Education and Training
St. Xavier’s College, Mumbai, India, B.S., Life Sciences, 1995 – 1998
Mumbai University, Mumbai, India, M.S., Life Sciences and Biotechnology, 1998 – 2000
Texas A&M University, College Station, Texas, Ph.D. Genetics, 2000 – 2006
U.T. M.D. Anderson Cancer Center, Smithville, Texas, Post-doctoral training, 2006 – 2011
The American Cancer Society has identified kidney cancer as one of the top 10 most common cancers affecting both males and females. In 2011 alone, more than 60,000 individuals will be diagnosed with kidney cancer, and almost 13,000 of these patients will die as a result. Renal cell carcinoma (RCC) accounts for 85% of kidney cancers, with mutations in the tumor suppressor, Von Hippel-Lindau (VHL) gene, being the most common cause of clear cell renal cell carcinoma (ccRCC). Accumulating evidence suggests that mutations leading to loss of heterozygosity (LOH) and/or tumor suppressor gene function while essential are not sufficient to drive disease progression. The additional early events that drive formation of kidney cancer are as yet elusive. The focus of my research is to understand these early events that trigger tumorigenesis as a critical aspect in understanding the etiology of RCC.
In several renal diseases, including VHL, cysts develop, often as preneoplastic lesions, following loss of gene function. These cysts display a proliferative phenotype and exhibit defects in regulation of key signaling pathways. One of the hallmarks of renal cysts is dysfunctional primary cilia. Primary cilia are hair-like organelles that arise from the apical surface of most cells. In the kidney, the primary cilium acts as a chemo-, osmotic- and mechano-sensor, to regulate cellular signaling pathways. VHL has been shown to localize to the primary cilium, and loss of VHL is associated with absence of primary cilia.
The laboratory is currently elucidating signaling pathways that lead to the destabilization and lack of primary cilia in the setting of VHL-deficiency, using both in vitro and in vivo models. In addition, we are also involved in understanding the cellular consequences resulting from absence of primary cilia. Planar cell polarity (PCP) is a highly regulated and well-orchestrated event in kidney development, and regeneration/repair in response to renal injury. We are currently investigating the consequences of loss of primary cilia, resulting from mutations in VHL, on PCP in response to renal injury. Moreover, we are examining how lack of primary cilia could further effect genomic instability arising from an un-coupling of the cilia-centrosome cycle from the cell cycle. Understanding these early events that trigger formation of preneoplastic renal lesions in patients susceptible to RCC, will provide targets for future therapeutic intervention.
Napierala M, Dere R. Vetcher AA and Wells RD (2004) Structure-dependent Recombination Hotspot Activity of GAA•TTC Sequences from Intron 1 of the Friedreich Ataxia Gene. J. Biol. Chem. 279(8): 6444 – 6454
Dere R, Napierala M, Ranum LPW and Wells RD (2004) Hairpin Structure-forming Propensity of the (CCTG•CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2. J. Biol. Chem. 279(40): 41715 – 41726
Wells RD, Dere R, Hebert ML, Napierala M, and Son LS (2005) Advances in Mechanisms of Genetic Instability Related to Hereditary Neurological Diseases. Nucleic Acids Res. 33(12): 3785 – 3798
Dere R and Wells RD (CCTG•CAGG) Repeats are Crossover Hotspots that are More Prone to Expansions than the DM1 CTG•CAG Repeats in Escherichia coli. J. Mol. Biol. 360: 21 – 36
Short JD, Houston KD, Dere R, Cai SL, Kim J, Johnson CL, Broaddus RR, Shen J, Miyamoto S, Tamanoi F, Kwiatkowski D, Mills GB, and Walker CL (2008) AMP-activated protein kinase signaling results in cytoplasmic sequestration of p27. Cancer Res. 68(16): 6496-506.
Short JD, Dere R, Houston KD, Cai SL, Kim J, Bergeron JM, Shen J, Liang J, Bedford MT, Mills GB, and Walker CL (2010) AMPK-mediated phosphorylation of murine p27 at T197 promotes binding of 14-3-3 proteins and increases p27 stability. Molecular Carcinogenesis 49(5): 429-39.
Dere R, Wilson PD, Sandford R, Walker CL (2010) Carboxy Terminal Tail of Polycystin-1 Regulates Localization of TSC2 to Repress mTOR. PLoS ONE 5(2): e9239.
Bawa-Khalfe T, Lu LS, Zuo Y, Huang C, Dere R, Lin FM, Yeh ET (2012) Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition. PNAS 109(43): 17466-71
Zhang J, Kim J, Alexander A, Cai S, Tripathi DN, Dere R, Tee AR, Tait-Mulder J, Nardo AD, Han JM, Kwiatkowski E, Dunlop EA, Dodd KM, Folkerth RD, Faust PL, Kastan MB, Sahin M, Walker CL (2013) A TSC signaling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nat Cell Biol. 15(10):1186-1196.
Dere R, Perkins AL, Bawa-Khalfe T, Jonasch D, Walker CL (2015) β-Catenin Links von Hippel-Lindau to Aurora Kinase A and Loss of Primary Cilia in Renal Cell Carcinoma. J Am Soc Nephrol. 26(3):553-564.
Zhang J, Tripathi DN, Jing J, Alexander A, Kim J, Powell RT, Dere R, Tait-Mulder J, Lee JH, Paull TT, Pandita RK, Charaka VK, Pandita TK, Kastan MB, Walker CL. (2015) ATM functions at the peroxisome to induce pexophagy in response to ROS. Nature Cell Biology. doi: 10.1038/ncb3230 (In Press).
R. Dere, M. Hebert and M. Napierala (2006) Involvement of Genetic Recombination in Microsatellite Instability. In Wells, R. D. and Ashizawa, T. (eds.) Genetic Instabilities and Hereditary Neurological Diseases, Volume 2, Elsevier-Academic Press, Inc.,