Our research is focused on understanding of cancer pathogenesis with a particular attention to expression of phenotypical traits in the context of cell lineage development and cellular interactions with microenvironment. Success of such studies greatly depends on the availability of comprehensively characterized immunocompetent mouse models that accurately mimic human cancers. Therefore, we have established a series of genetically defined mouse models of cancers associated with alterations of p53 and Rb tumor suppressors and their pathways. The rationale for choosing these genes is two-fold: (1) alterations in p53 and Rb and/or their pathways occur in over 80% of all human cancers and (2) multiple functions of p53 and Rb have been extensively described and characterized at the molecular and cellular levels providing an appropriate starting point for our studies. Conventional knock out of the Rb gene leads to embryonic lethality, while mice with a single copy of wild-type Rb or complete lack of p53 succumb to rapidly progressing neoplasms with a limited relevance to major human cancers associated with deficiency of these genes. Thus, mouse models allowing cell type-restricted spontaneous or conditional inactivation of p53 and/or Rb have been either generated by our lab or received from other investigators.

Our main areas of interest include understanding the role of stem cell compartment in carcinogenesis, studies of epithelial ovarian cancer pathogenesis and modeling metastasis. We are also interested in pursuing technology-oriented research based on cross-disciplinary collaborations are described below.

For more information, please visit my homepage.

SELECT PUBLICATIONS

1. Flesken-Nikitin, A., Choi, K.-C., Eng, J. P., Shmidt, E. N. and Nikitin, A. Yu. (2003). Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res., 63: 3459-3463.
2. Zipfel, W. R., Williams, R. M., Christie, R., Nikitin, A. Yu., Hyman, B. T., and Webb, W. W. (2003). Live tissue intrinsic emission microscopy using multiphoton-excited fluorescence and second harmonic generation. Proc. Natl. Acad. Sci. USA, 100: 7075-7080.
3. Manor, D., Shmidt, E. N., Budhu, A., Flesken-Nikitin, A., Zgola, M., Page, R., Nikitin, A. Yu., and Noy, N. (2003). Suppression of mammary tumor growth by cellular retinoic acid binding protein-II. Cancer Res., 63: 4426-4433.
4. Nikitin, A. Yu. , Alcaraz, A., Anver, M., Bronson, R. T., Cardiff, R. D., Dixon, D., Fraire, A. E., Gabrielson, E. W., Gunning, W. T., Haines, D. C., Kaufman, M. H., Linnoila, I., Maronpot, R. R., Rabson, A. S., Reddick, R. L., Rehm, S., Rozengurt, N., Schuller, H. M., Shmidt, E. N., Travis, W. D., Ward, J. M., and Jacks, T. (2004). Classification of proliferative pulmonary lesions of the mouse: Recommendations of the Mouse Models of Human Cancers Consortium. Cancer Res., 64: 2307-2316.
5. Flesken-Nikitin, A., Williams, R. M., Zipfel, W. R., Webb, W.W. and Nikitin, A. Yu. (2005). Use of multiphoton imaging for studying cell migration in the mouse. In: Ed. Guan, J.-L. Methods in Molecular Biology, vol. 294: Cell Migration: Developmental Methods and Protocols. Humana Press Inc., Totowa, NJ. p. 335 - 344.
6. Zhou, Z., Flesken-Nikitin, A., Levine, C. G., Shmidt, E. N., Eng, J. P., Nikitina, E. Yu., Spencer, D. M., and Nikitin, A. Yu. (2005). Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb+/- mice. Cancer Res. 65:787-796.
7. Daikoku, T., Tranguch, S., Trofimova, I. N., Dinulescu, D. M., Jacks, T., Nikitin, A. Yu., Connolly, D. C., and Dey, S. K. (2006). Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res. 66:2527-2531.
8. Zhou, Z., Flesken-Nikitin, A., Corney, D. C., Wang, W., Goodrich, D. W., Roy-Burman, P. and Nikitin, A. Yu. (2006). Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66:7889-7898.
9. Zhou, Z., Flesken-Nikitin, A. and Nikitin, A. Yu. (2007). Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res. 67:5683-5690.
10. Liao, C.-P., Zhong, C., Saribekyan, G., Bading, J., Park, R., Conti, P. S., Moats, R., Berns, A., Shi, W., Zhou, Z., Nikitin, A. Yu., and Roy-Burman, P. (2007). Mouse models of prostate adenocarcinoma with capacity for monitoring spontaneous carcinogenesis by bioluminescence or fluorescence. Cancer Res. 67:7055-7546.
11. Corney, D. C., Flesken-Nikitin, A., Godwin, A. K., Wang, W. and Nikitin, A. Yu. (2007). MicroRNA-34b and -34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433-8438.
12. Flesken-Nikitin, A., Toshkov, I.A., Nascar, J., Tyner, K. M., Williams, R. M., Zipfel, W. R., Giannelis, E., and Nikitin, A. Yu. (2007). Toxicity and biomedical imaging of layered nanohybrids in the mouse. Tox. Pathology 35: 804-810.
13. Choi, J., Burns, A. A., Williams, R. M., Zhou, Z., Flesken-Nikitin, A., Zipfel, R. W., Wiesner, U., and Nikitin, A. Yu. (2007). Core-shell silica nanoparticles as fluorescent biological labels for nanomedicine applications. J. Biomed. Optics 12: 064007.
14. Nikitin, A. Yu., Matoso, A., and Roy-Burman, P. (2007). Prostate stem cells and cancer. Histol. Histopathol. 22: 1043-1049.
15. Matoso, A., Zhou, Z, Hayama, R., Flesken-Nikitin, A. and Nikitin, A. Yu. (2008). Cell lineage-specific genetic interactions between Men1 and Rb in neuroendocrine neoplasia. Carcinogenesis 29:620-628.
16. Xu, X., Page, J.L., Surtees, J.A., Liu, H., Lagedrost, S., Lu, Y., Bronson, R., Alani, E., Nikitin, A. Yu., and Weiss, R.S. (2008). Broad overexpression of ribonucleotide reductase genes in mice specifically induces lung neoplasms. Cancer Res. 68:2652-2660.
17. Antoch, M. P., Gorbacheva, V. Y., Vykhovanets, O., Toshkov, I. A., Kondratov, R. V., Kondratova, A. A., Lee, C., and Nikitin, A. Yu. (2008). Disruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle 7: Epub. 2008/04/18
18. Ince, T. A., Ward, J. M., Valli, V. E., Sgroi, D., Nikitin, A. Yu., Loda, M. F., Griffey, S. M., Crum, C. P., Crawford, J. M., Bronson, R. T., Brayton, C., and Cardiff, R. D. (2008). “Do-it-yourself (DIY) Pathology". Nature Biotechnology. In press.
19. Schug, T. T., Berry, D. C., Toshkov, I. A., Cheng, L., Nikitin, A. Yu., and Noy, N. (2008). Overcoming retinoic acid-resistance of mammary carcinomas by diverting retinoic acid from PPARß/d to RAR. Proc. Natl. Acad. Sci. USA. In press.