My research focuses on the study of peripheral nerve Schwann cells (SCs) and their dual role in forming myelin and promoting axon regeneration after injury and transplantation. My lab carries out signal transduction studies on molecular mechanisms underlying the proliferation, survival, differentiation (i.e, myelination) and dedifferentiation (i.e., reprogramming) of SCs using sophisticated in vitro systems combined with molecular, pharmacological, and ‘omics’ approaches. My expertise in cell signaling is broad. I have studied normal and oncogenic signaling mediated by membrane and nuclear receptors, second messengers, kinase cascades, and transcription factors via native and reconstituted gene expression systems, analysis of protein-protein interactions, post-translational modifications (phosphorylation), epigenetic marks (DNA/histone modifications), and gene regulatory networks (transcriptome profiling via RNA-seq). To perform mechanistic studies, I developed simplified bioassays consisting of neuron-free and reconstituted SC-neuron systems to quantitatively evaluate myelin gene expression, myelin formation & degradation, and cell-cell interactions (or signaling) via membrane contact and soluble factors. In addition, I have devised assorted methods for the isolation, purification and analysis of mature and developing SCs from humans and animal models. Approaches under investigation include development of 3D SC/neuron systems, cell products and bioassays for transplantation and in vitro modeling in peripheral neuropathies cancer. Our innovations in culture technologies have led to various initiatives in ad hoc cell manufacturing, commercialization of cell products, and consultancy with scientists in academia and the biopharma. At my former institution, The Miami Project to Cure Paralysis, I contributed to the development of autologous human SCs for FDA-regulated cell transplantation trials. Over the years, I have established invaluable material resources (such as cryobank of neurons and glial cells, tissues and cell lines from the PNS and CNS), but most importantly, an expanding network of colleagues and collaborators worldwide that greatly enrich the scope of my work.
https://scholars.uky.edu/en/persons/paula-monjePeer-reviewed Research Articles
(*) Indicates corresponding author
1. Monje P.V., Baran E.J. (1996) On the formation of weddellite in Chamecereus silvestrii, a cactaceae species from Northern Argentina. Z. Naturforschung C-A 51c: 426-428.
2. Monje P.V., Baran E.J. (1997) On the formation of whewellite in the cactaceae species Opuntia mycrodasys. Z. Naturforschung C-A 52 c: 267-269.
3. Monje P., Boland R. (1999) Characterization of membrane estrogen binding proteins from rabbit uterus. Mol. Cell. Endocrinol. 147: 75-84. PMID: 10195694
4. Monje P.V., Baran E.J. (1999) First evidences of the bioaccumulation of -quartz in cactaceae. J. Plant Physiol. 157 (4): 457-460.
5. Monje P., Boland R. (2001) Subcellular distribution of native estrogen receptor and isoforms in rabbit uterus and ovary. J. Cell. Biochem. 82: 467-479. PMID: 11500923
6. Monje P., Zanello S., Holick M., Boland R. (2001) Differential cellular localization of estrogen receptor in uterine and mammary cells. Mol. Cell. Endocrinol. 181: 117-129. PMID: 11476946
7. Milanesi L., Monje P., Boland R. (2001) Presence of estrogens and estrogen receptor-like proteins in Solanum glaucophyllum. Biochem. Biophys. Res. Comm. 289: 1175-1179. PMID: 11741316
8. Monje P., Boland R. (2002) Expression and cellular localization of naturally occurring estrogen receptors in uterine and mammary cell lines. J. Cell. Biochem. 86:136-144. PMID: 12112024
9. Monje P.V., Baran E.J. (2002) Characterization of calcium oxalates generated as biominerals in cacti. Plant Physiol. 128: 707-713. PMID: 11842173
10. Monje P., Marinissen M.J., Gutkind J.S. (2003) The phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor. Mol. Cell. Biol. 23: 7030-7043. PMID: 12972619
11. Monje P.V., Baran E.J. (2004) Complex biomineralization pattern in Cactaceae. J. Plant Physiol. 161:121-123. PMID: 15002673
12. Monje P., Hernandez-Losa J., Lyons R., Castellone M., Gutkind J.S. (2005) Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl-isomerase Pin1. J. Biol. Chem. 280 (42): 35081-35084. PMID: 16123044
13. Monje P.V, Baran E.J. (2005) Evidence of formation of glushinskite as a biomineral in a Cactaceae species. Phytochemistry 66 (5): 611-614. PMID: 15721954
14. Monje P.V., Bunge M.B., Wood P.M. (2006) Cyclic AMP synergistically enhances neuregulin-dependent ERK and Akt activation and cell cycle progression in Schwann cells. Glia 53 (6):649-659. PMID: 16470843
15. Monje P.V.*, Athauda G., Wood P.M. (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. PMID: 18799465
16. Maldonado E.N., Alderson N.L., Monje P.V., Wood P.M., Hama H. (2008) FA2H is responsible for the formation of 2-hydroxy galactolipids in peripheral nervous system myelin. J. Lipid Res. 49: 153-161. PMID: 17901466
17. Gess B., Halfter H., Kleffner I., Monje P.V., Athauda G., Wood P., Young P., Wanner I. (2008) Inhibition of N-cadherin and -catenin function reduces axon-induced Schwann cell proliferation. J. Neurosc. Res. 86: 797-812. PMID: 17941050
18. Monje P.V.*, Rendon S., Athauda G., Bates M., Wood P.M., Bunge M.B. (2009) Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. Glia 57: 947-961. PMID: 19053056
19. Monje P.V., Baran E.J. (2009) Characterization of calcium oxalate biominerals in Pereskia species (Cactaceae). Z. Naturforschung. 64c: 763-766. PMID: 20158142
20. Monje P.V.*, Soto J., Bacallao K., Wood P.M. (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. PMID: 20634285
21. Monje P.V., Baran EJ. (2010) Characterization of calcium oxalate biominerals in some succulent (non-Cactaceae) plant species. Z. Naturforschung C 65 (7-8): 429-432. PMID: 20737908
22. Bacallao K., Monje P.V.* (2013) Opposing roles of PKA and EPAC in the cAMP-dependent regulation of Schwann cell proliferation and differentiation. PLoS One 8 (12): e82354. PMID: 24349260
23. Bacallao K., Monje P.V.* (2015) Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination. PLoS One 10 (2): e0116948. PMID: 25705874
24. Monje P.V.* (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): 1936-7. PMID: 26889176
25. 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. PMID: 27549422
26. 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. Molecular Neurobiology 54 (10): 8287-8307. PMID: 27917448
27. Soto J., Monje P.V.* (2017) Axon-contact driven Schwann cell dedifferentiation. Glia 65 (6), 864-882. PMID: 28233923
28. Camarena V., Sant D.W., Huff T.C., Mustafi S., Muir R.K., Aron A.T, Chang C.J., Renslo A.R., Monje P.V., 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 Dec 14;6: e29750. PMID: 29239726
29. Perez E., Bracho O., Ein L., Szczupak M., Monje P.V., Fernandez-Valle C., Abdulaziz A., Ivan M., Morcos J., Hoffer M., Eshraghi A., Angeli S., Telischi F., Dinh C.T. (2018) Fluorescent detection of merlin-deficient Schwann cells and primary human vestibular schwannoma cells using sodium fluorescein. Otology & Neurotology 39(8):1053-1059. PMID: 30001282
30. Piñero G., Usach V., Soto P., Monje P.V., Setton-Avruj P. (2018) EGFP transgene: a useful tool to track transplanted bone marrow mononuclear cell contribution to peripheral remyelination. Transgenic Research 27: 135-153. PMID: 29453733
31. Bademci G., Abad C., Incesulu A., Rad A. Alper O., Kolb S.M., Cengiz F.B., Diaz-Horta O., Silan F., Mihci E., Ocak E., Najafi M., Maroofian R., Yilmaz E., Nur B.G., Duman D., Guo S., Sant D.W., Wang G., Monje P.V., Haaf T., Blanton S.H., Vona B., Walz K., Tekin M. (2018) MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss. Human Genetics 137 (6-7): 479-486. PMID: 29982980
32. 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. Molecular Neurobiology 55 (8):6637-6660. PMID: 29327207
33. Ein L., Bracho O., Monje P., Fernandez-Valle C., Bas E., Thomas G., Weed D., Sargi Z., Dinh C. (2019) Inhibition of Tropomyosine Receptor Kinase B on the Migration of Human Schwann Cell and Dispersion of Oral Tongue Squamous Cell Carcinoma In Vitro. Head & Neck 41(12):4069-4075. PMID: 31497919
34. Ein L., Mei C., Bracho O., Bas E., Monje P., Weed D., Sargi Z., Thomas G., Dinh C. (2019) Modulation of BDNF-TrkB Interactions on Schwann Cell-Induced Oral Squamous Cell Carcinoma Dispersion In Vitro. Anticancer Research 39 (11): 5933-5942. PMID: 31704818
35. Huff TC, Camarena V., Sant DW., Wilkers Z., Van Booven D, Aron AT, Muir RK., Renslo AR., Chang CJ., Monje P.V., Wang G. (2020) Oscillatory cAMP Signaling Rapidly Alters H3K4 Methylation and Gene Expression. Life Science Alliance Jan, 3 (1). doi: 10.26508/lsa.201900529. PMID: 31882444.
36. Monje P.V.* (2020) The properties of human Schwann cells: lessons from in vitro culture and transplantation studies. Glia 68 (4): 797-810. PMID: 32027424
37. Huff T., Sant D.W., Camarena V., Van Booven D., Andrade N., Mustafi S., Monje P.V.*, Wang G*. (2020) Vitamin C promotes DNA demethylation of genes regulating Schwann cell development and function. J. Neurochemistry doi: 10.1111/jnc.15015. [Online ahead of print]. PMID: 32219848
38. Monje P.V.* (2020) Schwann cell cultures: biology, technology and therapeutics. Cells. 9, 1848 (1-24 p). Special Issue on ‘Schwann cells: from formation to clinical significance’. PMID: 32781699
39. Peng K., Sant D., Andersen N., Silvera S., Camarena V., Graham R., Khan A., Xu, X.M., Wang G., Monje P.V.* (2020) Magnetic separation of cultured peripheral nerve resident cells underscores key molecular features of human Schwann cells and fibroblasts: an immunochemical and transcriptomics approach. Scientific Reports 10(1):18433. PMID: 33116158
40. Cohen E, Pena S., Mei C., Bracho O., Marples B. Elsayyad N., Goncalves S., Ivan M., Monje P.V., Liu X-Z., Fernandez-Valle C., Telischi F., Dinh C.T.* (2021) Merlin-Deficient Schwann cells are more Susceptible to Radiation Injury than Normal Schwann Cells in Vitro. J Neurol Surg B. DOI: 10.1055/s-0040-1722283
41. Monje P.V.*, Deng L, Xu, X.M. (2021) Human Schwann cell transplantation in spinal cord injury: prospects and challenges for translational medicine. Frontiers in Cellular Neuroscience https://doi.org/10.3389/fncel.2021.690894
42. Monje P.V.*, Bacallao K., Aparicio G., Lalwani A (2021) Heregulin activity assays for residual testing of cell therapy products. Biological Procedures Online 23, 22, https://doi.org/10.1186/s12575-021-00157-5
43. Chau M.J., Quintero J.E., Monje P.V., Voss R., Gerhardt G., van Horne C. (2022) Using an injury paradigm to enhance the regenerative mechanisms of an investigational human cell therapy. Cell Transplantation. doi: 10.1177/09636897221123515. PMID: 36169034; PMCID: PMC9523845.
44. Aparicio G.I., León A., Gutiérrez Fuster R., Monje P.V.*, and Scorticati C. * (2023) Endogenous glycoprotein M6a is involved in neurite outgrowth in rat dorsal root ganglion neurons. Biomolecules 13(4), 594. https://doi.org/10.3390/biom13040594
45. Dinh C.T., Chen S., Nourbakhsh A., Padgett K., Johnson P., Goncalves S., Bracho O., Bas E., Bohorquez J., Monje P.V., Fernandez-Valle C., Elsayyad N., Liu X.-Z., Welford S., Telischi F. (2023) Single Fraction and Hypofractionated Radiation Causes Cochlear Damage, Hearing Loss, and Reduced Viability of Merlin-Deficient Schwann Cells. Cancers Volume 15, Issue 10, Article number 2818 (Open access), DOI 10.3390/cancers15102818
46. Aparicio G.I., Monje P.V.* (2023) Human Schwann Cells in vitro I. Nerve Tissue Processing, Pre-degeneration, Isolation and Culturing of Primary Cells. Bio-protocol 13(15): e4748. DOI: 10.21769/BioProtoc.4748.
47. Monje, P.V.* (2023) Human Schwann cells in vitro II. Passaging, purification, banking and labeling of established cultures. Bio-protocol 13(22): e4882. DOI: 10.21769/BioProtoc.4882.
48. Monje, P.V.* (2023). Human Schwann Cells in vitro III. Analytical Methods and a Practical Approach for Quality Control. Bio-protocol 13(19): e4840. DOI: 10.21769/BioProtoc.4840.
49. Aparicio G.I., Quintero JE., Plum L., Deng, L.X., Wanczyk K., Murphy M., Gerhardt G., Van Horne C, Monje P.V.*. Immunological profiling of cellular and noncellular components from human peripheral nerve (in preparation)
Books and Chapters
(*) Indicates corresponding or leading editor
1. Boland R., de Boland A.R., Vazquez G., Santillán G., Monje P. (1997) Molecular aspects of rapid responses to 1,25 (OH)2-vitamin D3. In: Vitamin D: Chemistry, Biology and Clinical Applications of the Steroid Hormone. AW Norman et al. (Eds.), Walter and Gruyter Co., NY. pp 361-368.
2. Capiati D., Santillán G., Rossi A., Monje P., Boland, R. (2003) Nuclear vitamin D (VDR) and estrogen receptors in the membrane of muscle and breast cancer cells. In: The Identities of Membrane Steroid Receptors: and Other Proteins Mediating Nongenomic Steroid Action. Cheryl S. Watson (Ed.). Kluwer Academic Publishers. pp 57-66.
3. Monje P.V., Baran E.J. (2004) Plant Biomineralization. In: Advances in Plant Physiology. A. Hemantaranjan (Ed.), Scientific Publishers, Jodhpur, India. Vol. 7: pp 403-419.
4. Baran E.J., Monje P.V. (2008) Oxalate Biominerals. In: Metal Ions in Life Sciences. Biomineralization: from Nature to Application. A. Siegel, H. Siegel and R. Siegel Eds. Vol 4, pp 219-254.
5. 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. Progress in Brain Research, 231: 107-133. Dunnett S.B., Björklund A (eds). Academic Press Amsterdam. PMID: 28554394
6. Piñero G., Setton-Avruj P., Monje P.V.* (2017) Lithium in biological systems: an ubiquitous regulator of cell function. In: Lithium: a natural strategic resource. E.J. Baran (Ed.). National Academy of Sciences from Argentina, Buenos Aires, Argentina, ISBN 978-987-4111-19-7, pp 112-126. (in Spanish).
7. 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. PMID: 29546700
8. 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. PMID: 29546702
9. Monje P.V.* (2018) Scalable neuron-free assays for the differentiation and dedifferentiation of cultured Schwann cells. Meth. Mol. Biol. 1739: 213-232. PMID: 29546710
10. Monje P.V.*, Kim H.A. (2018) Preface. Schwann cells: methods and protocols. (2018) Methods Mol. Biol. 1739. Pages: V-VI
11. 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). ISSN: 1064-3745. eISSN: 1940-6029