Psychiatric & Neurodevelopmental Genetics Unit (PNGU)

The mission of PNGU is to identify and characterize the genetic basis of psychiatric, behavioral, and neurodevelopmental disorders and to translate these discoveries to improvements in clinical care and public health.

Amar SahayAmar Sahay, Ph.D. Principal Faculty, Harvard Stem Cell Institute
Assistant Professor, Center for Regenerative Medicine
Psychiatric and Neurodevelopmental Genetics Unit
Center for Human Genetic Research
Massachusetts General Hospital
Richard B. Simches Research Center
185 Cambridge Street
Boston, MA 02114
Phone: 617-643-4371 (o)
617-724-4978 (lab)
Email: sahay.amar@mgh.harvard.edu


Dr. Sahay is an Assistant Professor at the Center for Regenerative Medicine and the Department of Psychiatry at Massachusetts General Hospital, Harvard Medical School. He is also principal faculty of the Harvard Stem Cell Institute of Harvard University. The focus of Dr. Sahay’s research interests lies in understanding how stem cells in the adult brain may be harnessed to improve cognition and mood and how alterations in neural circuits contribute to the development of psychiatric disorders. The goal of his research program is ultimately to develop new therapeutic strategies for treating cognitive and mood impairments seen in psychiatric disorders such as depression, post-traumatic disorder and during normal aging.

Dr. Sahay earned his undergraduate degree at Bennington College and his doctorate in neuroscience from the Johns Hopkins University School of Medicine. Dr. Sahay’s doctoral thesis in the laboratories of Dr. Alex Kolodkin and Dr. David Ginty investigated the role of specific axon guidance cues, secreted semaphorins, in shaping neuronal connectivity in the developing mouse forebrain and in modulation of synaptic transmission in the adult brain. Dr. Sahay carried out postdoctoral research with Dr. Rene Hen at the Center for Neurobiology and Behavior at Columbia University’s School of Physicians and Surgeons. His research demonstrated that selectively increasing adult hippocampal neurogenesis is sufficient to improve pattern separation, a mnemonic process essential for episodic memory formation and potentially, a circuit-based endophenotype in psychiatric illnesses (Sahay et al, Neuron 2011).

Projects:

  • Adult-born hippocampal neurons in cognition and affective behaviors
    Although the maturation of the mammalian brain is marked by the progressive restriction of cellular and neural plasticity, it is now widely recognized that the dentate gyrus sub region of the hippocampus is host to neurogenesis, the generation of functional neurons from neural stem cells, throughout life. Our research seeks to: (i) Characterize the regulatory mechanisms that control adult hippocampal neurogenesis, (ii) Identify molecular programs that define the properties and connectivity of new neurons and link them with specific mnemonic processes (iii) Interrogate how stem cells and adult-born neurons function within the hippocampal circuit to influence learning and affective behaviors.
  • Neural mechanisms underlying psychiatric illnesses
    Most, if not all, psychiatric illnesses have their origins in the disruption of genetic and epigenetic programs that dictate embryonic and early-post natal development of neural circuits. We want to understand how alterations in neural circuits during the early postnatal period, when environment refines behaviors, contribute to perturbed affective behaviors and impairments in cognitive functions in adulthood.

    Towards these goals, we employ a combination of viral and mouse genetic based molecular-, pharmaco- and opto-genetic techniques to manipulate neural stem cells and distinct cell types, as well as candidate genes that we have identified, with concomitant assessment of circuit function and behavior. It is hoped that our efforts will shed light on: (i) The therapeutic potential of targeting adult neurogenesis for treatment of cognitive impairments and mood dysfunction, (ii) The identification of latent mechanisms of plasticity extant in other regions of the adult mammalian brain, and (iii) Etiological mechanisms underlying psychiatric illnesses.

Select Publications:

  • Amar Sahay*, Kimberly N. Scobie, Alexis S. Hill, Colin M. O'Carroll, Mazen A. Kheirbek, Nesha S. Burghardt, André A. Fenton, Alex Dranovsky and René Hen* (2011). Nature, April 28; 472 (7344): 466-70. * Co-corresponding author.  Covered in Leading edge, Cell 145, May 13, 2011.  Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.
  • Amar Sahay, Donald A. Wilson and René Hen (2011), Perspective, Special Issue: Reviews on stem cells and adult neurogenesis, Neuron, May 26, 70 (4), 582-588.  Pattern separation: A common function for new neurons in hippocampus and olfactory Bulb.
  • Kimberly N. Scobie, Benjamin J. Hall, Scott A. Wilke, Kristen C. Klemenhagen, Yoshiaki Fujii-Kuriyama, Anirvan Ghosh, René Hen and Amar Sahay (2009). The Journal of Neuroscience August 5; 29(31): 9875-9887.  Krüppel-like factor 9 (Klf-9) is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis (Cover Image)
  • Amar Sahay* and René Hen (2007), Focus on Emotion and Disorders of Emotion issue.  Nature Neuroscience 10(9):1110-1115. * Co-corresponding author. Adult hippocampal neurogenesis in depression
  • Amar Sahay, René Hen and Ronald S. Duman (2007). Adult Neurogenesis Cold Spring Harbor Monographs.  Chapter: Hippocampal neurogenesis: Depression and Antidepressant responses.
  • Amar Sahay *, Chong-Hyun Kim *, Edward Cho, Jehuda Sepkuty, Richard L. Huganir, David D. Ginty and Alex L. Kolodkin (2005). The Journal of Neuroscience Apr 6; 25(14): 3613-20.  Secreted semaphorins modulate synaptic transmission in the adult hippocampus (* equal contribution)
  • Amar Sahay, Mark E. Molliver, David D. Ginty and Alex L. Kolodkin (2003). The Journal of Neuroscience Jul 30; 23(17): 6671-80.  Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events.


See a complete list of Dr. Sahay's publications

Staff:

Lab manager
Sally Levinson, B.S (Ph.D. program in Neuroscience at NYU, 2013-)
Tomer Langberg, B.S. (2013- )

Research fellows
Nannan Guo, Ph.D. (Fudan University)
Kathleen McAvoy, Ph.D. (University of Rochester)
Antoine Besnard, Ph.D. (INSERM/CNRS/UPMC, Paris)

Graduate students
Tara Raam (Program in Neuroscience)
Hugo Vega-Ramirez (Program in Neuroscience)

Undergraduate students
Shannen Kim (Harvard)
Melissa Boldridge (Harvard)
Sekinat Jumai Yusuf (Harvard)

 

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