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Brian K. Law, Ph.D.

Assoc. Professor
Phone: (352) 273-9423
Office: R5-210, Academic Research Bldg.

Publications: Search PubMed


Research Interest I:

Cyclin-dependent kinases (Cdks) in mammary tumorigenesis and chromosomal instability, and Cdk regulation by the mTOR and TGFβ pathways

This research involves the use of novel models to understand how the activation of Cdks in the mammary gland causes tumor formation by dysregulation of cell proliferation, and through genetic alterations that result from chromosomal instability. These models also provide systems for testing new therapeutic strategies that include non-ATP competitive Cdk inhibitors discovered in our laboratory, and targeting the upstream signaling pathways, such as the mTOR and TGFβ axes, that stimulate Cdk kinase activity.

Key Publications:

1. Corsino, P., Horenstein, N., Ostrov, D., Rowe, T., Law, M., Barrett, A., Aslanidi, G., Cress, W.D., and Law, B., 2009, A novel class of cyclin-dependent kinase inhibitors identified by molecular docking act through a unique mechanism, J. Biol. Chem. 284, 29945-29955

2. Prasad, R. C., Wang, X. L., Law, B., Davis, B., Green, G., Boone, B., Sims, L., and Law, M., 2009, Identification of Genes, including the Gene Encoding p27Kip1, Regulated by Serine 276 Phosphorylation of the p65 Subunit of NF-?B, Cancer Letters, 275, 139-149

3. Cozar-Castellano, I., Harb, G., Selk, K., Takane, K., Vasavada, R., Sicari, B., Law, B., Zhang, P., Scott, D., Fiaschi-Taesch, N., and Stewart, A., 2008, Lessons from the First Comprehensive Molecular Characterization of Cell Cycle Control in Rodent Insulinoma Cell lines, Diabetes, 57, 3065-3068

4. McConnell, J., Gomez, R., McCorvey, L., Law, B., and Wadzinski, B., 2007, Identification of a PP2A interacting protein that functions as a negative regulator of phosphatase activity in the ATM/ATR signaling pathway, Oncogene, 26, 6021-6030

5. Corsino, P., Davis, B., Law, M., Chytil, A., Forrester, E., Nørgaard, P., Teoh, N., andLaw, B., 2007, Tumors initiated by constitutive Cdk2 activation exhibit TGFβ resistance and acquire paracrine mitogenic stimulation during progression, Cancer Res., 67, 3135-3144

6. Taesch, N., Sicari, B., Ubriani, K., Bigatel, T., Takane, K., Cozar-Castellano, I., Bisello, A., Law, B., and Stewart, A., 2006, Cellular Mechanism Through Which Parathyroid Hormone-Related Protein Induces Proliferation in Arterial Smooth Muscle Cells, Circ Res., 99, 933-942

7. Law, M., Forrester, E., Chytil, A., Corsino, P., Green, G., Davis, B., Rowe, T., andLaw, B., 2006, Rapamycin disrupts Cyclin/Cdk/p21/PCNA complexes and Cyclin D1 reverses rapamycin action by stabilizing these complexes, Cancer Res., 66, 1070-1080

8. Chytil, C., Waltner-Law, M., West, R., Aakre, M., and Law, B., 2004, Construction of a Cyclin D1-Cdk2 fusion protein to model the biological functions of Cyclin D1/Cdk2 Complexes, J. Biol. Chem., 279, 47688-47698.

Research Interest II:

The mechanisms promoting breast cancer invasion and metastasisE-cadherin is the primary barrier preventing the invasion and metastasis of human carcinomas and therefore its function must be abrogated in epithelial cancers for tumor dissemination to occur. E-cadherin expression can be blocked by epigenetic silencing, but our results indicate that loss of E-cadherin protein function is highly prevalent among the most aggressive breast cancers. We have discovered that the protein Cub Domain-Containing Protein 1 (CDCP1) that has been implicated in tumor invasion and metastasis is a novel E-cadherin-associated protein. Ongoing studies focus on determining how CDCP1 controls cell-cell adhesion through its association with Cadherins, Catenins, cytoskeletal proteins, and Matrix Metalloproteinases.

Key Publications:

1. Jahn, S., Law, M., Corsino, P., Parker, N., Pham, K., Davis, B., Lu, J., and Law, B., 2012, An In Vivo Model of Epithelial to Mesenchymal Transition Reveals a Mitogenic Switch, Cancer Letters (In Press)

2. Law M., Corsino P., Jahn SC, Davis B., Chen S., Patel B., Pham K., Lu J., Sheppard B., Nørgaard P., Hong J., Higgins P., Kim J.-S., Luesch H., Law B., 2012, Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms, Oncogene. 2012 Apr 30. doi: 10.1038/onc.2012.138

3. Lin, T., Ponn, A., Hu, X., Law, B., and Lu, J., 2010, Requirement of the Histone Demethylase LSD1 in Snail-mediated Transcriptional repression during Epithelial-Mesenchymal Transition, Oncogene, 29, 4896-4904

4. Law, M., Corsino, P., Parker, N., and Law, B., 2010, Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF?B using in silico molecular docking, Cancer Letters, 291, 217-224

5. Corsino, P., Davis, B., Nørgaard, P., Parker, N., Law, M., Dunn, W., and Law, B., 2008, Mammary Tumors Initiated by Constitutive Cdk2 Activation Contain an Invasive Basal-Like Component, Neoplasia, 10, 1240-1252

6. Ruan Q., Han S., Jiang W., Boulton M., Chen Z., Law B., Cai J., 2011, aB-Crystallin, an Effector of Unfolded Protein Response, Confers Anti-VEGF Resistance to Breast Cancer via Maintenance of Intracrine VEGF in Endothelial Cells, Mol Cancer Res., 9, 1632-43

7. Liu, Y., Salvador, L., Byeon, S., Ying, Y., Kwan, J., Law, B., Hong, J., and Luesch, H., 2010, Anticolon Cancer Activity of Largazole, a Marine-Derived Tunable Histone Deacetylase Inhibitor, JPET, 335, 351-361

8. Laughlin, K., Luo, D., Shaw, G., Warrington, K., Law, B., and Harrison, J., 2009, Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest, Differentiation 78, 35-44

9. Brown, K., Ham, A., Cheng, N., Clark, C., Law, B., Chytil, A., Meller, N., Pietenpol, J., and Moses, H., 2008, Identification of Zizimin1, a Cdc42 GEF, as a Smad2 and Smad3 Associated Protein, J. Cell. Biochem. 105, 596-611

10. Shiou, S., Datta, P., Dhawan, P., Law, B., Yingling, J., and Dixon, D., Beauchamp, R., 2006, Smad4-dependent Regulation of Urokinase Plasminogen Activator Secretion and RNA Stability Associated with Invasiveness by Autocrine and Paracrine Transforming Growth Factor-β, J. Biol. Chem., 281, 33971-33981

11. O’Rear, L., Longobardi, L., Torello, M., Law, B., Moses, H., Chiarelli, F., and Spagnoli, A., 2005, Signaling Cross-talk between Insulin-like Growth Factor Binding Protein-3 (IGFBP3) and Transforming Growth Factor-β (TGFβ), Journal of Molecular Endocrinology, 34, 723-737