Scientist Profile

Santosh Kumar, Ph.D.

Email

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. o 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    All Publications    Patents

Selected Publications

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

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

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

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
Highlighted in “Spotlight” “How To Cock the Trigger (If you Are a Ciliate)” in The Euk. Cell. Impact Factor in 2015: 3.00

Highlighted in “Spotlight” “How To Cock the Trigger (If you Are a Ciliate)” in The Euk. Cell. Impact Factor in 2015: 3.00

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

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
Highlighted in Nature Reviews Molecular Cell Biology 14, 751 (2013) “A sortilin for secretory granules”. Impact factor in 2013: 36.00
Highlighted in “In Focus” “Sortilins get a new delivery route” in The Journal of Cell Biology. Impact factor in 2013: 9.70
Accepted for cover image in The journal of Cell Biology. Impact factor in 2013: 9.70

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

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

1. Mandeep Kaur, Akanksha Sharma, Gurpal Singh, Santosh Kumar, Ravi P Barnwal. (2021). Architectural and functional details of CF IA proteins involved in yeast 3'-end pre-mRNA processing and its significance for eukaryotes: A concise review. Int J Biol Macromol. 193, 387-400. Impact factor in 2021: 6.9

2. 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

3. 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

4. Gurpal Singh, Harinder Kaur, Akanksha Sharma, Joga Singh, Santosh Kumar, Neha Singla, Indu Pal Kaur, Ravi Pratap Barnwal (2021). Carbon based nanodots in early diagnosis of cancer. Front Chem 9 669169. Impact Factor in 2021: 4.5

5. Mandeep Kaur, Akanksha Sharma, Santosh Kumar, Gurpal Singh and Ravi P. Barnwal (2021) SARS-CoV-2: Insights into its structural intricacies and functional aspects for drug and vaccine development. Int J Biol Macromol. 179, 45–60. Impact factor in 2020: 5.16

6. Neeraj Choudhary, Mary Chatterjee, Santosh Kumar, Gurpal Singh and Ashish Suttee. (2021) Effect of conventional method and Microwave Assisted Extraction on Phytoconstituents of Chenopodium album. Materials Today: Proceedings 45, 5362-5367. Impact Factor in 2021: 1.5

7. Mengxiao Ma, Santosh Kumar, Latha Purushothaman, Markus Babst, Christian Ungermann, Richard J. Chi, and Christopher G. Burd. (2018) Lipid trafficking by yeast Snx4 family SNX-BAR proteins promotes autophagy and vacuole membrane fusion. Mol Biol Cell, 29, 2190-2200. Impact Factor in 2018: 3.50

8. 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

9. Himanshu Malhotra, Navdeep Sheokand, Santosh Kumar, Anoop S. Chauhan, Manoj Kumar, Priyanka Jakhar, Vishant M. Boradia, Chaaya I. Raje and Manoj Raje. (2016) Exosomes: tunable nano vehicles for macromolecular delivery of transferrin and lactoferrin to specific intracellular compartment. J Biomed Nanotechnol, 12,1101-1114. Impact Factor in 2016: 5.00

10. Zahid Gani, Vishant M Boradia, Janaki Raghu Ram, Prashant M Suryavanshi, Pravinkumar Patil, Santosh Kumar , Ranvir Singh, Manoj Raje, and Chaaya I. Raje. (2016) Purification and characterization of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) from pea seeds. Protein Expr Purif, 127, 22-27. Impact Factor in 2016: 1.50

11. 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
Highlighted in “Spotlight” “How To Cock the Trigger (If you Are a Ciliate)” in The Euk. Cell. Impact Factor in 2015: 3.00

12. 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

13. Navdeep Sheokand, Himanshu Malhotra, Santosh Kumar, Vikas Tillu, Anoop Singh Chauhan, Chaaya Iyengar Raje, and Manoj Raje. (2014) Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells. J. Cell Sci. 127, 4279-4291. Impact factor in 2014: 5.40

14. 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
Highlighted in Nature Reviews Molecular Cell Biology 14, 751 (2013) “A sortilin for secretory granules”. Impact factor in 2013: 36.00 Highlighted in “In Focus” “Sortilins get a new delivery route” in The Journal of Cell Biology. Impact factor in 2013: 9.70 Accepted for cover image in The journal of Cell Biology. Impact factor in 2013: 9.70

15. 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

16. Navdeep Sheokand, Himanshu Malhotra, Santosh Kumar Vikas Tillu, and Manoj Raje. (2012) Cell surface GAPDH recruits Apo Tf to facilitate iron export in iron overloaded cells. AMER SOC CELL BIOLOGY, Conference paper

17. 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

18. Pooja Rawat, Santosh Kumar, Navdeep Sheokand, Chaaya Iyengar Raje and Manoj Raje. (2012) The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor. Biochem Cell Biol. 90, 329-338. Impact factor in 2012: 2.20

19. Chaaya Iyengar Raje, Santosh Kumar, Arti Harle, Jagpreet Singh Nanda and Manoj Raje. (2007) The macrophage cell surface Glyceraldehyde-3-phosphate dehydrogenase is a novel Transferrin receptor. J Biol Chem. 282, 3252–3261. Impact factor in 2007: 6.00

 

Patents

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

 

  1. Nikhat Firdaus Q. Khan, Technical Officer B
  2. Sakshi Gangurde, Project Assistant
  3. Amartya Pal, Junior Research Fellow
  4. Anisha Atre, Project trainee (July-December 2022)

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