Radiation and Cancer Biology
Dipankar Ray, PhD
Assistant Professor in Radiation and Cancer Biology
My laboratory has two major research interests: (1) Understanding the roles of Tumor Necrosis Factor (TNF)-α and Transforming Growth Factor (TGF)-β1 in radiation-induced lung toxicity and further develop a strategy of lung radioprotection. (2) Exploring protein ubiquitination machinery to target oncogenes including epidermal growth factor receptor (EGFR) and mutant KRAS.
- Radiotherapy in the treatment of thoracic cancers including lung cancer is restricted mainly due to the lung toxicity arises post-treatment. The main goal of this research project is to better understand the molecular regulators involved in radiation-induced lung toxicity and to develop agents that can provide lung protection during radiotherapy and radio-chemotherapy. More specifically the current project is focused on improving our understanding about the involvements of TNF-α and TGF-β1 in radiation-induced lung toxicity and to develop strategies, which can block both the signaling pathways with expected better protection during cancer radio-chemotherapy.
- Accumulation of oncogene-specific activating mutation undoubtedly plays a key role not only in cancer initiation and progression, but in many occasions further promote drug resistance. In our laboratory we focus on studying the activating mutations of two important oncogenes: epidermal growth factor receptor (EGFR) and mutant KRAS. Recently, we have obtained data that ubiquitinations of certain EGFR mutants alter its protein stability, which may be associated with drug resistance. Similarly, in case of mutant KRAS, ubiquitination plays critical roles in maintaining its protein stability and GTPase activity. Our long-term objective is to identify the ubiquitination machinery involved in maintaining mutant oncogene protein stability and further develop novel strategies via targeting ubiquitination machinery to induce EGFR/KRAS degradation to kill such oncogene-addicted cancer cells.
Ray Lab Members
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- Zou X, Tsutsui T, Ray Dipankar, Blomquist JF, Ichijo H, Ucker DS, Kiyokawa H: The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. Mol. Cell. Biol. 21(14): 4818-4828, 2001. PM11416155
- Zou X, Ray Dipankar, Aziyu A, Christov K, Boiko AD, Gudkov AV, Kiyokawa H: Cdk4 disruption renders primary mouse cells resistant to oncogenic transformation, leading to Arf/p53-independent senescence. Genes Dev. 16(22): 2923-2934, 2002. PM12435633
- Ray Dipankar, Terao Yasuhisa, Nimbalkar Dipali, Chu Li-Hao, Donzelli Maddalena, Tsutsui Tateki, Zou Xianghong, Ghosh Asish K, Varga John, Draetta Giulio F, Kiyokawa Hiroaki: Transforming growth factor beta facilitates beta-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner. Mol. Cell. Biol. 25(8): 3338-47, 2005. PM15798217
- Ray Dipankar, Osmundson Evan C, Kiyokawa Hiroaki: Constitutive and UV-induced fibronectin degradation is a ubiquitination-dependent process controlled by beta-TrCP. J. Biol. Chem. 281(32): 23060-5, 2006. PM16757476
- Ray Dipankar, Terao Yasuhisa, Fuhrken Peter G, Ma Zhi-Qing, DeMayo Francesco J, Christov Konstantin, Heerema Nyla A, Franks Roberta, Tsai Sophia Y, Papoutsakis Eleftherios T, Kiyokawa Hiroaki: Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. Cancer Res. 67(3): 984-91, 2007. PM17283130
- Ray Dipankar, Terao Yasuhisa, Nimbalkar Dipali, Hirai Hiroyuki, Osmundson Evan C, Zou Xianghong, Franks Roberta, Christov Konstantin, Kiyokawa Hiroaki: Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice. Cancer Res. 67(14): 6605-11, 2007. PM17638870
- Ray Dipankar, Kiyokawa Hiroaki: CDC25A levels determine the balance of proliferation and checkpoint response. Cell Cycle 6(24): 3039-42, 2007. PM18073536
- Ray Dipankar, Kiyokawa Hiroaki: CDC25A phosphatase: a rate-limiting oncogene that determines genomic stability. Cancer Res. 68(5): 1251-3, 2008. PM18316586/PMC-
- Osmundson Evan C, Ray Dipankar, Moore Finola E, Gao Qingshen, Thomsen Gerald H, Kiyokawa Hiroaki: The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint. J. Cell Biol. 183(2): 267-77, 2008. PM18852296/PMC2568023
- Kiyokawa H, Ray Dipankar: In vivo roles of CDC25 phosphatases: biological insight into the anti-cancer therapeutic targets. Anticancer Agents Med Chem 8(8): 832-836, 2008. PM19075565/PMC2753225
- Osmundson Evan C, Ray Dipankar, Moore Finola E, Kiyokawa Hiroaki: Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis. Cell Division 4: 14, 2009. PM19583833/PMC2714307
- Moore Finola E, Osmundson Evan C, Koblinski Jennifer, Pugacheva Elena, Golemis Erica A, Ray Dipankar, Kiyokawa Hiroaki: The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation. Cell Division 5: 22, 2010. PM20825672/PMC2941750
- Ray Dipankar, Terao Y, Christov K, Kaldis P, Kiyokawa H: Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis. Neoplasia (New York, N.Y.) 13(5): 439-44, 2011. PM21532884
- Ray Dipankar, Ahsan A, Helman A, Chen G, Hegde A, Gurjar SR, Zhao L, Kiyokawa H, Beer DG, Lawrence TS, Nyati MK: Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2. Neoplasia 13(7): 570-578, 2011. PM21750651
- Nyati S, Schinske K, Ray Dipankar, Nyati MK, Nyati M, Ross BD, Rehemtulla A: Molecular Imaging of TGFβ-Induced Smad2/3 Phosphorylation Reveals a Role for Receptor Tyrosine Kinases in Modulating TGFβ Signaling. Clin. Cancer Res. 17(23): 7424-7439, 2011. PM21948232
- Ahsan A, Ramanand SG, Whitehead C, Hiniker SM, Rehemtulla A, Pratt WB, Jolly S, Gouveia C, Truong K, Van Waes C, Ray Dipankar, Lawrence TS, Nyati MK: Wild-type EGFR Is Stabilized by Direct Interaction with HSP90 in Cancer Cells and Tumors. Neoplasia 14(8): 670-677, 2012. PM22952420
- Ray Dipankar, Shukla S, Allam US, Helman A, Ramanand SG, Tran L, Bassetti M, Krishnamurthy PM, Rumschlag M, Paulsen MT, Sun L, Shanley TP, Ljungman M, Nyati MK, Zhang M, Lawrence TS: Tristetraprolin mediates radiation-induced TNF-a production in lung macrophages Plos One 8(2): e57290, 2013.
- Ahsan A, Ray Dipankar, Ramanand SG, Hegde A, Whitehead C, Rehemtulla A, Morishima Y, Pratt WB, Osawa Y, Lawrence TS, Nyati MK: Destabilization of the Epidermal Growth Factor Receptor (EGFR) by a Peptide that Inhibits EGFR Binding to Hsp90 and Receptor Dimerization. The Journal of Biological Chemistry: 2013. PM23897823