Margot Mayer-Proschel, Ph.D.

Margot Mayer-Proschel, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 633
Rochester, NY 14642

Office: (585) 273-1449
Lab: (585) 273-2407
Administrative: (585) 273-1440
Fax: (585) 273-1450

Research Bio

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.

Patents

Use of Astrocytes Derived from Glial Restricted Precursor Cells (GDAs), Either by Themselves or in Combination with Other Compounds for Injury Repair for the Promotion of Linear Axon Regeneration in the Damaged Central Nervous System (CNS)

United States Serial NO.: 12/064,778
Filed Date: August 28, 2006
Title: Transplantation of Glial Restricted Precursor - Derived Astrocytes For Promotion of Axon Growth
Invented by: Chris Proschel, Margot Mayer-Proschel, Mark Noble, Jeannette Davies, Stephen Davies
Use of Astrocytes Derived from Glial Restricted Precursor Cells (GDAs), Either by Themselves or in Combination with Other Compounds for Injury Repair for the Promotion of Linear Axon Regeneration in the Damaged Central Nervous System (CNS)

United States Serial NO.: 200680040380.5
Filed Date: August 28, 2006
Title: Transplantation of Glial Restricted Precursor - Derived Astrocytes For Promotion of Axon Growth
Invented by: Chris Proschel, Margot Mayer-Proschel, Mark Noble, Jeannette Davies, Stephen Davies
Novel Glial Restricted Precursor Cells in the Embryonic Telencephalon (tGRPs)

United States Serial NO.: 12/596,223
Filed Date: April 16, 2008
Title: Telencephalic Glial-Restricted Cell Populations and Related Compositions and Methods
Invented by: Margot Mayer-Proschel, Frederick Strathmann
Novel Glial Restricted Precursor Cells in the Embryonic Telencephalon (tGRPs)

United States Serial NO.: 200880012443.5
Filed Date: April 16, 2008
Title: Telencephalic Glial-Restricted Cell Populations and Related Compostions and Methods
Invented by: Margot Mayer-Proschel, Frederick Strathmann

Recent Journal Articles

Showing the 5 most recent journal articles. 49 available »

2012 Apr 4
Lee DL, Strathmann FG, Gelein R, Walton J, Mayer-Pröschel M. "Iron deficiency disrupts axon maturation of the developing auditory nerve." The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2012 Apr 4; 32(14):5010-5.
2011 Apr 20
Tanner DC, Cherry JD, Mayer-Pröschel M. "Oligodendrocyte progenitors reversibly exit the cell cycle and give rise to astrocytes in response to interferon-?." The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2011 Apr 20; 31(16):6235-46.
2011
Mihaila C, Schramm J, Strathmann FG, Lee DL, Gelein RM, Luebke AE, Mayer-Pröschel M. "Identifying a window of vulnerability during fetal development in a maternal iron restriction model." PloS one. 2011 6(3):e17483. Epub 2011 Mar 15.
2008
Han R.; Yang Yin M.; Dietrich J.; Luebke A.; Mayer-Proschel M.; Noble, M. "Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the CNS". J Biol. 2008; 7(4). Link
2008
Davies JE; Proschel C; Zhang N; Noble M; Mayer-Proschel M; Davies SA. "Transplanted astrocytes derived from BMP or CNTF treated glial restricted precursors have opposite effects on recovery and allodynia after spinal cord injury". J Biol.. 2008; 7(24). Link

Current Appointments

Associate Professor - Department of Biomedical Genetics (SMD) - Primary
Associate Professor - Department of Neurobiology and Anatomy (SMD)

Education

PhD | Virology/Microbiology | Inst. Of Virology & Immunology, Univ of Wurzburg1990
MS | Immunology | Julius Maximilian University1986

Post-Doctoral Training & Residency

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