Santosh Kumar, Ph.D.
sbalot@nccs.res.in
Research Areas
Cell Organization and Function, Neuroscience
Education and Experience
Education
Ph.D., Cell Biology, 2011, CSIR - Institute of Microbial Technology, Chandigarh, India
M.Sc., Biotechnology, 2005, Kumaun University Nainital, India.
B.Sc., Biology, 2003, Maharshi Dayanand Saraswati University, Ajmer, India
Research Experience
Scientist D, 2021 to present, National Centre for Cell Science, Pune, India
UGC-Assistant professor, 2019-2021, Department of Biotechnology, Panjab University, Chandigarh, India.
Associate Research Scientist, 2017-2019, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, USA.
Post-doctoral Research Fellow, 2015-2017, Department of Cell Biology, Yale University, New Haven, USA.
Post-doctoral Research Fellow, 2011-2015, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, USA.
Research
Cell Biology and Biochemistry
Research focus
A. Dissecting post-trans-Golgi network protein trafficking in a tractable unicellular system
All cells release proteins and other molecules, and many cell types have evolved specialized pathways to tailor this secretion to particular physiological requirements. A fascinating and medically-important example of such specialization is found in two related structures called lysosome-related organelles (LROs) and dense core granules (DCGs). We have designed experiments that will allow us to better understand the mechanisms used by cells to create LROs/DCGs, particularly focusing on the question of how cells target the appropriate proteins to those structures. An unusual aspect of our proposal is the choice of experimental system. LROs/DCGs have overwhelmingly been studied in animals or animal cells. We propose to pursue our experiments using a single-celled organism called Tetrahymena, which has recently been shown to synthesize secretory organelles LROs/DCGs. Our strategy is designed so that insights gained from our experiments are likely to translate to animal cells, and may thus be useful for better understanding and addressing a large number of human diseases linked to LROs/DCGs including diabetes, cancer, Alzheimer’s, Parkinson's disease and other neurodegenerative congenital disorders.
B. Purification and characterization of signaling protein complexes formed by the major brain G protein, Gαo
How the brain gives rise to thoughts and behaviors remains the greatest unsolved problem in biology. Mental function arises from neurotransmitter signaling, in which one neuron releases a neurotransmitter that binds a specific receptor on another neuron, triggering a response in that target neuron. Signaling by the neurotransmitter serotonin regulates the activities of neurons. Dysregulation of serotonin signaling has been implicated in clinical depression, schizophrenia and other disorders of mental health, however the molecular mechanism(s) responsible for altered signaling are not currently understood. We are investigating the basic mechanisms by which neurons in the brain communicate with each other using G protein mediated signaling pathway, focusing primarily on the Gαo. Gαo is the most abundant G-protein found in brain tissue, controls both development and adult physiology of the brain. However, the downstream effectors for Gαo signaling pathways have not been fully elucidated.
The goal of our research is to identify and characterize downstream effectors for Gαo using transgenic strains of C. elegans that express epitope-tagged Gαo either in wild-type or constitutively-active (Q205L) which immunoprecipitated the G proteins from protein lysates. We will perform mass spectrometry to identify key proteins that bind specifically with activated Gαo. Further, we will confirm interaction between Gαo and its binding partners, both in vitro using purified proteins, and in vivo, using C. elegans genetics to determine the biological functions of any effectors found. Finally, we will determine if these proteins bind preferentially to the activated GTP-bound Gαo protein, and regulate downstream neuronal signaling. If we get positive results with the worm proteins, we will repeat the experiments with the mouse brain proteins to determine if the interaction is conserved.
Our study would help to understand how the G protein is modified, how its function is affected, and how this controls serotonin signaling. The mechanisms of serotonin signaling are highly conserved between C. elegans and humans and the insights made possible by the power of the C. elegans model system should shed light on new details of human serotonin signaling. This may ultimately help us to understand the disease progression in the depressed brain and the possible interventions that can be used to treat it.
Publications
Selected Publications
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Anil Thakur, Sourabh Jain, Anjali Pant, Akanksha Sharma2, Rajiv Kumar, Gajanand Sharma, Neha Singla3, Ashish Suttee, Santosh Kumar, Ravi Pratap Barnwal, O.P. Katare and Gurpal Singh. (2022) Cyclodextrin derivative enhances the Ophthalmic delivery of poorly soluble azithromycin. ACS Omega, 27, 23050–23060. |
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Alisha Khera, Hema K Alajangi, Akhil Khajuria , Ravi P Barnwal, Santosh Kumar, Gurpal Singh. ( 2022) Highlighting the potential role of Exosomes as the targeted nano-therapeutic carrier in metastatic breast cancer. Curr Drug Deliv, PMID:35379150 (Corresponding author) |
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Sapan Borah, Karthigeyan Dhanasekaran, Santosh Kumar (2022). The LEM-ESCRT toolkit: repair and maintenance of the nucleus. Frontier in Cell And Developmental Biology, 10:989217 (Corresponding author) |
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Santosh Kumar*, Chandramohan Chitraju, Robert Farese Jr., Tobias Walther, and Christopher Burd (2021) Conditional targeting of phosphatidylserine decarboxylase to lipid droplets. Biology Open 10, bio058516. (*Co-corresponding author) Impact Factor in 2021: 2.5 |
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Santosh Kumar*, Andrew C. Olson and Michael R. Koelle. (2021) The neural G protein Gαo tagged with GFP at an internal loop is functional in C. elegans. G3 (Bethesda) 11 jkab167 (Corresponding author). Impact Factor in 2021: 2.8 |
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Cassandra Kontur, Santosh Kumar, Xun Lan, Jonathan K. Pritchard and Aaron P. Turkewitz3. (2016) Whole Genome Sequencing Identifies a Novel Factor Required for Secretory Granule Maturation in Tetrahymena thermophila. G3, 6, 2505–2516. (Joint First author). Impact Factor in 2016: 2.00 |
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Santosh Kumar, Joseph S. Briguglio and Aaron P. Turkewitz. (2015) Secretion of polypeptide crystals from Tetrahymena thermophila secretory organelles (mucocysts) depends on processing by a cysteine cathepsin, CTH4. Euk. Cell. 14, 817-833. Impact Factor in 2015: 3.00 |
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Highlighted in “Spotlight” “How To Cock the Trigger (If you Are a Ciliate)” in The Euk. Cell. Impact Factor in 2015: 3.00 |
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Santosh Kumar, Joseph S. Briguglio and Aaron P. Turkewitz. (2014). An aspartyl cathepsin, CTH3, is essential for proprotein processing during secretory granule maturation in Tetrahymena thermophila. Mol. Biol. Cell. 25, 2444-2460. Impact factor in 2014: 4.45 |
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Joseph S. Briguglio, Santosh Kumar and Aaron P. Turkewitz. (2013). Lysosomal sorting receptors are essential for secretory granule biogenesis in Tetrahymena. J. Cell Biol. 203 , 537–550. Impact factor in 2013: 9.70 |
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Navdeep Sheokand, Santosh Kumar, Himanshu Malhotra, Vikas Tillu, Chaaya Iyengar Raje and Manoj Raje. (2013). Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition. BBA- General Subjects. 1830, 3816-3827. (Joint First author). Impact factor in 2013: 4.30 |
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Santosh Kumar, Navdeep Sheokand, Mayur Anant Mhadeshwar, Chaaya Iyengar Raje and Manoj Raje. (2012) Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor. Int J Biochem Cell Biol. 44, 189-199. Impact factor in 2012: 4.00 |
All Publications
Patents
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Ravi Pratap Barnwal, Gurpal Singh, Santosh Kumar, Mandeep Kaur and Akhil Khajuria (2020) Development of aptamer conjugated gold nanoparticle based lateral flow detection kit for vitamin D deficiency. (Under processing for filing provisional patent). |
Funding
DBT- Extramural Research grant
UGC-Start up grant
NCCS Intramural funds.
Lab Members
- Nikhat Firdaus Q. Khan, Technical Officer B
- Sakshi Gangurde, Project Assistant
- Amartya Pal, Junior Research Fellow
- Anisha Atre, Project trainee (July-December 2022)
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Last updated On : 19 October 2022 10:55