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Biomedical Sciences
Alexander Nikitin
MD, PhD
Professor of Pathology
Leader, Cornell Stem Cell Program


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Phone: 607 253 4347
Fax: 607 253 4212
E-mail: an58@cornell.edu
RESEARCH

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.

SELECTED 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. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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 PPARβ/δ to RAR. Proc. Natl. Acad. Sci. USA. 105:7546-7551.
  8. Kaufman M. H., Nikitin, A. Yu., and Sundberg, J. P. (2010). Histologic Basis of Mouse Endocrine System Development: A Comparative Analysis. CRC Press. Boca Raton, FL., 232 p.
  9. Corney, D. C., Hwang, C., Matoso, A., Vogt, M., Flesken-Nikitin, A., Godwin, A. K., Kamat, A. A., Sood, A. K., Hermeking, H., , Ellenson, L., H., and Nikitin, A. Yu. (2010). Frequent downregulation of miR-34 family in human ovarian cancers. Clin. Cancer Res. 16: 1119–1128.
  10. Williams, R. M., Flesken-Nikitin, A., Ellenson, L. H., Connolly, D. C., Hamilton, T. C., Nikitin, A. Yu., and Zipfel, W. R. (2010). Strategies for high resolution imaging of epithelial ovarian cancer by laparoscopic nonlinear microscopy. Translational Oncology. 3:181-194.
  11. Cheng, L., Zhou, Z., Flesken-Nikitin, A., Toshkov, I. A., Wang, W., Camps, J., Ried, T. and Nikitin, A. Yu. (2010). Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency. Oncogene 29:5700-5071.
  12. Liu, K., Cheng, L., Flesken-Nikitin, A., Huang, L., Nikitin, A. Yu., and Pauli, B. U. (2010). Conditional knockout of fibronectin abrogates mouse mammary gland lobulo-alveolar differentiation. Developmental Biology 6:11-24.
  13. Choi, J., Curtis, S., Roy, D. M., Flesken-Nikitin, A., and Nikitin, A. Yu. (2010). Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency. Am. J. Pathology. 177:2645-2658.
  14. Sun, H., Wang, Y., Chinnam, M., Zhang, X., Hayward, S. W., Fosrter, B. A., NIkitin, A. Yu., Willis, M., and Goodrich, D. W. (2011). An E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo. Proc. Natl. Acad. Sci. USA. 108:704-709.

     

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