NAME: Emma Elizabeth Frost
Address: Dept. Radiology, NM Research Division, Johns Hopkins University, 720 Rutland Avenue, Traylor 217, Baltimore MD, USA, 21205
Email address
EDUCATION
1999 Ph.D. Anglia Polytechnic University, Cambridge, UK in association with WellcomeTrust Cancer Research Campaign Institute for Cancer Research and Developmental Biology, University of Cambridge, UK
1994 B.Sc. Combined Honors in Cell and Molecular Biology and Biomedical Sciences (1st class)
Anglia Polytechnic, Cambridge, UK
Invited Lecturer in the Graduate Developmental Neuroscience Program, University of Maryland Baltimore, Medical School, 2004.
Invited Lecturer in the Graduate Developmental Neuroscience Program, Uniformed Services University for the Health Sciences, 2002.
Assistant demonstrator for 1st and 2nd year undergraduate students in Medical and Natural Sciences at University of Cambridge, UK.
Personal tutor to British pre-college students in Biological Sciences.
EMPLOYMENT HISTORY
October 2002 - Date: Research Associate (entry level faculty), Dept. Radiology, NM Research Division, Johns Hopkins University, Baltimore, MD.
I am currently working in the lab of Dr. Jeff Bulte studying the migration of transplanted stem cells in various disease models. We use a superparamagnetic nanoparticle to label the cells so that they are visible on MR Images, allowing us to track the movement of the cells within an individual animal over time. The intital studies in this project are dedicated to validating the method, and involves using MR Imaging to track the cells, and then co-localizing the presence of the labeled cells with the hypointense signals seen on MR using histology. We are using several different animal models of human disease including motorneuropathy, Parkinson's, stroke, glomerular nephritis and cancer. In addition I am using transplanted stem cells to evaluate the role of the environment in the regulation of migration of cells during cortical development, furthering my interests in the mechanisms regulating the migration of glial cells in the developing brain.
November 1998 – October 2002: Postdoctoral Research Fellow, Department of Anatomy and Cell Biology, Uniformed Services University for the Health Sciences, Bethesda, MD.
I investigated the effect of growth factors on the proliferation and migration of adult spinal cord (ASC) oligodendrocyte precursors in vitro. The in house mouse model of remyelination required intracranial injection of MHV into adult mice and the analysis of the extent of demyelination by behavioural testing over the subsequent 4-week period. Glial cells were isolated from the spinal cords of those mice exhibiting severe demyelination, and cultured to study the cells’ response to different growth factors. I used BrdU incorporation as an index of proliferation, and immunohistochemistry to identify specific the cells’ stage in the lineage, for analysis. I also used a modification of the Varani agarose drop assay to assay the migration of ASC oligodendrocytes, and to characterise antagonists for the different growth factors used in the experiments above. An extension of this project included in situ hybridisation studies to investigate changes in growth factor expression patterns in the remyelinating spinal cord. In parallel I used the Varani drop assay and BrdU incorporation to investigate signaling pathways in the regulation of neonatal oligodendrocyte precursor cell behavior by growth factors.
1995 – 1998: Research Assistant, WellcomeTrust Cancer Research Campaign Institute for Cancer Research and Developmental Biology, University of Cambridge.
Ph.D. Title “The role of extracellular cues in the regulation of oligodendrocyte behavior in vitro.”
For my Ph.D. thesis I studied the interactions of ECM proteins and axons, with oligodendrocytes in vitro (8 & 10). In parallel to this I investigated the role of oligodendrocyte integrins in these interactions (9 & 12), and the effect of Gro-? on oligodendrocyte migration in vitro (13). This involved: culturing mixed glial cell cultures from neonatal rat and mouse brain, the preparation of pure populations of rat and mouse oligodendrocyte and embryonic mouse and rat dorsal root ganglion neurones for use in a xeno-culture system; and development of that system. Analysis of cell migration using a microchemotaxis chamber; immunofluorescent staining of cells; use of a confocal microscope, and computerised image analysis. I also looked at gene splicing during differentiation of glial cells, using semi-quantitative radioactive RT-PCR to identify specific genes of interest. I was co-editor of the weekly Institute Newsletter.
1989 - 1995: R7 grade Research Technician, Department of Pharmacology, University of Cambridge
'87 - ‘89: R6 grade Technician, Department of Pharmacology, University of Cambridge, UK.
'85 - '87: Trainee Research Technician, Department of Pharmacology, University of Cambridge, UK.
'82 - '85: Laboratory Technician, Strangeways Research Laboratory, Cambridge, UK.
PUBLICATIONS (Click on the green ball to go to the PubMed Link for this article)
Published abstracts of papers presented at meetings:
1990 - Fan, T.-P.D. & Frost, E.E. “A new in vitro assay for the study of endothelial cell wound repair.” Eur. J. Pharmacol. 183 (5): 1809. (presented at XIth International Congress of Pharmacology, Amsterdam, The Netherlands, 1-6 July 1990)
1995 - Michel, A.D., Chau, N.-M., Fan, T.-P.D., Frost, E.E. & Humphrey, P.P.A.
“Differences between the high affinity [3H]aßmeATP binding sites in rat vas deferens and in a rat aortic endothelial-derived cell line.” Br. J Pharmacol. 115, 767-774
Conference papers:
1. 1992 – Fan, T.-P.D., Frost, E.E. & Wren, A.D. “A multichannel wounding device for the study of vascular repair in vitro.” In Steiner, R., Weisz, P.B. and Langer, R. (Eds.) Angiogenesis. Key Principles-Science-Technology-Medicine. Pp.315-320 (Basel: Birkhauser Verlag AG).
2. 1997 - Buttery, P., Frost, E., Milner, R., & ffrench-Constant, C. “Integrin expression and function in oligodendroglia.” J. Neurochem. 69, S230
3. 1999 - Armstrong, R.C., Simpson, P.B., Frost, E.E. and Nielsen, J.A. “Extracellular signals and intracellular mechanisms involved in oligodendrocyte progenitor migration” J. Neurochem. 72, S49D
4. 2000 - Frost, E.E., Nielsen, J.A. and Armstrong, R.C. “Platelet derived growth factor and fibroblast growth factor 2 regulate oligodendrocyte progenitor proliferation in cultures of remyelinating adult mouse spinal cord.” J Neurochem. 74, S58B
5. 2000 - Messersmith, D.J., Murtie, J.C., Le, T.Q., Frost, E.E. and Armstrong, R.C. “Fibroblast growth factor 2 (FGF2) and FGF receptor (FGFR) type expression in remyelinating lesions.” J. Neurochem. 74, S58A
Invited Paper:
6. 2000 - Frost E.E., Milner R, and ffrench-Constant, C
“Migration assays for oligodendrocyte precursor cells.” In “Extracellular Matrix Protocols”. Ed. CH Streuli and ME Grant. Humana Press, Inc., Totowa, New Jersey, USA. Methods Mol Biol. 139, 265-78
139
Full refereed papers:
7. 1995 - Michel, A.D., Chau, N.-M., Fan, T.-P.D., Frost, E.E. and Humphrey, P.P.A.
“Evidence that [3H]aßmeATP labels a 5'-nucleotidase in an endothelial cell line.”. Br. J. Pharmacol. 115, 767-774
8. 1996 - Frost, E.E., Kiernan, B.W., Faissner, A. and ffrench-Constant, C.K.
“Regulation of oligodendrocyte precursor migration by extra-cellular matrix: evidence for substrate-specific inhibition of migration by Tenascin-C.” Developmental Neuroscience 18, 266-273
9 1997 - Milner, R., Frost, E.E., Nishimura, S., Edwards, G., Streuli, C., Pytela, R. and ffrench-Constant, C.
“Expression of avß3 and avß8 integrins during oligodendrocyte precursor differentiation in the presence and absence of axons.” Glia 21, 350-360
10. 1998 - Lauder, H., Frost, E.E., Hiley, C.R., and Fan, T.-P.D.
“Quantification of the repair process involved in the repair of a cell monolayer using an in vitro model of mechanical injury.” Angiogenesis 2, 67-80
11. 1999 - Kiernan, B.W., Garcion, E., Ferguson, J., Frost, E.E., Torres, E.M., Dunnett, S.B., Saga, Y., Aizawa, S., Faissner, A., Kaur, R., Franklin, R.J., and ffrench-Constant, C.
“Myelination and behavior of tenascin-C null transgenic mice.” Eur J Neurosci, 11(9), 3082-3092
12. 1999 - Frost, E.E., Buttery, P.C., Milner R., and ffrench-Constant, C.
“Integrins mediate an axonal survival signal for oligodendrocytes.” Curr Biol. 9(21), 1251-1254.
13. 2000 - Blaschuk, K.L., Frost, E.E. and ffrench-Constant, C.
“Over expression of the alphavbeta3 integrins leads to prolonged proliferation and delayed differentiation by oligodendrocyte precursor cells in vitro.” Development 127(9), 1961-1969.
14. 2000 - Messersmith, D.J., Murtie, J.C., Le, T.Q., Frost, E.E. and Armstrong, R.C.
“Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination.” J. Neuroscience Research 62:241-256
15. 2002 - Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, and Miller RH.
“The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration.” Cell. Aug 9;110(3):373-83
16.2002 - Armstrong RC, Le TQ, Frost EE, Borke RC,and Vana AC. "Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter." J Neurosci. Oct 1;22(19):8574-85
17. 2003 - Frost EE, Nielsen JA, Le TQ, and Armstrong RC. "PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination.“ J Neurobiol. Feb 15;54(3):457-72.
Manuscripts in preparation:
Frost EE, Blaschuk KL, and Armstrong RC. "Initiation of oligodendrocyte progenitor cell migration by a PDGF activated MAP kinase signaling pathway."
1990 - Fan, T.-P.D. & Frost, E.E. “A new in vitro assay for the study of endothelial cell wound repair.” Eur. J. Pharmacol. 183 (5): 1809. (presented at XIth International Congress of Pharmacology, Amsterdam, The Netherlands, 1-6 July 1990)
Frost EE, Blaschuk KL, and Armstrong RC. "Initiation of oligodendrocyte progenitor cell migration by a PDGF activated MAP kinase signaling pathway."