Dr. Biplab Dasgupta PhD
Associate Professor of Pediatrics
Cincinnati Children's Hospital, OH, USA
Hangout Title:Understanding Cancer: From Development to Therapy
Hangout Schedule: Jan 15th: 3 pm EST, 2 pm CST, 12 noon PST
Dasgupta Research Lab
Integration of Metabolic and Signaling Pathways
Our lab explores the integration of metabolic and signaling pathways that regulate cancer development and progression. We are interested in elucidating the mechanisms by which cellular metabolism regulates the normal development of the nervous system and how metabolic alterations are linked to nervous system disorders including brain tumors.
We examine cellular energy sensors and metabolic regulators in brain development tumorigenesis including the role of the energy sensor AMPK and the anabolic kinase mTOR. AMP-activated protein kinase (AMPK) is a molecular hub of metabolic control in all eukaryotic cells and functions at the crossroads of several signaling pathways.
We are investigating the context-dependent functions of the AMPK-mTOR signaling axis during normal development and tumorigenesis, why some cancer cells are sensitive while others are resistant to mitochondrial and glycolytic poisons and if this axis provides cellular protection through drug resistance.
Unintended Gene Deletions
Another aim of our laboratory is to investigate the consequence of unintended gene deletions in cancer. Out of the thousands of genes deleted or amplified in human cancer, most are called passengers that occur unintentionally along with driver gene alterations.
We are examining if these unintended alterations that survived negative selection during tumor evolution are critical for tumor biology and can be targeted in a cancer subtype-specific manner.
Links for External, Intrinsic Risk Factors
A third area that we have begun to explore is to understand the molecular links between external and intrinsic risk factors in the etiology of human cancer. Despite strong evidence of substantial contribution of external risk factors to cancer development, the molecular link between specific external factors and specific genetic alterations is a relatively new and highly significant area of investigation.
Our goal is to understand the relationship between external and cell-intrinsic factors that influence cancer incidence, penetrance, development and progression.
Lab Publications
Chhipa RR, Fan Q, Anderson J, Muraleedharan R, Huang Y, Ciraolo G, Chen X, Waclaw R, Chow LM, Khuchua Z, Kofron M, Weirauch MT, Kendler A, McPherson C, Ratner N, Nakano I, Dasgupta N, Komurov K, Dasgupta B. AMP kinase promotes glioblastoma bioenergetics and tumour growth. Nature Cell Biology. 2018 Jul;20(7):823-835.
Sadahiro H, Kang KD, Gibson JT, Minata M, Yu H, Shi J, Chhipa R, Chen Z, Lu S, Simoni Y, Furuta T, Sabit H, Zhang S, Bastola S, Yamaguchi S, Alsheikh H, Komarova S, Wang J, Kim SH, Hambardzumyan D, Lu X, Newell EW, DasGupta B, Nakada M, Lee LJ, Nabors B, Norian LA, Nakano I. Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma. Cancer Research. 2018 Jun 1;78(11):3002-3013.
Dasgupta B, Seibel W. Compound C/Dorsomorphin: Its Use and Misuse as an AMPK Inhibitor. Methods in Molecular Biology. 2018;1732:195-202.
Dasgupta B, Chhipa RR. Evolving Lessons on the Complex Role of AMPK in Normal Physiology and Cancer. Trends Pharmacol Sci. 2016 Mar;37(3):192-206.
Cheng P, Wang J, Waghmare I, Sartini S, Coviello V, Zhang Z, Kim SH, Mohyeldin A, Pavlyukov MS, Minata M, Valentim CL, Chhipa RR, Bhat KP, Dasgupta B, La Motta C, Kango-Singh M, Nakano I. FOXD1-ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells. Cancer Res. 2016 Dec 15;76(24):7219-7230.
Kim SH, Ezhilarasan R, Phillips E, Gallego-Perez D, Sparks A, Taylor D, Ladner K, Furuta T, Sabit H, Chhipa R, Cho JH, Mohyeldin A, Beck S, Kurozumi K, Kuroiwa T, Iwata R, Asai A, Kim J, Sulman EP, Cheng SY, Lee LJ, Nakada M, Guttridge D, DasGupta B, Goidts V, Bhat KP, Nakano I. Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner. Cancer Cell. 2016 Feb 8;29(2):201-13.
Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1-222.
Xiaoli Li, Liang Li, Jie Li, Jared Sipple, Jonathan Schick, Parinda Mehta, Stella Davies, Biplab Dasgupta, Ronald Waclaw, and Qishen Pang. Concomitant inactivation of Foxo3a and Fancc or Fancd2 reveals a two-tier protection from oxidative stress. Antioxidants & Redox Signaling. 2014 Oct 20;21(12):1675-92.
Shabnam Pooya, Xiaona Liu, V.B. Sameer Kumar, Jane Anderson, Fumiyasu Imai, Wujuan Zhang, Georgianne Ciraolo, Nancy Ratner, Kenneth D. R. Setchell, Yoshida Yutaka, Michael P. Jankowski and Biplab Dasgupta*. The Tumor Suppressor LKB1regulates Myelination through Mitochondrial Metabolism. Nature Communications. 2014 Sep 26;5:4993. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Ichiro Nakano and Biplab Dasgupta*. The AMPK inhibitor Compound C is a potent AMPK-independent anti-glioma agent. Molecular Cancer Therapeutics. 2014 Mar;13(3):596-605. *Corresponding author.
Lisa Ehrman, Diana Nardini, Sarah Ehrman, Tilat Rizvi, James Gulick, Maike Krenz, Biplab Dasgupta, Jeffrey Robbins, Nancy Ratner, Masato Nakafuku, and Ronald Waclaw. The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon. Journal of Neuroscience. 2014 Mar 5;34(10):3767-78.
Swagata Karkare, Rishi Raj Chhipa, Jane Anderson, Xiaona Liu, Heather Henry, Anjelika Gasilina, Nicholas Nassar, Jayeeta Roychoudhury, Jason P Clark, Ashish Kumar, Giovanni M. Pauletti, Pradip K Ghosh and Biplab Dasgupta*. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth. Clinical Cancer Research. 2014 Jan 1;20(1):199-212. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Shabnam Pooya, Matthew Wortman, Sara Yachishin, Ashish Kumar, Lionel Chow, Xuan Zhou, Ying Sun, Brian Quinn, Christopher McPherson, Ronald Warnick, Ady Kendler, Sailendra Giri, Jeroen Poels, Koennard Nogra, Benoit Viollet, Gregory A. Grabowski and Biplab Dasgupta*. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proceedings of National Academy of Sciences, USA. 2014 Jan 28;111(4):E435-44. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Shabnam Pooya, Matthew Wortman, Sara Yachishin, Ashish Kumar, Lionel Chow, Xuan Zhou, Ying Sun, Brian Quinn, Christopher McPherson, Ronald Warnick, Adi Kendler, Sailendra Giri, Jeroen Poels, Koennard Nogra, Benoit Viollet, Gregory A. Grabowski and Biplab Dasgupta*. Novel mechanisms of mTOR and cdc25c regulation by AMPK agonists independent of AMPK. Proceedings of National Academy of Sciences, USA. *Corresponding author. Manuscript in Press.
Xiaona Liu, Rishi Raj Chhipa and Biplab Dasgupta*. The Selective AMPK inhibitor Compound C is a potent AMPK-independent anti-glioma agent. Molecular Cancer Therapeutics. *Corresponding author. Manuscript in Press.
Karkare S, Chhipa RR, Anderson J, Liu X, Henry H, Gasilina A, Nassar N, Roychoudhury J, Clark JP, Kumar A, Pauletti GM, Ghosh PK, Dasgupta B*. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth. Clinical Cancer Research. 2013 Oct 31. Epub ahead of print. *Corresponding author.
Biplab Dasgupta*, Ju Jeong Sun, Jason Gustin, Su-Ryun Jung, Kazuhiko Higasida and Jeffrey Milbrandt. The AMPK β2 subunit is required for energy homeostasis during metabolic stress. Mol Cell Biol. 2012 Jul;32(14):2837-48. Cover article. PMID: 22586267. *Corresponding author.
Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in Neurons. Proceedings of National Academy of Sciences,USA. 104:7217-22. 2007.
Revollo JR, Korner A, Mills K, Satoh A, Wang T, Garten A, Dasgupta B, Townsend R, Wolberger C, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metabolism.6:363-75. 2007.
Hegedus B, Dasgupta B, Eun Shin J, Emnett RJ, Hart-Mahon EK, Elghazi L, Bernal-Mizrachi E, Gutmann DH. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell. 1:443-457. 2007.
Dasgupta B, Gutman DH. Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. Journal of Neuroscience. 25: 5584-5594. 2005.
Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res. 2005 Apr 1;65(7):2755-60.
Dasgupta B, Li W, Perry A, Gutmann DH. Glioma formation in Neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Research. 65: 236-245. 2005.
