43563-Monje, Paula
Faculty

Paula Monje, PhD

Associate Research Professor of Neurological Surgery

Address
Indiana University Health Neuroscience Research Bldg.
320 W. 15th Street, Suite 514G

Indianapolis, IN 46202

Bio

Basic biology and therapeutic applications of Schwann cell cultures

My line of research focuses on the study of Schwann cells, the glial cells in peripheral nerves that take the important role to form a myelin sheath around axons. The myelin is a specialized membrane structure that effectively insulates axons and enables the rapid conduction of electrical impulses. Schwann cells also promote axon regeneration after injury and this extraordinary capability has converted them into excellent candidates in cell therapy approaches targeting injuries in the spinal cord and peripheral nerve. My lab uses cultured Schwann cells as platforms for basic cell signaling studies, in vitro models of injury and myelination, and drug testing. We also use them in experimental cell therapy to understand mechanisms of nerve tissue repair in the central nervous system. We place special focus on the development of new methods to improve the potency of the cells both in culture and after transplantation using Schwann cells obtained from humans and various species of experimental animals.

Signaling mechanisms underlaying Schwann cell proliferation and differentiation
Efforts in my lab are geared to understand the molecular control of Schwann cell proliferation and differentiation into myelin-forming cells. For this, we use traditional signal transduction approaches in combination with state-of-the-art technologies, such as whole transcriptome sequencing via RNA-seq, to enable a broader description of signaling networks underlying cell function. In particular, we are interested in understanding how signaling from the ubiquitous second messenger cAMP controls the onset, maintenance and reversal of the state of differentiation in Schwann cells and how this connects to cell cycle control.

Development of culture systems for primary Schwann cells
The culturing of Schwann cells requires sophisticated methods for the growth of the cells in vitro. This is most important when setting up the conditions necessary to allow the complex process of myelination to take place in the simplified environment of the culture dish. My laboratory works on developing and optimizing cell culture methods for primary Schwann cells and designing adaptations for cells derived from different species, including humans, and stages of nerve development. We have established novel protocols for the isolation, purification, amplification and characterization of Schwann cells from human nerves. We are currently working on developing cell type-specific, cell-based assays to reliably identify human Schwann cells in culture and determine their function for uses in cell therapy and in vitro modeling in Charcot-Marie-Tooth disease, a genetic condition that affects Schwann cells in peripheral nerves.

Schwann cell transplantation in the spinal cord

In collaboration with Dr. Xiao-Ming Xu, we are exploring the use of Schwann cell transplants to foster nerve regeneration and recovery of function after spinal cord injury. We have particular interest in developing clinically relevant strategies that can increase the survival, proliferation and myelination of human Schwann cells grafted in the spinal cord. For this, we apply assorted genetic and pharmacological treatments to the cells themselves and the animals both prior to and after implantation.  

Key Publications

Signaling pathways controlling Schwann cell proliferation and differentiation

Monje PV, Bunge MB, Wood PM (2006) Cyclic AMP synergistically enhances neuregulin-dependent ERK and Akt activation and cell cycle progression in Schwann cells. Glia 53(6):649-659.

Monje PV, Athauda G, Wood PM (2008) PKA-mediated gating of neuregulin-dependent ERBB2-ERBB3 activation underlies the synergistic action of cAMP on Schwann cell proliferation. J. Biol. Chem. 283(49):34087-100.

Monje PV, Rendon S, Athauda G, Bates M, Wood PM, Bunge MB (2009) Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. Glia 57:947-961.

Monje PV, Soto J, Bacallao K, Wood PM (2010) Schwann cell dedifferentiation is independent of mitogenic signaling and uncoupled to proliferation: role of cAMP and JNK in the maintenance of the differentiated state. J. Biol. Chem. 285:31024-36.

Bacallao K, Monje PV (2013) Opposing roles of PKA and EPAC in the cAMP-dependent regulation of Schwann cell proliferation and differentiation. PLoS One 8 (12): e82354.

Bacallao K, Monje PV (2015) Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination. PLoS One 10 (2): e0116948.

Monje PV (2015) To myelinate or not to myelinate: Fine tuning cAMP signaling in Schwann cells to balance cell proliferation and differentiation. Neural Regeneration Research 10 (12): 1936-1937. PMID: 26889176.

Camarena V, Sant DW, Huff TC, Mustafi S, Muir RK, Aron AT, Chang CJ, Renslo AR, Monje PV, Wang G. (2017) Cyclic adenosine monophosphate to play a novel role in regulating DNA demethylation and gene transcription by augmenting the intracellular reactive Fe(II) pool. eLIFE, 1-21.

Piñero G, Berg R, Andersen N, Setton-Avruj P, Monje P.V. (2017) Lithium reversibly inhibits Schwann cell proliferation and differentiation without inducing myelin loss. Mol. Neurobiol. 54 (10): 8287-8307.  

Soto, J, Monje, P.V. (2017) Axon-contact driven Schwann cell dedifferentiation. Glia 65 (6), 864-882.

 

Development of new methods and assays to study Schwann cells

Andersen N, Srinivas S, Piñero G, Monje P.V. (2016) A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves. Scientific Reports 6, 31781.

Monje P.V. (2018) Scalable neuron-free assays for the differentiation and dedifferentiation of cultured Schwann cells. Methods Mol. Biol. 1739: 213-232.

Andersen N.D., Monje P.V. (2018) Isolation, culture and cryopreservation of adult rodent Schwann cells derived from immediately dissociated teased fibers. Meth. Mol. Biol. 1739: 49-66.

Ravelo K.M., Andersen N.D., Monje P.V. (2018) Magnetic-activated cell sorting for the fast and efficient separation of human and rodent Schwann cells from mixed cell populations. Meth. Mol. Biol. 1739: 87-109.

Monje P.V, Sant D, Wang G. (2018) Phenotypic and functional characteristics of human Schwann cells as revealed by cell-based assays and RNA-seq. Mol. Neurobiol. 55 (8):6637-6660.

Uses of Schwann cells in cell therapy

Bunge M.B., Monje P.V., Khan A. and Wood P.M. (2017). From transplanting Schwann cells in experimental rat spinal cord injury to their transplantation into human injured spinal cord in clinical trials. Prog Brain Res.  231:107-133. PMID: 28554394

Link to publications list

http://www.ncbi.nlm.nih.gov/sites/myncbi/paula.monje.1/bibliography/45534113/public/?sort=date&direction=ascending.

For a reference to Schwann cell methods

Monje P.V., Kim H.A. (Eds). (2018) Schwann cells: methods and protocols. 1st Ed. In: Methods Mol. Biol. 1739, XIII - 488 (31 chapters). ISBN: 978-1-4939-7648-5 (hardcover), 978-1-4939-7649-2 (eBook).

 

https://www.springer.com/us/book/9781493976485

For a reference to Schwann cell products

https://www.kerafast.com/section/676/paula-v-monje-phd

Titles & Appointments

  • Associate Research Professor of Neurological Surgery
  • Education
    2001 PhD National University of the South
    1994 BS National University of the South

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