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Margot Mayer-Proschel, Ph.D.

Contact Information

Phone Numbers

Appointment: (585) 273-1449

Administrative: (585) 273-1440

Office: (585) 273-1449

Fax: (585) 273-1450

Research Labs

Faculty Appointments

Biography

Research

1. Identification of lineage restricted precursor cells for cell replacement
The concept of progressive lineage restriction is well accepted for hematopoeisis but has not been established in such detail in the developing CNS. We are pursuing how lineage restriction is regulated in various brain regions of the CNS and have discovered that embryonic glial precursor cells do not directly generate terminally differentiated cell types, but give rise to other, more restricted precursor cell types before terminal differentiation. The identification of these different cell pools is critical for identifying ideal transplantable cells for therapeutic cell replacement approaches.
The therapeutic translation of our knowledge of precursor cells and their derivatives is demonstrated in our collaborative efforts on designing optimal repair strategies for spinal cord injuries. With our colleagues Drs. Chris Proschel, Mark Noble and Stephen and Jeanette Davies at the University of Colorado we showed that the transplantation of a defined embryonic astrocyte population into a dorsal transection models of SCI results in extensive regeneration associated with complete functional recovery. We are now in the process of extending these finding by devising a rational approach to identify the optimal cell source and cell population for SCI repair and by characterizing the graft cells and the injury site in respect to cell death, inflammation and cell division.
2. CNS precursor cells and their derivatives in human disease paradigms
The insights we have gained from studying CNS glial precursor cells has led to the idea that precursor cell populations are targets for a large number of developmental abnormalities associated with myelination defects in humans. Defects in myelination are associated with insults as diverse as genetic defects, exposure to toxicant or to nutritional deficiencies. Based on our precursor cell work, we hypothesize that adequate myelination of large areas of the mammalian brain will only be possible if precursor cells arise in adequate numbers and continue to develop normally throughout development. Any disruption of the precursor cell pool might hence be associated with myelination defects later in development.
Gestational Iron deficiency.
Our hypothesis of precursor cells being a major target during development is especially relevant for the pathology seen as a result of gestational nutritional iron deficiency. This world's most prevalent nutritional deficiency is associated with impaired myelination and results in cognitive defects in affected children. We have shown that embryonic CNS tissue is not protected from iron deficiency during pregnancy, as commonly thought, and that early glial precursor cell populations are highly sensitive to changes in tissue iron concentrations. We have established rat and mouse models of gestation iron deficiency with and without anemia to determine the impact of gestational iron deficiency on brain development with a focus on (i) early embryonic telencephalic development and (ii) myelination of the auditory nerve postnatally.
Ataxia Telangiectasia (AT)
A genetic disorder associated with widespread neurological defects is the devastating disease Ataxia telangiectasia (AT), caused by mutations in the ATM gene. The pathology is characterized by crippling ataxia beginning in late infancy followed by progressive CNS degeneration of the cerebellum. While the majority of research has been focused on the neuronal cell population affected in the cerebellum, we began to determine the extent of glial dysfunction on the progression of AT. Our result indicate that astrocytic function is severely impaired in AT CNS tissue and we show that AT mutant astrocytes are unable to maintain neuronal integrity and survival. This new discovery opens the possibility for generating new therapeutic strategies that target the dysfunction astrocytes in order to halt or abolish neuronal degeneration.

Credentials

Education

1986
MS | Julius Maximilian University
Immunology

1990
PhD | Inst. Of Virology & Immunology, Univ of Wurzburg
Virology/Microbiology

Post-doctoral Training & Residency

1990 - 1995
Dept of Developmental Biology, Ludwig Institute for Cancer Research, London, UK (Mentor: Mark Noble)

Awards

2007
Graduate Student Society Faculty Award
Sponsor: University of Rochester

2006
Excellence in Research incentive program Award
Sponsor: University of Rochester

2004
Excellence in Research incentive program Award
Sponsor: University of Rochester

2004
Trainee Academic Mentoring Award
Sponsor: University of Rochester

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Patents

Patent Title: Transplantation of Glial Restricted Precursor - Derived Astrocytes For Promotion of Axon Growth
Patent #: ZL200680040380.5
Issue Date: Jun 12, 2013
Country: China, People's Republic of
Invented By: Jeannette Davies, Stephen Davies, Margot Mayer-Proschel, Mark D Noble, Christoph Proschel

Patent Title: Telencephalic Glial-Restricted Cell Populations and Related Compositions and Methods
Patent #: ZL200880012443.5
Issue Date: Sep 11, 2013
Country: China, People's Republic of
Invented By: Margot Mayer-Proschel, Frederick Strathmann

Publications

Journal Articles

2/20/2023
Rudy MJ, Salois G, Cubello J, Newell R, Mayer-Proschel M. "Gestational iron deficiency affects the ratio between interneuron subtypes in the postnatal cerebral cortex in mice." Development.. 2023 Feb 20; Epub 2023 Feb 20.

8/30/2022
Hogestyn JM, Salois G, Xie L, Apa C, Youngyunpipatkul J, Pröschel C, Mayer-Pröschel M. "Expression of the human herpesvirus 6A latency-associated transcript U94A impairs cytoskeletal functions in human neural cells." Molecular and cellular neurosciences.. 2022 Aug 30; :103770. Epub 2022 Aug 30.

2/23/2022
Warren R, Dylag AM, Behan M, Domm W, Yee M, Mayer-Proschel M, Martinez L, O'Reilly MA. "Ataxia telangiectasia mutated is required for efficient proximal airway epithelial cell regeneration following influenza A virus infection." American journal of physiology. Lung cellular and molecular physiology.. 2022 Feb 23; Epub 2022 Feb 23.

Books & Chapters

2001
Chapter Title: PreGlial restricted Precursors
Book Title: Stem cells and CNS development
Author List: Noble M., Mayer-Proschel M.
Published By: Rao M. Humana Press Inc 2001

1998
Book Title: Isolation and purification of oligodendrocytes
Author List: Mayer-Proschel M.
Edited By: Ron McKay
Published By: John Wiley and Sons 1998

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