MSB Lab.
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Lab members: Sajjan Rajpoot (Ph.D. Student), Kundan Solanki (Ph.D. Student), Khandu Digambar (Ph.D. Student), Pramod Patidar (Ph.D. Student), Lateef Rehman (Lab-Incharge), Mirza S Baig (PI)
Research Interest: Inflammation and Cancer
Inflammation and cancer- Our research focuses on the understanding of cell signaling pathways and transcriptional mechanisms that regulate the activation of macrophages in inflammation and cancer. Macrophage activation by microbial pattern recognition receptors, such as Toll-like receptors (TLRs), is critical for innate and adaptive immunity and has been extensively studied. However, these cells also play essential roles in resolving inflammation, maintaining tissue homeostasis and immune tolerance. We understand relatively little about the signaling pathways and molecular mechanisms that control the functions of macrophages in the context of their role in various chronic inflammatory conditions, including some cancers, rheumatoid arthritis, atherosclerosis, etc.
Targeted Drug Strategies for Cancer and Inflammation- We utilize virtual or computer-aided drug design methods to model new compounds complementary to a target protein’s shape and charge against inflammation and cancer. These virtually designed lead-like compounds could later be synthesized for biochemical and cellular testing. Drug repositioning can provide a safer alternative to developing new compounds as the repurposed drugs are clinically approved, have proven bio-availabilities, and well-characterized side-effect profiles.
Past trainees:
Dr. Kannan Muthu, Dr. Adnan Naim, Dr. Mansi Srivastava, Dr. Anjali Roy, Dr. Manikandan A., Siva Dallavalasa, Ajaykumar Kawale, Arshiya Khan, Sannan Mohammad, Ghazali Ahmad
Publications
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1. Wang Y, Li P, Solanki K, Li Y, Ma Z, Peppelenbosch MP, Baig MS, Pan Q. Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses. Virology. 2021 Oct 2;564:33-38. doi: 10.1016/j.virol.2021.09.009. [Epub ahead of print] PubMed PMID: 34619630; PubMed Central PMCID: PMC8486977
2. Rajpoot S, Ohishi T, Kumar A, Pan Q, Banerjee S, Zhang KYJ, Baig MS. A Novel Therapeutic Peptide Blocks SARS-CoV-2 Spike Protein Binding with Host Cell ACE2 Receptor. Drugs R D. 2021 Sep;21(3):273-283. doi: 10.1007/s40268-021-00357-0. Epub 2021 Jul 29. PubMed PMID: 34324175; PubMed Central PMCID: PMC8319882
3. Rajpoot S, Wary KK, Ibbott R, Liu D, Saqib U, Thurston TLM, Baig MS. TIRAP in the Mechanism of Inflammation. Front Immunol. 2021;12:697588. doi: 10.3389/fimmu.2021.697588. eCollection 2021. Review. PubMed PMID: 34305934; PubMed Central PMCID: PMC8297548
4.Vakhtangadze T, Singh Tak R, Singh U, Baig MS, Bezsonov E. Gender Differences in Atherosclerotic Vascular Disease: From Lipids to Clinical Outcomes. Front Cardiovasc Med. 2021;8:707889. doi: 10.3389/fcvm.2021.707889. eCollection 2021. Review. PubMed PMID: 34262956; PubMed Central PMCID: PMC8273377
5.Dabravolski SA, Bezsonov EE, Baig MS, Popkova TV, Orekhov AN. Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases. Int J Mol Sci. 2021 Jun 28;22(13). doi: 10.3390/ijms22136949. Review. PubMed PMID: 34203309; PubMed Central PMCID: PMC8268967
6.Dabravolski SA, Orekhova VA, Baig MS, Bezsonov EE, Starodubova AV, Popkova TV, Orekhov AN. The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes. Int J Mol Sci. 2021 Jun 23;22(13). doi: 10.3390/ijms22136733. Review. PubMed PMID: 34201756; PubMed Central PMCID: PMC8268113
7. Mezentsev A, Bezsonov E, Kashirskikh D, Baig MS, Eid AH, Orekhov A. Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside. Biomedicines. 2021 May 25;9(6). doi: 10.3390/biomedicines9060600. Review. PubMed PMID: 34070542; PubMed Central PMCID: PMC8228531.
8.Dabravolski SA, Bezsonov EE, Baig MS, Popkova TV, Nedosugova LV, Starodubova AV, Orekhov AN. Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk. Int J Mol Sci. 2021 Apr 24;22(9). doi: 10.3390/ijms22094459. Review. PubMed PMID: 33923295; PubMed Central PMCID: PMC8123173.
9. Saqib U. Masood A. Khan, Manikandan Alagumuthu , Suraj P. Parihar, Baig MS. Natural compounds as antiatherogenic agents. Cellular and Molecular Biology. 2021 January.
10. Rajpoot S, Alagumuthu M, Baig MS. Dual targeting of 3CLpro and PLpro of SARS-CoV-2: A novel structure-based design approach to treat COVID-19. Curr Res Struct Biol. 2021;3:9-18. doi: 10.1016/j.crstbi.2020.12.001. Epub 2020 Dec 10. PubMed PMID: 33319212; PubMed Central PMCID: PMC7726703.
11. Alagumuthu M, Rajpoot S, Baig MS. Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein. Cell Mol Bioeng. 2020 Oct 13;:1-9. doi: 10.1007/s12195-020-00658-5. [Epub ahead of print] PubMed PMID: 33072222; PubMed Central PMCID: PMC755336
12. Baig MS, Alagumuthu M, Rajpoot S, Saqib U. Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells. Drugs R D. 2020 Sep;20(3):161-169. doi: 10.1007/s40268-020-00312-5. PubMed PMID: 32592145; PubMed Central PMCID: PMC7319219.
13. Ohishi T, Abe H, Sakashita C, Saqib U, Baig MS, Ohba SI, Inoue H, Watanabe T, Shibasaki M, Kawada M. Inhibition of mitochondria ATP synthase suppresses prostate cancer growth through reduced insulin-like growth factor-1 secretion by prostate stromal cells. Int J Cancer. 2020 Jun 15;146(12):3474-3484. doi: 10.1002/ijc.32959. Epub 2020 Mar 19. PubMed PMID: 32144767.
14. Roy A, Saqib U, Wary K, Baig MS. Macrophage neuronal nitric oxide synthase (NOS1) controls the inflammatory response and foam cell formation in atherosclerosis. Int Immunopharmacol. 2020 Jun;83:106382. doi: 10.1016/j.intimp.2020.106382. Epub 2020 Mar 16. PubMed PMID: 32193098.
15. Baig MS, Roy A, Rajpoot S, Liu D, Savai R, Banerjee S, Kawada M, Faisal SM, Saluja R, Saqib U, Ohishi T, Wary KK. Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm Res. 2020 May;69(5):435-451. doi: 10.1007/s00011-020-01318-0. Epub 2020 Mar 11. Review. PubMed PMID: 32162012.
16. Naim A, Baig MS. Matrix metalloproteinase-8 (MMP-8) regulates the activation of hepatic stellate cells (HSCs) through the ERK-mediated pathway. Mol Cell Biochem. 2020 Apr;467(1-2):107-116. doi: 10.1007/s11010-020-03705-x. Epub 2020 Feb 27. PubMed PMID: 32108279.
17. Srivastava M, Saqib U, Banerjee S, Wary K, Kizil B, Muthu K, Baig MS. Inhibition of the TIRAP-c-Jun interaction as a therapeutic strategy for AP1-mediated inflammatory responses. Int Immunopharmacol. 2019 Jun;71:188-197. doi: 10.1016/j.intimp.2019.03.031. Epub 2019 Mar 22. PubMed PMID: 30909134.
18. Saqib U, Baig MS. Scaffolding role of TcpB in disrupting TLR4-Mal interactions: Three to tango. J Cell Biochem. 2019 Mar;120(3):3455-3458. doi: 10.1002/jcb.27619. Epub 2018 Sep 22. PubMed PMID: 30242887.
19. Roy A, Banerjee S, Saqib U, Baig MS. NOS1-derived nitric oxide facilitates macrophage uptake of low-density lipoprotein. J Cell Biochem. 2019 Feb 25;. doi: 10.1002/jcb.28439. [Epub ahead of print] PubMed PMID: 30805961.
20. Saqib U, Faisal SM, Saluja R, Baig MS. Structural insights of resveratrol with its binding partners in the toll-like receptor 4 pathway. J Cell Biochem. 2019 Jan;120(1):452-460. doi: 10.1002/jcb.27401. Epub 2018 Sep 6. PubMed PMID: 30191609.
21. Saqib U, Savai R, Liu D, Banerjee S, Baig MS. Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition. J Cell Biochem. 2018 Oct 29;. doi: 10.1002/jcb.27334. [Epub ahead of print] PubMed PMID: 30370939.
22. Saqib U, Kelley TT, Panguluri SK, Liu D, Savai R, Baig MS, Schürer SC. Polypharmacology or Promiscuity? Structural Interactions of Resveratrol With Its Bandwagon of Targets. Front Pharmacol. 2018;9:1201. doi: 10.3389/fphar.2018.01201. eCollection 2018. Review. PubMed PMID: 30405416; PubMed Central PMCID: PMC6207623.
23. Huang Y, Chen Z, Jang JH, Baig MS, Bertolet G, Schroeder C, Huang S, Hu Q, Zhao Y, Lewis DE, Qin L, Zhu MX, Liu D. PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse. J Allergy Clin Immunol. 2018 Oct;142(4):1311-1321.e8. doi: 10.1016/j.jaci.2018.02.050. Epub 2018 Apr 18. PubMed PMID: 29679656; PubMed Central PMCID: PMC6324560.
​24. Baig MS, Roy A, Saqib U, Rajpoot S, Srivastava M, Naim A, Liu D, Saluja R, Faisal SM, Pan Q, Turkowski K, Darwhekar GN, Savai R. Repurposing Thioridazine (TDZ) as an anti-inflammatory agent. Sci Rep. 2018 Aug 20;8(1):12471. doi: 10.1038/s41598-018-30763-5. PubMed PMID: 30127400; PubMed Central PMCID: PMC6102213.
25. Thangam EB, Jemima EA, Singh H, Baig MS, Khan M, Mathias CB, Church MK, Saluja R. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front Immunol. 2018;9:1873. doi: 10.3389/fimmu.2018.01873. eCollection 2018. Review. PubMed PMID: 30150993; PubMed Central PMCID: PMC6099187.
26. Srivastava M, Baig MS. NOS1 mediates AP1 nuclear translocation and inflammatory response. Biomed Pharmacother. 2018 Jun;102:839-847. doi: 10.1016/j.biopha.2018.03.069. Epub 2018 Apr 5. PubMed PMID: 29605772.
27. Saqib U, Sarkar S, Suk K, Mohammad O, Baig MS, Savai R. Phytochemicals as modulators of M1-M2 macrophages in inflammation. Oncotarget. 2018 Apr 3;9(25):17937-17950. doi: 10.18632/oncotarget.24788. eCollection 2018 Apr 3. Review. PubMed PMID: 29707159; PubMed Central PMCID: PMC5915167.
28. Saqib U, Baig MS. Identifying the inhibition of TIR proteins involved in TLR signalling as an anti-inflammatory strategy. SAR QSAR Environ Res. 2018 Apr;29(4):295-318. doi: 10.1080/1062936X.2018.1431308. Epub 2018 Feb 15. PubMed PMID: 29448819.
29. Naim A, Pan Q, Baig MS. Matrix Metalloproteinases (MMPs) in Liver Diseases. J Clin Exp Hepatol. 2017 Dec;7(4):367-372. doi: 10.1016/j.jceh.2017.09.004. Epub 2017 Oct 3. Review. PubMed PMID: 29234202; PubMed Central PMCID: PMC5715451.
30. Baig MS, Liu D, Muthu K, Roy A, Saqib U, Naim A, Faisal SM, Srivastava M, Saluja R. Heterotrimeric complex of p38 MAPK, PKCδ, and TIRAP is required for AP1 mediated inflammatory response. Int Immunopharmacol. 2017 Jul;48:211-218. doi: 10.1016/j.intimp.2017.04.028. Epub 2017 May 18. PubMed PMID: 28528205.
31. Saqib U, Sarkar S, Baig MS. Inflammation and its Disease Consequences. Journal of Immune Research. 2017 April; 4(1):1027.
32. Srivastava M, Saqib U, Naim A, Roy A, Liu D, Bhatnagar D, Ravinder R, Baig MS. The TLR4-NOS1-AP1 signaling axis regulates macrophage polarization. Inflamm Res. 2017 Apr;66(4):323-334. doi: 10.1007/s00011-016-1017-z. Epub 2016 Dec 24. PubMed PMID: 28013342.
33. Faisal SM, Varma VP, Subathra M, Azam S, Sunkara AK, Akif M, Baig MS, Chang YF. Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated inflammatory responses in macrophages. Sci Rep. 2016 Dec 20;6:39530. doi: 10.1038/srep39530. PubMed PMID: 27996041; PubMed Central PMCID: PMC5172228.
34. Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, Bishnoi S, Baig MS. Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol. 2016 Nov;40:79-89. doi: 10.1016/j.intimp.2016.08.026. Epub 2016 Aug 30. Review. PubMed PMID: 27584057.
35. Saqib U, Baig MS. Inhibitors of Toll-Like Receptor 4 (TLR4) – Homodimerization: Nipping in the Bud. Int. J. Drug Dev. & Res.. 2016 August; 8:20-23.
36. Baig MS, Yaqoob U, Cao S, Saqib U, Shah VH. Non-canonical role of matrix metalloprotease (MMP) in activation and migration of hepatic stellate cells (HSCs). Life Sci. 2016 Jun 15;155:155-60. doi: 10.1016/j.lfs.2016.04.031. Epub 2016 Apr 29. PubMed PMID: 27140333.
37. Uzma S, Baig MS. Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases. Drug Des Devel Ther. 2016;10:1557-72. doi: 10.2147/DDDT.S103393. eCollection 2016. PubMed PMID: 27217723; PubMed Central PMCID: PMC4862341.
38. Baig MS, Zaichick SV, Mao M, de Abreu AL, Bakhshi FR, Hart PC, Saqib U, Deng J, Chatterjee S, Block ML, Vogel SM, Malik AB, Consolaro ME, Christman JW, Minshall RD, Gantner BN, Bonini MG. NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1. J Exp Med. 2015 Sep 21;212(10):1725-38. doi: 10.1084/jem.20140654. Epub 2015 Aug 31. PubMed PMID: 26324446; PubMed Central PMCID: PMC4577833
39. Saqib U, Baig MS. Probing PARP1-inhibitor complexes for the development of novel inhibitors. Cell Mol Biol (Noisy-le-grand). 2014 Oct 25;60(3):43-52. PubMed PMID: 25346248.
40. Gangwar S, Baig MS, Shah P, Biswas S, Batra S, Siddiqi MI, Goyal N. Identification of novel inhibitors of dipeptidylcarboxypeptidase of Leishmania donovani via ligand-based virtual screening and biological evaluation. Chem Biol Drug Des. 2012 Feb;79(2):149-56. doi: 10.1111/j.1747-0285.2011.01262.x. Epub 2011 Nov 28. PubMed PMID: 22014034.
41. Baig MS, Gangwar S, Goyal N. Biochemical characterization of dipeptidylcarboxypeptidase of Leishmania donovani. Cell Mol Biol (Noisy-le-grand). 2011 Feb 12;57(1):56-61. PubMed PMID: 21366963.
42. Baig MS, Kumar A, Siddiqi MI, Goyal N. Characterization of dipeptidylcarboxypeptidase of Leishmania donovani: a molecular model for structure based design of antileishmanials. J Comput Aided Mol Des. 2010 Jan;24(1):77-87. doi: 10.1007/s10822-009-9315-y. Epub 2009 Dec 29. PubMed PMID: 20039100.
43. Baig MS, Manickam N. Homology modeling and docking studies of Comamonas testosteroni B-356 biphenyl-2,3-dioxygenase involved in degradation of polychlorinated biphenyls. Int J Biol Macromol. 2010 Jan 1;46(1):47-53. doi: 10.1016/j.ijbiomac.2009.10.014. Epub 2009 Oct 30. PubMed PMID: 19879892.
44. Goyal N, Duncan R, Selvapandiyan A, Debrabant A, Baig MS, Nakhasi HL. Cloning and characterization of angiotensin converting enzyme related dipeptidylcarboxypeptidase from Leishmania donovani. Mol Biochem Parasitol. 2006 Feb;145(2):147-57. doi: 10.1016/j.molbiopara.2005.09.014. Epub 2005 Oct 12. PubMed PMID: 16257064.
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45. Roy A, Saqib U, Baig MS. NOS1-mediated macrophage and endothelial cell interaction in the progression of atherosclerosis. Cell Biol Int. 2021 Jun;45(6):1191-1201. doi: 10.1002/cbin.11558. Epub 2021 Feb 4. PubMed PMID: 33501735.
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