Publications

Selected Publications

This study investigated metabolic requirements of NETosis using both ROS -dependent and independent mechanism. Glycolysis dependent lactate formation was found as a common mechanism for NETs formation


Awasthi D, Nagarkoti S, Sadaf S, Chandra T, Kumar S, Dikshit M. Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis. Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165542

https://www.sciencedirect.com/science/article/pii/S0925443919302650?via%3Dihub#f0005

Kumar S, Dikshit M. Metabolic Insight of Neutrophils in Health and Disease. Front Immunol. 2019 Sep 20;10:2099.

https://www.frontiersin.org/articles/10.3389/fimmu.2019.02099/full

This work discusses recent developments in understanding of the metabolic regulation, that may provide clues for better management and newer therapeutic opportunities for neutrophil centric immuno-deficiencies and inflammatory disorders.

Kumar S, Nattamai KJ, Hassan A, Amoah A, Karns R, Zhang C, Liang Y, Shimamura A, Florian MC, Bissels U, Luevano M, Bosio A, Davies SM, Mulaw M, Geiger H, Myers KC. Repolarization of HSC attenuates HSCs failure in Shwachman-Diamond syndrome. Leukemia. 2020 Oct 19. doi: 10.1038/s41375-020-01054-8. https://www.nature.com/articles/s41375-020-01054-8

Shwachman-Diamond syndrome (SDS), a bone marrow failure (BMF) syndrome found to present with a reduced activity of the small Rho GTPase Cdc42 and concomitantly a reduced frequency of HSCs polar for polarity proteins in primitive hematopoietic cells. The level of apolarity of SDS HSCs correlated with the magnitude of HSC depletion in SDS patients. Importantly, exogenous elevation of the activity of Cdc42 restored polarity in SDS HSCs and increased the number of HSCs in SDS patient samples in surrogate assays.

Kumar S#, Geiger H#. HSC Niche Biology and HSC Expansion Ex Vivo. Trends Mol Med. 2017 Sep;23(9):799-819

https://www.sciencedirect.com/science/article/pii/S1471491417301107?via%3Dihub

Hematopoietic stem cell (HSC) transplantation can restore a new functional hematopoietic system, thus expansion of HSCs and HSC self-renewal ex vivo is highly desired to greatly improve transplantation therapy in the clinic. Here we discuss current knowledge of niche biology, the intrinsic regulators of HSC self-renewal in vivo, and introduce novel niche-informed strategies of HSC expansion ex vivo.

Kumar S, Xu J, Perkins C, Guo F, Snapper S, Finkelman FD, Zheng Y, and Filippi MD. Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules. Blood. 2012, 120: 3563-74.

https://ashpublications.org/blood/article/120/17/3563/30632/Cdc42-regulates-neutrophil-migration-via-crosstalk

This study investigated neutrophil infiltration in acute lung injury model. Data obtained revealed Cdc42 mediated polarity regulation in neutrophil chemotaxis through integrin dependent mechanism. Targeting neutrophil recruitment to inflamed tissue is also a promising approach to mitigate tissue inflammation and injury.

Kumar S, Xu J, Kumar RS, Kofron M, Chrzanowska-Wodnicka M, Filippi MD. The Small GTPase Rap1b negatively regulates neutrophil chemotaxis and trans-cellular diapedesis by inhibiting Akt activation. J Exp Med, 2014 Aug 25;211(9):1741-58.

https://rupress.org/jem/article/211/9/1741/41807/The-small-GTPase-Rap1b-negatively-regulates

This study identified trans-cellular diapedesis as damaging mechanism during acute lung injury. Rap1b deficiency promoted the transcellular route of diapedesis through endothelial cell with enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. These neutrophils were also observed to have more invadopodia-like protrusions and matrix degradation ability.

Patel S*, Kumar S*, Jyoti A, Srinag S, Keshari RS, Saluja R, Verma A, Mitra K. Barthwal MK, Krishnamurthy H, Bajpai VK, and Dikshit M. Nitric oxide donors release extracellular traps from human neutrophils by augmenting free radical generation. NO Biology 2010; 22(3):226-34.

https://www.sciencedirect.com/science/article/pii/S1089860310000030



This study first time reported nitric oxide (NO) mediated free radical generation and NETs formation from human neutrophils.

Peer-reviewed Publications


35. Singhal A, Yadav S, Chandra T, Mulay SR, Gaikwad AN, Kumar S. An imaging and computational algorithm for efficient identification and quantification of neutrophil extracellular traps. Cells 2022, 11(2), 191; https://doi.org/10.3390/cells11020191


34. Singhal A, Kumar S. Neutrophil and remnant clearance in immunity and inflammation. Immunology. 2021 Oct 26. doi: 10.1111/imm.13423.


33. Singhal A, Dhankani P, Gupta KL, Mazumder J, R A, Dikshit M, Kumar S. Rho signaling inhibition mitigates lung injury via targeting neutrophil recruitment and selectin-AKT signaling. Biochim Biophys Acta Mol Cell Res. 2021 Nov;1868(12):119122.


32. Serrano-Lopez J, Hegde S, Kumar S, Serrano J, Fang J, Wellendorf AM, Roche PA, Rangel Y, Carrington LJ, Geiger H, Grime HL, Luther S, Maillard I, Sanchez-Garcia J, Starczynowski DT, Cancelas JA. Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics. Elife 2021 Apr 8;10:e66190

31. Sadaf S, Nagarkoti S, Awasthi D, Singh AK, Srivastava RN, Kumar S, Barthwal MK, Dikshit M. nNOS induction and NOSIP interaction impact granulopoiesis and neutrophil differentiation by modulating nitric oxide generation. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 2021 Jun;1868(7):119018.


30. Kumar S, Nattamai KJ, Hassan A, Amoah A, Karns R, Zhang C, Liang Y, Shimamura A, Florian MC, Bissels U, Luevano M, Bosio A, Davies SM, Mulaw M, Geiger H, Myers KC. Repolarization of HSC attenuates HSCs failure in Shwachman-Diamond syndrome. Leukemia. 2020 Oct 19. doi: 10.1038/s41375-020-01054-8.

29. Gupta P, Kumar A, Pal S, Kumar S, Lahiri A, Kumaravelu J, Chattopadhyay N, Dikshit M, Barthwal MK. Standardized Xylocarpus moluccensis fruit fraction mitigates collagen-induced arthritis in mice by regulating immune response. J Pharm Pharmacol. 2020 Apr;72(4):619-632.

28. Sadaf S, Awasthi D, Singh AK, Nagarkoti S, Kumar S, Barthwal MK, Dikshit M. Pyroptotic and apoptotic cell death in iNOS and nNOS overexpressing K562 cells: A mechanistic insight. Biochem Pharmacol. 2020 Jun;176:113779. doi: 10.1016/j.bcp.2019.113779.

27. Kumar S, Dikshit M. Metabolic Insight of Neutrophils in Health and Disease. Front Immunol. 2019 Sep 20;10:2099.

26. Awasthi D, Nagarkoti S, Sadaf S, Chandra T, Kumar S, Dikshit M. Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis. Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165542.

25. Nagarkoti S, Dubey M, Sadaf S, Awasthi D, Chandra T, Jagavelu K, Kumar S, Dikshit M. Catalase S-Glutathionylation by NOX2 and Mitochondrial-Derived ROS Adversely Affects Mice and Human Neutrophil Survival. Inflammation. 2019 Oct 23. doi: 10.1007/s10753-019-01093-z.

24. Sadaf S, Singh AK, Awasthi D, Nagarkoti S, Agrahari AK, Srivastava RN, Jagavelu K, Kumar S, Barthwal MK, Dikshit M. Augmentation of iNOS expression in myeloid progenitor cells expedites neutrophil differentiation. J Leukoc Biol. 2019 Mar 12. doi: 10.1002/JLB.1A0918-349RR. [Epub ahead of print]

23. Nagarkoti S, Sadaf S, Awasthi D, Chandra T, Jagavelu K, Kumar S, Dikshit M. L-Arginine and tetrahydrobiopterin supported nitric oxide production is crucial for the microbicidal activity of neutrophils. Free Radic Res. 2019 Feb 4:1-12.

22. Misra A, Prakash P, Aggarwal H, Dhankani P, Kumar S, Pandey CP, Pugh N, Bihan D, Barthwal MK, Farndale RW, Dikshit DK, Dikshit M. Anti-thrombotic efficacy of S007-867: Pre-clinical evaluation in experimental models of thrombosis in vivo and in vitro. Biochem Pharmacol. 2018 Feb;148:288-297.

21. Nagarkoti S, Dubey M, Awasthi D, Kumar V, Chandra T, Kumar S, Dikshit M. S-Glutathionylation of p47phox sustains superoxide generation in activated neutrophils. Biochim Biophys Acta. 2018 Feb;1865(2):444-454.

20. Kumar S#, Geiger H#. HSC Niche Biology and HSC Expansion Ex Vivo. Trends Mol Med. 2017 Sep;23(9):799-819 (Co-corresponding)

19. Hinge A, Xu J, Javier J, Mose E, Kumar S, Kapur R, Srour EF, Malik P, Aronow BJ, Filippi MD. p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. Nat Commun. 2017 Feb 8;8:14382. doi: 10.1038/ncomms14382.

18. Kanshana JS, Khanna V, Singh V, Jain M, Misra A, Kumar S, Farooqui M, Barthwal MK, Dikshit M Progression and characterization of the accelerated atherosclerosis in iliac artery of New Zealand White rabbits: effect of Simvastatin. J Cardiovasc Pharmacol. 2017 May;69(5):314-325.

17. Kumar S#, Filippi MD#. An alternative approach for sample preparation to perform transmission electron microscopy (TEM) analysis on rare cells. J of Visualized Experiments. 2016 in press (Co-corresponding)

16. Dubey M, Singh AK, Awasthi D, Nagarkoti S, Kumar S, Ali W, Chandra T, Kumar V, Barthwal MK, Jagavelu K, Sánchez-Gómez FJ, Lamas S, Dikshit M. L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions. Free Radic Biol Med. 2015 Apr 14;86:1-15.

15. Kumar S, Xu J, Kumar RS, Kofron M, Chrzanowska-Wodnicka M, Filippi MD. The Small GTPase Rap1b negatively regulates neutrophil chemotaxis and trans-cellular diapedesis by inhibiting Akt activation. J Exp Med, 2014 Aug 25;211(9):1741-58.

14. Kumar S#, Ciraolo G, Hinge A, Filippi MD#. An efficient and reproducible process for transmission electron microscopy (TEM) of rare cell populations. J of Immunological methods. 2014 Feb;404:87-90. (# Co-corresponding)

13. Boespflug ND, Kumar S, McAlees JW, Phelan JW, Grimes HL, Hoebe K, Hai T, Filippi MD, Karp CL. ­ATF3 is a novel regulator of mouse neutrophil migration. Blood Mar 27;123(13):2084-93. Highlighted on Blood cover with preview commentary.

12. Jyoti A, Singh AK, Dubey M, Kumar S, Saluja R, Keshari RS, Verma A, Chandra T, Kumar A, Bajpai VK, Barthwal MK, Dikshit M. Interaction of Inducible Nitric Oxide Synthase with Rac2 Regulates Reactive Oxygen and Nitrogen Species Generation in the Human Neutrophil Phagosomes: Implication in Microbial Killing. Antioxid Redox Signal. 2014 Jan 20; 20(3):417-31. Highlighted on ARS J cover.

11. Kumar S, Xu J, Perkins C, Guo F, Snapper S, Finkelman FD, Zheng Y, and Filippi MD. Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules. Blood. 2012, 120: 3563-74.

10. Raman R, Kumar RS, Hinge A, Kumar S, Nayak RC, Xu J, Szczur K, Cancelas JA, Filippi MD. p190-B RhoGAP regulates the functional composition of the mesenchymal microenvironment. Leukemia 2013 Nov;27(11):2209-19.

9. Bosco EE, Kumar S, Marchioni F, Biesiada J, Kordos M, Szczur K, Meller J, Seibel W, Mizrahi A, Pick E, Filippi MD, Zheng Y. Rational Design of Small Molecule Inhibitors Targeting the Rac GTPase-p67(phox) Signaling Axis in Inflammation. Chem Biol. 2012; 19(2): 228-42. Highlighted as preview commentary in Chem Biol Journal.

8. Kumar S, Barthwal MK and Dikshit M. CDK2 nitrosylation and loss of mitochondrial potential mediates NO dependent biphasic regulation of HL-60 cell cycle. Free Radical Biology and Medicine, 2010; 48(6):851-61.

7. Kumar S, Jyoti A, Keshari RS, Singh M, Barthwal MK and Dikshit M. Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells. Cytometry A. 2010; 77(5):467-77.

6. Kumar S, Barthwal MK and Dikshit M. Nitrite mediated modulation of HL-60 cell cycle and proliferation: role of Cdk2 activation. J Pharmacol Exp Ther. 2011;337(3):812-21.

5. Kumar S, Patel S, Jyoti A, Keshari RS, Verma A, Barthwal MK, Dikshit M. Nitric oxide-mediated augmentation of neutrophil reactive oxygen and nitrogen species formation: Critical use of probes. Cytometry A. 2010; 77(11):1038-48. Highlighted as preview commentary in Cytometry A.

4. Patel S*, Kumar S*, Jyoti A, Srinag S, Keshari RS, Saluja R, Verma A, Mitra K. Barthwal MK, Krishnamurthy H, Bajpai VK, and Dikshit M. Nitric oxide donors release extracellular traps from human neutrophils by augmenting free radical generation. NO Biology 2010; 22(3):226-34. (*Equal contributor)

3. Keshari RS, Jyoti A, Kumar S, Dubey M, Verma A, Srinag BS, Krishnamurthy H, Barthwal MK, Dikshit M. Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential. Cytometry A. 2012 Mar;81(3):238-47

2. Singh S, Kumar S, and Madhu Dikshit. Involvement of mitochondrial apoptotic pathway in dopaminergic neuronal death in Parkinson’s disease rat models. Redox Rep. 2010; 15(3):115-22.

1. Sankaranarayanan A, Narender T, Kumar S, and Dikshit M. Allium sativum constituents: Effect on free radical generation from rat neutrophils. Cell Mol Biol. 2007; 53: 63-67.

BOOK CHAPTERS:


  1. Kumar S, Dikshit M. Neutrophil phagocytosis assay. Flow cytometry lab protocols: Protocols from the international cytometry workshops. 49-51; 2010

  2. Kumar S, Dikshit M. Respiratory burst / free radical assay. Flow cytometry lab protocols: Protocols from the international cytometry workshops. 53-56; 2010

  3. Kumar S, Filippi MD. Molecular Regulation of Granulopoiesis. The Neutrophils New Outlook for Old Cells 3rd Edition 1-41; 2013

  4. Kumar S, Dikshit M. Reactive Oxygen Species Generation in Neutrophils: Modulation by Nitric Oxide- Modulation of Oxidative Stress in Heart Disease, 2019 pp 197-214