Dissection of eukaryotic cell signaling pathways.
Summary of Research:
We are interested in dissection of signaling pathways in two diverse organisms: malaria parasite Plasmodium falciparum and mammalian neurons.
I. Dissection of intracellular signaling and trafficking cascades of Plasmodium falciparum.
We are interested in delineating novel signaling and trafficking cascades in Plasmodium, which may unravel novel molecular mechanisms involved in the development of the malaria parasite. The role of second messengers like calcium, phosphoinsotides and cAMP and their effectors in the regulation of signaling cascades is of specific interest. Our findings have shed light on molecular and cellular mechanisms involved in the regulation of key signaling proteins from the parasite and provided insights into novel signaling and trafficking cascades, which may be relevant to key events like host cell invasion and hemoglobin trafficking.
II. Characterization of novel signaling pathways in neuronal apoptosis.
Neurons undergo apoptosis during nervous system development and during neurodegeneration. A subset of terminally differentiated neurons exhibits signs of cell cycle re-entry, which results in their apoptosis. We are interested in delineating molecular mechanisms involved in Cell cycle Related Neuronal Apoptosis (CRNA), which are poorly understood. We are interested in understanding how cell cycle related proteins like cyclins and cyclin dependent kinases control neuronal apoptosis? Recent studies from our laboratory have led to the identification of novel mechanisms via which cyclin D1 may be regulated during CRNA and in turn contribute to this process.
Manoj Kumar, Anuj Tripathi, Priyanka Bansal, Roseleen Ekka, Monika Chauhan, Disha Chauhan, Ankit Gupta
• Senior Research Fellow, The Wellcome Trust, UK (2002)
• Swarnajayanti Fellowship (2008)
• National Bioscience Award (2008)
• Fellow of the National Academy of Science India
• Fellow of Indian National Science Academy
• Shanti Swarup Bhatnagar Award in Medicine (2013)
• J.C. Bose National Fellowship (2017)
- Ranjana Maurya#, Anuj Tripathi#, Manish Kumar, Neelam Antil, Yoshiki Yamaryo-Botté, Praveen Kumar, Priyanka Bansal, Christian Doerig, Cyrille Y. Botté$, T.S. Keshava Prasad$ and Pushkar Sharma$,* (2021). PI4-kinase and PfCDPK7 signaling regulate phospholipid biosynthesis in P. falciparum. EMBO Reports Dec 6;e54022. doi: 10.15252/embr.202154022 #,$equal contributors
- Priyanka Bansal, Neelam Antil, Manish Kumar, Yoshiki Yamaryo-Botté, Rahul Singh Rawat, Sneha Pinto, Keshava K. Datta, Nicholas J. Katris, Cyrille Y. Botté#, T.S. Keshava Prasad# and Pushkar Sharma#,* (2021). Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. Plos Pathogens 17(2):e1009325. doi: 10.1371/journal.ppat.1009325. eCollection 2021 Feb #equal contributors
- Roseleen Ekka, Ankit Gupta, Sonika Bhatnagar, Pawan Malhotra, Pushkar Sharma* (2020). Phosphorylation of rhoptry protein RhopH3 is critical for host cell invasion by the malaria parasite mBio. 11(5):e00166-20. doi: 10.1128/mBio.00166-20.
- Monika Chauhan, Prashant Modi and Pushkar Sharma* (2020). Aberrant activation of neuronal cell cycle caused by dysregulation of ubiquitin ligase Itch results in neurodegeneration. Cell Death & Disease Jun 8;11(6):441. doi: 10.1038/s41419-020-2647-1.
- Priyanka Bansal, Anuj Tripathi, Vandana Thakur, Asif Mohmmed, and Pushkar Sharma* (2017) Autophagy Related Protein ATG18 regulates apicoplast biogenesis in Apicomplexan parasites. mBio 8(5). pii: e01468-17. doi: 10.1128/mBio.01468-17.
- Sudhir Kumar, Manish Kumar, Roseleen Ekka, Jeffrey D. Dvorin, Aditya S. Paul, Anil K. Madugundu, Tim Gilberger, Harsha Gowda, Manoj T. Duraisingh, T.S. Keshava Prasadand, Pushkar Sharma* (2017). PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum. Nature Communications. 8(1):63. doi: 10.1038/s41467-017-00053-1
- Surbhi Jaiswal and Pushkar Sharma* (2017). Role and regulation of p27 in neuronal apoptosis. Journal of Neurochem.140(4):576-588.
- Prashant Kumar Modi, Surbhi Jaiswal and Pushkar Sharma* (2015) Regulation of Neuronal Cell Cycle and Apoptosis by miR-34a. Mol Cell Biol. 36(1):84-94.
- Praveen Kumar, Anuj Tripati, Ravikant Ranjan, Jean Halbert, Tim Gilberger, Christian Doerig and Pushkar Sharma* (2014). Regulation of Plasmodium falciparum Development by Calcium-dependent Protein Kinase 7 (PfCDPK7). J. Biol. Chem. 289(29):20386-20395.
- Prashant K. Modi, Narayan Komaravelli, Neha Singh, Pushkar Sharma* (2012). Interplay between MEK-ERK signaling, cyclin D1 and cyclin dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons. Mol Biol Cell. 23:3722-30. (Recommended by the faculty of 1000)
- Anwar Ahmed, Kavita Gaadhe, Guru Prasad Sharma, Narendra Kumar, Mirela Neculai, Raymond Hui, Debasisa Mohanty, and Pushkar Sharma* (2012). Novel insights into the regulation of malarial Calcium Dependent Protein Kinase 1. FASEB J. 26(8):3212-21.
- Lev Solyakov, Jean Halbert, Mahmood M. Alam, Jean-Philippe Semblat, Dominique Dorin-Semblat, Luc Reininger, Andrew R. Bottrill, Sharad Mistry, Abdirhaman Abdi, Clare Fennell, Zoe Holland, Claudia Demarta, Yvan Bouza, Audrey Sicard, Marie-Paule Nivez, Sylvain Eschenlauer, Tenzing Lama, Divya Catherine Thomas, Pushkar Sharma, Shruti Agarwal, Selina Kern, Gabriele Pradel, Michele Graciotti, Andrew B. Tobin and Christian Doerig (2011). Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum. Nat Commun. ;2:565. doi: 10.1038/ncomms1558
- Aparna Dixit, Prashant Kumar Singh, Guru Prasad Sharma, Pawan Malhotra, Pushkar Sharma* (2010). PfSRPK1, a novel splicing-related kinase from Plasmodium falciparum. J. Biol Chem. 285(49):38315-23.
- Ankush Vaid, Ravikant Ranjan, Wynand Smythe, Heinrich Hoppe, Pushkar Sharma* (2010). PfPI3K, a Phosphatidylinositol-3 kinase from Plasmodium falciparum, is exported to the host erythrocyte and is involved in hemoglobin trafficking. Blood. 115: 2500-2507. (Recommended by the faculty of 1000)
- Ravikant Ranjan, Anwar Ahmed, Samudrala Gourinath, and Pushkar Sharma* (2009). Dissection of mechanisms involved in the regulation of Plasmodium falciparum calcium dependent protein kinase 4 (PfCDPK4). J. Biol. Chem. 284 (22): 15267-15276.
- Ankush Vaid, Divya C. Thomas and Pushkar Sharma* (2008). Role of Ca2+/Calmodulin-PfPKB pathway in erythrocyte invasion by Plasmodium falciparum. J. Biol Chem 283 (9): 5589-5597.
- Michael T. McIntosh*, Ankush Vaid, Dean H. Hosgood, Justin Vijay, Anindita Bhattacharya, Mayurbhai Sahani, Pavlina Baevova, Keith A. Joiner, and Pushkar Sharma* (2007). Traffic to the malaria parasite food vacuole: Identification of a novel pathway involving a PI3P binding protein. J Biol. Chem. 282(15):11499-508. (Recommended by the faculty of 1000)
- Ankush Vaid and Pushkar Sharma* (2006). PfPKB, a protein kinase B-like enzyme from Plasmodium falciparum: II. Identification of calcium/calmodulin as its upstream activator and dissection of a novel signaling pathway. J Biol. Chem. 281, 27126-27133.
- Amit Kumar, Ankush Vaid, Chiang Syin and Pushkar Sharma* (2004). PfPKB, a novel protein kinase B-like enzyme from Plasmodium falciparum: I.Identification, characterization, and possible role in parasite development. J Biol Chem.;279(23):24255-64.
(* denotes Corresponding author)