Olga Cabello, Ph.D.

Associate Professor 

College                                   Universidad Iberoamericana, A.C., Mexico, D.F.

                                                B.S.  Biomedical Engineering

Graduate School                     Baylor College of Medicine, Houston, TX

                                                Doctorate in Philosophy

                                                Department of Molecular Physiology and Biophysics,

Postdoctoral Fellow                Baylor College of Medicine, Houston, TX

Department of Cell Biology

Laboratory of Dr. Lutz Birnbaumer

Postdoctoral Fellow                Baylor College of Medicine, Houston, TX

                                                Department of Molecular and Human Genetics

                                                Laboratory of Dr. John W. Belmont

PREVIOUS POSITION:

ASSISTANT PROFESSOR,

Department of Molecular and Cellular Biology

Baylor College of Medicine

Houston, Texas

Research Interests

My laboratory recently moved from Baylor College of Medicine to ETSU where I have continued our research program studying embryonic development in the mouse. Traditionally, developmental biology labs have focused on the study of the signaling pathways that coordinate the interaction among distinct cell types and dictate differentiation programs through embryonic life. Our general interest is in understanding how cells respond to intercellular signals through the establishment of functional polarity, shape changes and cell movement and how these events orchestrate organogenesis. Our strategy is to use a combination of molecular genetic, cell biological and biochemical techniques to study mutations in mice that affect these mechanisms and that result in observable birth defects. In most cases, these mutant mice are models of specific human congenital diseases and their study contributes to the understanding of these disorders and to the development of therapeutic interventions. We are particularly interested in studying the development of the various segments of the urinary tract.

We are currently analyzing mouse models of two of the most commonly seen congenital malformations in children, polycystic kidney disease (inv mice) and vesicoureteral reflux (VUR) (Tbx18 mutant mice). In addition to polycystic kidney disease, inv mice have complete reversal or organ laterality (situs inversus), and hepato-biliary and cerebellar malformations. We are specifically interested in the role of inv in the establishment of planar cell polarity through the regulation of the wnt signaling pathway.

We are also studying two transgenic mouse models of retinal diseases: retinal degeneration and retinoblastoma. Retinoblastoma is the most common ocular malignancy in children and results from the inactivation of the Rb gene in retinoblasts during eye development. Retinoblasts are actively proliferating cells, and therefore, inactivation of Rb which known to control the entry into the cell cycle would not be predicted to lead to tumorigenesis in these cells. Therefore, we predict that Rb plays an additional role the establishment of cell polarity in early retinal development and that loss of this second function is the cause of retinoblast transformation.

A third ongoing line of research in my lab is the development of reproducible enabling strategies to manipulate gene expression in vivo in the mouse through the use of RNAi and targeted transcriptional gene silencing. Our lab has received support from the NIH and the March of Dimes Foundation.

We have extensive collaborations with multiple laboratories including with Dr. Paul A. Overbeek, at Baylor College of Medicine, Dr. Mark Majesky at UNC Chapel Hill, Dr. Kathryn Millen at the University of Chicago, and with the Division of Cancer Research at Abbott Laboratories.

References

1.              Schilling W.P., Cabello O.A. and Rajan L. (1992): Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca²⁺ store in vascular endothelial cells activates the agonist-sensitive Ca²⁺-influx pathway. Biochemical. J. 284:521-530.

2.              Cabello, O.A. and Schilling, W.P. (1993): Vectorial Ca²⁺ flux from the extracellular space to the endoplasmic reticulum via a restricted cytoplasmic compartment regulates inositol 1,4,5-trisphosphate-stimulated Ca²⁺ release from internal stores in vascular endothelial cells. Biochemical J. 295: 357-366.

3.              Cabello, O.A. and Schilling, W.P. (1994): "Calcium signaling in endothelial cells". In: International Symposium on Functionality of Endothelium in Health and Disease. Rubio, R. and Pastelin, G., Eds. 139-163. Mexico.

4.              Henry, P.D., Cabello, O.A. and Chen, C.H. (1995): Hypercholesterolemia and endothelial dysfunction (Review). Current Opinion in Lipidology 6(4): 190-5.

5.              Oraevsky, A., Cabello, O.A. Shan, Q., Tittel, F.K. and Henry, P.D. (1994): Detection of Calcium activity in human monocytes by the fura-2 fluorescence method: in vitro differentiation sensitizes cells to dihydropyridine calcium channel modulators. SPIE 2130:

6.              Henry, P.D. and Cabello, O.A. (1995): Vasoprotection and Antihypertensive Therapy (Review). Current Opinion in Nephrology and Hypertension 4(2): 197-200.

7.              Qin, N., Olcese, R., Zhou, J., Cabello, O.A., Birnbaumer, L., and Stefani, E. (1996): Identification of a second region of the b subunit involved in regulation of calcium channel inactivation. Am. J. Physiol  271 (40): C1539 -1545.

8.              Cabello, O.A., Bhat, M., Bellen, H.J., and Belmont, J.W. (1997): Localization of BRRN-1, the human homologue of D. melanogaster barr to 2q11.2.  Genomics 46: 311-313.

9.              Cabello, O.A., Brinkley, B.R., and Belmont, J.W. (1997): Genomic Instability and the mechanisms of chromatid separation in mammalian cells. Molecular Genetics and Metabolism. 65, 105-112.

10.            Ouspenski, I.I., Cabello, O.A., and Brinkley, B.R. (2000): Chromosome condensation factor Brn1p is required for chromatid separation in mitosis. Mol. Biol. Cell 2000 11: 1305-1313.

11.            Cabello, O.A., Eliseeva, E., Youssoufian, H., Plon, S., Brinkley, B.R., and Belmont, J.W. (2001): Cell cycle-dependent expression and nucleolar localization of HCAP-H, -C and -E. Mol. Biol. Cell 12: 3527-3537.

12.            Phillips CL, Miller KJ, Filson, AJ, Nürnberger J, Clendenon JL, Cook G, Dunn KW, Cabello OA, Overbeek PA, Gattone VH, Bacallao RL: Renal cysts of inv/inv mice resemble early infantile nephronophthisis. (2004) Phillips et al., J Am Soc Nephrol 15 (7) 1744-1755. Erratum in J Am Soc Neprhol 15 (12).

13.            Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G (2005): Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet. 37 (5):537-43.

14.          Cabello OA, Ledlie, M., Mules, E., Lopez, J., Seabra, M., Srhimpton, C., Steinkievicz, P., Harrison, W. and Overbeek, P.A. Transgenic rescue of the gunmetal phenotype. Manuscript in preparation.

15.          Cabello OA,Xia X., Chen Q., Overbeek P.A. Retinal cell death induced by overexpression of Oncostatin M. Manuscript in preparation.