Medical College of Wisconsin
Medical College of Wisconsin Medical College of Wisconsin
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Ophthalmology and Visual Sciences

Scalabrino Laboratory

Gene therapy is radically changing medicine, particularly to treat inherited neurodegenerations like vision loss. However, while some therapies initially improve function, cell loss continues. The reason for this is currently unknown, though it likely results from a combination of global issues (vector, dose, delivery) and disease biology (pathology at intervention time, expression levels). The main goal of the Scalabrino Lab is to halt inherited retinal disorders by studying retinal circuitry and engineering new molecular therapies that better address the dysfunction.
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Research Areas

The Scalabrino Lab utilizes a comprehensive approach to understand the neurobiology of vision loss and therapy: multielectrode array recordings of retinal ganglion cells to functionally define disease and rescue, transcriptomics to determine molecular signatures of neurodegeneration, natural behavior to link ex vivo function to in vivo visual performance, and molecular engineering to create designer biologics such as adeno-associated viral vectors.

What causes continued photoreceptor degeneration following gene therapy?

In previous studies on a mouse model of retinitis pigmentosa, we found genetically rescued retinas continued to degenerate, as has been reported in additional animal models and patients of many neurodegenerations. A major goal of the Scalabrino lab will be to understand what factors contribute. By discovering the cause for continued cell loss, we can develop therapies that target the deficit, such as gene augmentation or cell replacement strategies.

How do mutation-specific and species-specific differences impact retinal pathogenesis?

Photoreceptor degenerations can be caused by >200 different gene mutations, making gene replacement strategies costly in both time and resources. This makes a gene-agnostic approach attractive, as it would reach more patients than gene replacement and reduce R&D-associated healthcare costs to make it accessible to a diverse population. There is currently a major bottleneck to developing a gene-agnostic therapy: much retinal disease research is performed on a few rodent models. While there are advantages to studying these lines, their relevance to human disease is limited. Thus, a second goal of the lab is to create and investigate diverse models of disease to look for common features a therapy may be able to solve irrespective of mutation, as well as discover mutation specific points of failure.

What developmental mechanisms can be leveraged to rescue retinal disease?

In both neural disease and development, cells undergo a variety of changes related to neuroplasticity, such as synaptogenesis and pruning, autophagy, and temporal gene expression. A third goal of the lab is to harness genes involved in neural development to improve gene and cell therapies for a wide variety of retinal diseases including retinitis pigmentosa, lebers congenital amaurosis, congenital stationary night blindness, and cone-rod dystrophy.

Image from a visually guided prey capture test

Scalabrino Lab cricket hunting


Retina expressing a calcium sensor in select retinal ganglion cells

Scalabrino Lab PV_GCaMP




Confocal microscope image of retinal ganglion cells expressing an engineered receptor (red) with the ligand (green) used to chemically manipulate cellScalabrino Lab PV_HaloTag

Multielectrode array used to record from ex vivo retinas

Scalabrino Lab Multielectrode array

 

Current Members

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Miranda L. Scalabrino, PhD

Assistant Professor of Ophthalmology & Visual Sciences; Assistant Professor of Cell Biology, Neurobiology and Anatomy

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Molly Rose Rasper

Research Technologist II

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Katharine Schwister

Graduate Student

Research Opportunities

Graduate student opportunities

If you are a PhD or Master's student at MCW or you are considering applying to MCW in a neuroscience, physiology, or cell biology related field, and you are interested in the visual system, treating blinding diseases, or learning how to apply novel computational approaches to complex neurobiological data, please contact us.

Undergraduate opportunities

Are you an undergraduate in the Milwaukee area and want to get research experience in a laboratory doing biomedical research related to vision and neuroscience? We have a variety of projects you could contribute to. Please contact us for more information. Please include a brief description of what science, engineering and/or math classes you have taken, your planned major, and a few sentences about what you hope to pursue after college.

We also have opportunities for summer students.

Research Technician opportunities

If you have a bachelor’s degree in any area of the natural sciences, math, engineering or computer science, and you want to bolster your research experience in an inclusive and dynamic environment, please contact us for information about research technician positions.

Support the Scalabrino Lab

The Scalabrino Lab could not exist without the generosity and support of many foundations, federal agencies and individual donors. Funds donated to the program are used to acquire new equipment and research consumables, to help train students and fellows, to enable the presentation of our research findings at scientific meetings and to fund positions for support staff.

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Recent Publications

Publications of Miranda L. Scalabrino PhD from the Faculty Collaboration Database

Contact

Scalabrino Lab

(414) 955-7803

mscalabrino@mcw.edu