Larisa Fedorova, Ph.D.
Faculty Appointment:
Research Assistant Professor
Training:
- M.Sc, Biophysics, Department of Biophysics, Faculty of Biology, Moscow State University,
Russia, June 1982
- Ph.D., Molecular Biology, V.A. Engelhardt Institute of Molecular Biology, Moscow,
Russia, April 2001
Positions Held:
1982-1985 Junior Research Associate Department of Experimental Pathology, Research
Institue for Biological Tests of Chemical Compounds, Kupavna, Moscow region, Russia
1985-1991 Research Associate, Institute of Biotechnology, Moscow, Russia
1991-1997 Research Associate, Laboratory of Isotopic Research, V.A. Engelhardt Institute
of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1999-2003 Research Fellow, Vision Research Laboratories, New England Medical Center,
Tufts University School of Medicine
July 2003-Present Research Assistant Professor, Department of Medicine, University
of Toledo Health Science Campus
Awards and Honors:
Stipend of George Soros Foundation (Biodiversity program), 1993
Research Award from "Fight for Sight - Prevent Blindness America", 2002
Research Experience:
Basic skills:
Protein: Protein isolation and purification using conventional procedures, electrophoresis, two-dimensional electrophoresis, isoelectrofocusing, in gel protein digestion and extraction, Western blotting, analytical centrifugation.
DNA&RNA: Nucleicacid isolation and purification, agarose and acryl-amide gel electorophoresis and gel documentation, Northern and Southern blotting techniques. PCR and RT-PCR. Construction of expression vectors.
Cell Cultures: Preparation and handling of primary cell cultures, maintenance and growth of cell lines, transformation and transfection.
Histology and Cytology: Preparation and handling of cell cultures and tissues for conventional and immunological staining. Cell viability, apoptosis and proliferation assays. Fluorescent and immunoperoxidase staining of cells and tissues. Bright field, DIC, polarized and confocal microscopy. Image acquisition and statistical analysis.
Special skills: Production of transgenic mice, including pronuclei microinjection, analysis and maintaining
transgenic and knockout lines.
Bioinformatics:
Good computer skills including database analysis.
RESEARCH ACTIVITY AND SCIENTIFIC ACHIEVEMENTS:
Dr. Federova came to the Medical College of Ohio in 2003 as a research assistant professor
in the laboratory of Dr. Shapiro and Dr. Malhotra to begin a pilot project "Proteomic
study of kidneys from partially nephrectomized rats immunized against cardiotonic
steroid marinobufagenin." She found that immunization against marinobufagenin attenuated
the severity of fibrosis and oxidative stress seen after partial nephrectomy. This
observation promoted a large investigation into marinobufagenin role in the development
of renal fibrosis. They demonstrated that marinobufagenin induced periglomerular,
perivascular and interstitial fibrosis and provided evidence that marinobufagenin
triggers epithelial to mesenchymal transition through up-regulation and subcellular
relocation of the transcription factor Snail in kidneys and renal epithelial cell
line. Recently she analyzed the Snail expression in pathologies associated with elevated
levels of marinobufagenin, such as preeclampsia and cardiac fibrosis. The expression
of the transcription factor Snail in human and rat placentas was down-regulated by
30-50% in preeclampsia.She also found that the transcription factor Snail is specifically
localized in rat cardiac and renal autonomic nerves and its level remained unchanged
with marinobufagenin infusion.
Since 2007 Dr. Fedorova has worked with Dr. Najjar, the Director of the Center of
Endocrine and Diabetic Research at the University of Toledo, Health Science Campus.
She particularly helped Dr. Najjar in the study of apoptosis, inflammation and fibrosis
in the liver of mice with genetically altered insulin clearance.
Dr. Federova also teaches laboratory work to graduate, medical, and summer students
and residents in Dr. Shapiro and Dr. Malhotra's laboratory. She also consults graduate
students from Dr. Najjar's laboratory for the immunohistochemical analysis of metastasis
development and epithelial to mesenchymal transition.
Before Dr. Federova joined the University of Toledo, she worked at Tuft University
in Boston. She started there in 1999 as a research assistant in the Transgenic Core
Research Laboratory under supervision of Dr. Janis Lem. Upon completion of her Ph.D.
thesis. In 2001 she transferred to the Vision Research Laboratory of Dr. Elizabeth
Fini and began a pilot project "Proteomic analysis of normal and keratoconus corneas"
as a research fellow. At that time she received a post-doctoral fellow grant support
from Fight for Sight To Prevent Blindness America.
Original Publications:
1. Fedorova L.V., Raju V., El-Okdi N., Shidyak A., Kennedy D.J., Vetteth S., Giovannucci D.R., Bagrov A.Y., Fedorova O.V., Shapiro J.I., Malhotra D. The Cardiotonic Steroid Hormone Marinobufagenin Induces Renal Fibrosis. Implication of Epithelial to Mesenchymal Transition. Am J Physiol Renal Physiol. 2009, Apr,296(4):F922-34..
2. Elkareh J., Periyasamy S.M., Shidyak A., Vetteth S., Schroeder J., Raju V., Hariri I.M., El-Okdi N., Gupta S., Fedorova L., Liu J., Fedorova O.V., Kahaleh B.M., Xie Z., Malhotra D., Watson D.K., Bagrov A.Y., Shapiro J.I. Marinobufagenin Induces Increases in Procollagen Expression in a Process Involving Protein Kinase C and Fli-1: Implications for Uremic Cardiomyopathy. Am J Physiol Renal Physiol, 2009,May, 296(5):F1219-26.
3. Lee, S.J., Heinrich, G., Fedorova, L., Al-Share, Q.Y., Ledford, K.J., Fernstrom, M.A., McInerney, M.F., Gatto-Weis, C., and Najjar, S.M. The Insulin Resistant L-SACC1 Mouse: A Novel Model of Non-Alcoholic Steatohepatitis.Gastroenterology 2008 Dec;135(6):2084-95.
4. El-Okdi, N., Smaili, S., Raju, V., Shidyak, A., Gupta, S., Fedorova, L., Elkareh, J., Periyasamy, S., Shapiro, A., Kahaleh, M., Malhotra, D., Xie, Z., Chin, K-V., Shapiro, J. The Effects of Cardiotonic Steroids on Dermal Collagen Synthesis and Wound Healing. J Appl. Physiol. 2008, Jul;105(1):30-6
5. Elkareh J., Kennedy DJ., Yashswi B., Vetteth S., Shidyak a., Kim EG., Smaili S., Periyasami.SM., Hariri IM., Fedorova L., Liu J., Wu L., Kahaleh MB., Xie Z., Malhotra D., Fedorova OV., Kashkin VA., Bagrov AY., Shapiro JI. Marinobufagenin stimulates fibroblast collagen production and causes fibrosis in experimental uremic cardiomyopathy. Hypertension 2007, Jan; 49(1):215-24
6. Kennedy DJ., Vetteth S., Periyasamy SM., Kanj M., Fedorova L., Khouri S., Kahaleh MB, Xie Z, Malhotra D, Kolodkin NI, Lakatta EG, Fedorova OV, Bagrov AY, Shapiro JI. Central role for the cardiotonic steroid, marinobufagenin, in the pathogenesis of experimental uremic cardiomyopathy. Hypertension 2006, Mar 47 (3); 488-95.
7. Fedorov A., Roy S., Fedorova L., Gilbert W. Mystery of intron gain. Genome Research 2003. 13, 2236-2241.
8. Fedorov, A., Saxonov, S., Fedorova, L., Daizadeh, I. Comparison of intron-containing and intron-lacking human genes elucidates putative exonic splicing enchancers. Nucleic Acid Res., 2001, 29 (7): 1464-1469.
9. Fedorova, L.V., Daizadeh, I., Fedorov, A., Ryskov, A.P. In silico genomic DNA restriction analysis reveals fragment non-randomness. Genetika (Russian) 2001, 37 (4): 456-466.
10. Fedorov, A., Fedorova, L., Grechko, V.V., Ryabinin, D., Sheremet'eva, V.A., Bannikova, A.A, Lomov, A.A, Ryskov, A.P, Darevsky, I.S. Variable and invariable DNA repeats characters revealed by taxonprint approach are useful for molecular systematics. J. Mol. Evol. 1999, 48 (1): 69-76.
11. Fedorov, A., Starshenko, V., Fedorova, L., Filatov, V., Grigor'ev, E. Influence of exon duplication and shuffling on intron phase distribution. J. Mol. Evol. 1998, 46 (3): 263-271.
12. Grechko, V.V., Ryabinin, D.M., Fedorova, L., Fedorov, A., Ryskov, A.P., Darevski, I.S. Parentage of Caucasian parthenogenetic rock lizard species (Lacerta) as revealed by restriction endonuclease analysis of highly repetitive DNA. Amphibia-Reptilia, 1997, 18: 407-418.
13. Grechko, V.V., Fedorova, L.V., Fedorov, A.N., Slobodyanyuk, S.Ya., Ryabinin, D.M., Melnikova, M.N., Bannikova, A.A., Lomov, A.A., Sheremet'eva, V.A., Gorshkov, V.A., Sevostyanova, G.A., Semenova, S.K., Ryskov, A.P., Mednikov, B.M., Darevsky, I.S. Restriction endonuclease analysis of highly repetitive DNA as a phylogenetic tool. J. Mol. Evol. 1997, 45 (3): 332-336.
14. Fedorov, A., Suboch, G., Bujakov, M., Fedorova, L. Analysis of nonuniformity in intron phase distribution. Nucleic Acids Res., 1992, 20 (10): 2553-2557.
Reviews, book chapter.
15. Fedorov A., Fedorova L., Where is the difference between the genomes of humans and annelids? Genome Biology., 2006., 7(1):203, 1-2.
16. Fedorova L., Fedorov A. Puzzles of the human genome: why do we need our introns? Current Genomics 2005, Vol 6 (8) ; 589-595.
17. Fedorov A., Fedorova L. 2004. Introns: mighty elements from RNA world. J Mol Evol. 2004 59, 718-721
18. Fedorov A., Fedorova L. Exonic splicing enhancers. 2003 in Encyclopedia of the Human Genome, Nature Publishing Group, London, v 2, 386-391.
19. Fedorova L., Fedorov A Introns in gene evolution. Genetica 2003, 118: 123-131
Publications in internationally regognized Russian journals.
20. Grechko VV, Fedorova LV., Riabinin DM., Riabinina NL., Chobanu DG., Kosushkin SA., Darvskii IS. Molecular markers of nuclear DNA in the study of evolution and speciation process in an example of “Lacerta agilis complex” (Sauria:Lacertidae) (Russian)., Mol Biol., (Mosk). 2006., Jan-Feb., 40 (1):61-73.
21. Bannikova, A.A., Dolgov, V.A., Fedorova, L.V., Fedorov, A.N., Lomov, A.A., Mednikov B.M. Divergence of shrews (Insectivora, Soricidae) from the data of DNA restriction analysis. Zoologichesky zhurnal (Russian), 1996, 75 (2): 256-270.
22. Bannikova, A.A., Dolgov V.A., Fedorova, L.V., Fedorov, A.N., Troitsky, A.V., Lomov, A.A., Mednikov B.M. Taxonomic relationships among hedgehogs of the subfamily Erinaceinae (mammal, Insectivora) determined on the data of restriction-endonuclease analysis of total DNA. Zoologichesky zhurnal (Russian), 1995, 74 (5): 95-106.
23. Bannikova, A.A., Fedorova, L.V., Fedorov, A.N., Troitsky, A.V., Grechko, V.V., Dolgov, V.A., Lomov, A.A., Mednikov, B.M. Comparison of DNA repeats elements of mammals fam. Erinacea using restriction analysis. Genetika (Russian), 1995, 31 (11): 1498-1506.
24. Grechko, V.V., Ryabinin, D.M., Fedorova, L.V., Fedorov, A.N., Darevskii, I.S., Ryskov, A.P. DNA taxonprint analysis of family Lacertidae species. Molecular Biology (Russian), 1993, 27 (6): 883-890.
25. Fedorov, A.N., Grechko, V.V., Slobodyanuck, S.Ya., Fedorova, L.V., Timochina, G.I. Taxonomic analysis of DNA repeated sequences. Molecular Biology (Russian), 1992, 26 (2): 464-469.
26. Reshentiak, V.I., Sheremet, O.K., Fedorova, L.V., Izotov M.V., Devichenskii V.M. Activity of enzymes of xenobiotics metabolism in peripheral blood lymphocytes in man. Vestn Ross Akad Med Nauk. (Russian), 1994, 5: 38-41.
27. Burlakova E.B., Aristarkhova S.A., Fedorova L.V., Sheludchenko N.I., Shishkina L.N. The characteristics of the effect of dipalmitoylphosphatidylcholine and its structural fragments on the lipid peroxidation of biological membranes. Nauchnye Dokl Vyss Shkoly Biol Nauki. (Russian), 1991, 9: 21-7.
ABSTRACTS
Fedorova L., Raju V., Shidyak A., El-Okdi N., El-Kareh J., Haller S., Shapiro JI., Malhotra D. Cardiotonic steroid marinobufagenin induces renal fibrosis through up-regulation of transcription factor Snail. J Am Soc Nephrol. 2008, 19, TH-PO434. Raju V., Malhotra D., Nadour A., Shapiro JI., Fedorova L. Cardiotonic steroids induce epuithelial mesenchymal transformation in a process requiring reactiveoxygen species in LLC-PK1 cells. J Am Soc Nephrol, 2007, SA-PO286. Fedorova L., Raju V., Malhotra D., Liu J., Kennedy DJ., Bagrov AY., Fedorova OV., Zie Z., Shapiro JI. Induction of epithelial mesenchymal transformation (EMT) by the cardiotonic steroid, marinobufagenin, in LLC-PK1 cells. J Am Soc Nephrol, 2006, SA-PO270. Fedorova L., Tamirisa A., Vetteth S., Kennedy DJ., Shapiro JI., Malhotra D. Identification of differentially regulated proteins in the kidney following partial nephrectomy (PNx). J Am Soc Nephrol, 2004, 15, SU-PO622. Vetteth S., Kennedy DJ., Fedorova L., Tamirisa A., Malhotra D., Shapiro JI. Identification of differentially regulated proteins during cardiac hypertrophy following partial nephrectomy (PNx). J Am Soc Nephrol, 2004, 15, SU-PO621.. Fedorova L., Shang F., Wu HK, Ashrafzadesh A., Laver NV., Taylor A., Fini ME., Olson PF. Down-regulation of two proteins in keratoconus revealed by comparative proteomic analysis of human corneal tissue. Ivest. Ophtalmol.Vis. Sci. 2002, 43:E-abstract 3238.