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Highlighting Neuroscience Innovation
at Boston Children's Hospital


Boston Children's Research Showcase and Networking Reception:

Advancing the Development of Neurological Disease Therapies

Our esteemed panelists in discussion

In November, TIDO organized the second of three Boston Children’s Research Showcase and Networking Events hosted at MassBio Headquarters in Cambridge. The event, co-organized with the F.M. Kirby Neurobiology Center and the Translational Neuroscience Center, focused on advancing therapies for neurological disorders.

We heard excellent research talks from:

  • Zhigang He, on axon regeneration and neural repair

  • Beth Stevens, on immune mechanisms of synapse loss in health & disease.

  • Judith Steen, on the proteomics of neurodegeneration.

Posters were presented from the laboratories of:

The night featured a panel discussion between neuroscientists at Boston Children’s (Clifford Woolf - Director of the F.M. Kirby Neurobiology Center and Christopher Walsh - Chief of the Division of Genetics) and biotech companies (James Doherty - Chief Research Officer, Sage Therapeutics and Lamya Shihabuddin - Cluster Head, Neuro Rare Diseases, Sanofi), which you can read about it in Vector, the Boston Children's science and clinical innovation blog.

Our third research showcase event, where we will highlight gene therapy efforts at Boston Children’s, will take place on April 30th. You can find more information and register here


Opportunities for Partnership in Neuroscience:


Novel therapeutic target to treat nerve damage 

Zhigang He, PhD, BM and Thomas Schwarz, PhD, associates in Neurology and the Neurobiology Program, have determined that a mitochondrial protein, Armcx1, enhances retinal ganglion cell survival and regeneration by increasing mitochondrial transport in injured axons.

Their work, published in Neuron, reveals a novel target for therapeutic intervention to treat nerve damage and neurodegeneration.

Learn More...

(A) Average percentage of RGC survival as measured by Tuj1 staining. (B) whole-mount optic nerve from wild-type mice injected with AAV-PLAP or AAV-Armcx1 15 days after optic nerve crush (dashed red line).

Improved white matter imaging using a novel computational model

Simon Warfield, PhD (Director of the Computational Radiology Laboratory) and his group have developed a novel model that addresses limitations of MRI techniques for imaging brain microstructures. The technique, known as DIAMOND, provides higher resolution of tissue microstructures and reduction in imaging time.

DIAMOND may lead to novel biomarkers and investigation of white matter microstructures in normal and diseased brains.

Learn More...

We consider the mixing of an isotropic (red) and two anisotropic (blue and green) tissue compartments. Because the representation of the 6-dimensional tensor-variate distribution of DIAMOND is challenging, the left panel shows projection of the distribution for 2-D tensors. Bottom panel shows the corresponding density of probability representation in the space of tensors. DIAMOND models each family of 3-D spin packets with a peak-shaped distribution of 3-D diffusivities.

Chelation of zinc promotes nerve regeneration

Larry Benowitz, PhD (Director, Laboratories for Neuroscience Research in Neurosurgery) and Paul Rosenberg, MD, PhD (Senior Associate in Neurology) have discovered that there is a rapid elevation of free zinc in the retina after optic nerve injury and that mitigating this elevation zinc chelation promotes regeneration of injured axons.

These findings can be applied therapeutically to disorders of the CNS caused such as spinal cord trauma, optic nerve injury, glaucoma, and multiple sclerosis.
Learn More...

Blocking reactive zinc stimulates optic nerve regeneration. Top row: cross-sections through the mouse retina show very little reactive zinc in normal animals (purple staining, left), but high levels after the optic nerve is injured (right). Second row: Blocking the accumulation of reactive zinc with compounds called chelators enables many RGCs to survive for months after the optic nerve is injured. Panels show healthy RGCs in the normal retina (green cells, left), two weeks after optic nerve injury without further treatment (center) or treatment with a chelator (right). Bottom two panels show histological sections through the optic nerve two weeks after the nerve is injured in the absence of further treatment (upper panel) or treatment with a zinc chelator (bottom panel).

Deriving microglia from hematopoietic 
progenitor and stem cells

Derrick Rossi, PhD, of the Program in Cellular and Molecular Medicine, and colleagues have developed a method to circumvent current limitations to growing microglia in culture. Using a proprietary expansion media and protocol, the group is able to isolate rare hematopoietic progenitors and stem cells from peripheral blood and effectively expand to sufficient numbers for differentiation into microglia-like cells.

The microglia-like cells can be used to study neuro-immunity in different disease states and as a platform for drug discovery.

Learn More...

Cell morphology on days 14 and 42 of differentiation protocol; Functional phagocytosis analysis of microglia-like cell derived from HSCs.

For more information on these and other Boston Children's opportunities, please email TIDO and search our technologies online.
Mustafa Sahin

Prescriptions for accelerating neuroscience translation:
Q&A with Dr. Mustafa Sahin

Mustafa Sahin, MD, PhD, a neurologist at Boston Children’s Hospital, directs the Translational Neuroscience Center, which he founded several years ago to accelerate neuroscience research to the clinic. He also directs the hospital’s
Translational Research Program. In this interview with Boston Children’s Technology and Innovation Development Office (TIDO), Sahin talks about his motivations as a clinician-scientist and how he works with industry partners to move discoveries forward.

Read the full interview here.


Research News from the F.M. Kirby Neurobiology Center


Newly Issued Patents
Available for Partnering

Methods and compositions for the treatment of proliferative vascular disorders
Joyce Bischoff | US 9,737,514 |

Methods and apparatuses for treating vessels
James Lock | US 9,849,006 |

Method of reducing blood glucose
Umut Ozcan | US 9,730,985 |

Gene Editing
Methods and Compositions for the Production of siRNAs
Judy Lieberman | US 9,840,703 |

Method of making a deletion in a target sequence in isolated primary cells using Cas9 and two guide RNAs
Derrick Rossi | US 9,822,370 |

MetAP-2 inhibitor polymersomes for therapeutic administration
Robert D'Amato | US 9,782,489 | US 9,789,199 |

Therapeutic target for the treatment of cancers and related therapies and methods
Mark Puder | US 9,763,905 |

Method of enhancing hematopoietic  stem/progenitor cell engraftment
Leonard Zon | US 9,737,567 |

Combined chemical modification of sphingosine-1-phosphate (S1P) and CXCR4 signalling pathways for hematopoietic stem cell (HSC) mobilization and engraftment
Leonard Zon | US 9,763,980 |

Calmodulin inhibitors for the treatment of ribosomal disorders and ribosomapathies
Leonard Zon | US 9,827,252 |

Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza hemagglutinin
Stephen Harrison | EPO 2739312 |

Selectively disrupted whole-cell vaccine
Richard Malley | US 9,827,299 |

Diagnostic markers of Kawasaki disease
Hanno Steen | US 9,869,673 |

Stem Cell

High-throughput image-based chemical screening in zebrafish blastomere cell culture
Leonard Zon | US 9,771,560 |

Detection of human somatic cell reprogramming
George Daley | US 9,846,164 |

Inhibition and enhancement of reprogramming by chromatin modifying enzymes
George Daley | US 9,670,463 |

Select Recent Neuroscience Publications 

Purkinje cells derived from TSC patients display hypoexcitability and synaptic deficits associated with reduced FMRP levels and reversed by rapamycin. Sundberg M, Tochitsky I, Buchholz DE, et al. Mol Psychiatry. 2018 Feb.

mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex. Kelly E, Schaeffer SM, Dhamne SC, et al. Neuropsychopharmacology. 2017 Dec.

Selective Inactivation of Fibroblast Growth Factor 22 (FGF22) in CA3 Pyramidal Neurons Impairs Local Synaptogenesis and Affective Behavior Without Affecting Dentate Neurogenesis. 
Terauchi A, Gavin E, Wilson J, Umemori H. Front Synaptic Neurosci. 2017 Dec.

Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias. D'Gama AM, Woodworth MB, Hossain AA, et al.Cell Rep. 2017 Dec.

PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum. 
Smith L, Singhal N, El Achkar CM, et al.  Epilepsia. 2018 Jan.

Novel Models and Tools
Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model. Jobst-Schwan T, Schmidt JM, Schneider R, et al. PLoS One. 2018 Jan.

Identifying Rodent Resting-State Brain Networks with Independent Component Analysis. Bajic D, Craig MM, Mongerson CRL, et al. Front Neurosci. 2017 Dec.

A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity. Cartoni R, Pekkurnaz G, Wang C, et al. PLoS One. 2017 Sep.

A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions. Liu Y, Wang X, Li W, et al. Neuron. 2017 Aug.