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells. Development 142(7): 1267-78. 2015.

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Last updated: 05/16/2017
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