Dr. Syed Sajad Hussain

Cancer Pharmacology Division
CSIR - Indian Institute of Integrative Medicine,Canal Road, Jammu – 180001
Email: sshussain@iiim.ac.in

Positions Held  
Position Held Date Organization
Senior Scientist  2015 - Present CSIR-IIIM

Research Area

Chromatin is a repeated structure of small bead like structures called Nucleosomes core particles (NCP), connected by a small piece of DNA called linker DNA. The NCP in turn, is composed of two copies each, of four basic histone, namely H2A, H2B, H3 and H4. These basic histones are well conserved protein with a central well structured protein domain called “histone fold” and unstructured N- and C terminal tails. The histone folds of individual histones interact with each other through hand shake motif interactions to form the octamer. This octamer interacts directly with the DNA (minor grooves) wrapped around it to complete the NCP.  The tails are floating out of the NCP and are main targets for the post translation modification which have role in chromatin dynamics and function. There are, however, some modifications also reported for the aminoacid residues present in the histone fold domain (e.g. H3k79) which have roles in different cellular processes.
Our lab is interested to study the role of small molecules, which can target epigenetic modifications relevant to cancer and Induced pluripotent stem cell generation.

Publications
  • Bednar, J.; Garcia-Saez, I.; Boopathi, R.; Cutter, A.R.; Papai ,G.; Reymer, A.; Syed, S.H.; Lone, I.N.; Tonchev, O.; Crucifix, C.; Menoni, H.; Papin, C.; Skoufias, D.A.; Kurumizaka, H.; Lavery, R.; Hamiche, A.; Hayes, J.J.; Schultz, P.; Angelov, D.; Petosa, C.; Dimitrov ,S. Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1. Mol Cell. (2017) ,66(3):384-397.e8.

  • Nalli ,Y.;  Gupta, G.;   Nadkarni ‘,R.J.;  Gupta, V.K.;   Syed, S.H.; and    Ali, A. Divergent synthesis of prenylated carbazole alkaloid (+)-S-mahanimbine led to the discovery of a notch activator. RSC Adv. (2016),6, 83069-83077

  • Dar, M.S.; Singh ,P.; Singh, G.; Jamwal, G.; Syed, S.H.; Rana, A.; Akhter ,Y.; Monga, S.P.; Dar, M.J. Terminal regions of β-catenin are critical for regulating its adhesion and transcription functions. Biochim Biophys Acta. (2016) ,1863(9):2345-57.

  • Roulland, Y.; Ouararhni, K.; Naidenov, M.; Ramos ,L.; Shuaib, M.; Syed ,S.H.; Lone, I.N.; Boopathi, R.; Fontaine, E.; Papai, G.; Tachiwana,H.; Gautier, T.; Skoufias, D.; Padmanabhan, K.; Bednar ,J.; Kurumizaka, H.; Schultz, P.; Angelov, D.; Hamiche, A.; Dimitrov, S. The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity.  Mol Cell. (2016) ,63(4):674-85.  

  • Sawant, S.D.; Lakshma, R. G.; Dar, M.I.; Srinivas, M.; Gupta, G.; Sahu ,P.K.; Mahajan, P.; Nargotra, A.; Singh,S.; Sharma ,S.C.; Tikoo ,M.; Singh, G.; Vishwakarma, R.A.; Syed, S.H. Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5. Bioorg Med Chem. (2015) ,23(9):2121-8. 

  • Meyer, S.; Becker, N.B.; Syed. S.H.; Goutte-Gattat ,D.; Shukla, M.S.; Hayes, J.J.; Angelov ,D.; Bednar, J.; Dimitrov, S.; Everaers, R. From crystal and NMR structures, footprints and cryo-electron-micrographs to large and soft structures: nanoscale modeling of the nucleosomal stem. Nucleic Acids Res. (2011) ,39(21):9139-54.

  • Gadad, S.S.; Senapati, P.; Syed, S.H.; Rajan, R.E.; Shandilya, J.; Swaminathan ,V.; Chatterjee, S.; Colombo, E.; Dimitrov, S.; Pelicci, P.G.; Ranga, U.; Kundu, T.K. The multifunctional protein nucleophosmin (NPM1) is a human linker histone H1 chaperone. Biochemistry. (2011) ,50(14):2780-9. 

  • Fazili, K.M.;  Ali ,Y.; Syed ,S.H.;  Andrabi ,A.; Wafia, B.A. Karyotype of apomictic Dandelion (Taraxacum officinale), a wild plant with high medicinal value. Recent Research in Science and Technology (2011), 3(10): 118-121

  • Shukla, M.S.; Syed, S.H.; Goutte-Gattat, D.; Richard, J.L.; Montel, F.; Hamiche, A.;Travers, A.; Faivre-Moskalenko, C.; Bednar ,J.; Hayes, J.J.; Angelov ,D.; Dimitrov, S.  The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling. Nucleic Acids Res. (2011) ,39(7):2559-70.

  • Syed, S.H.; Goutte-Gattat, D.; Becker, N.; Meyer, S.; Shukla, M.S.; Hayes, J.J.; Everaers, R.; Angelov, D.; Bednar, J.; Dimitrov ,S. Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome. Proc Natl Acad Sci U S A.(2010) ,107(21):9620-5. 

  • Shukla, M.S.; Syed, S.H.; Montel, F.; Faivre-Moskalenko, C.; Bednar, J.; Travers, A.; Angelov, D.; Dimitrov, S. Remosomes: RSC generated non-mobilized particles with approximately 180 bp DNA loosely associated with the histone octamer. Proc Natl Acad Sci U S A. (2010) ,107(5):1936-41.
  • Syed, S.H.; Boulard, M.; Shukla,M.S.; Gautier, T.; Travers, A.; Bednar, J.; Faivre-Moskalenko, C.; Dimitrov, S.; Angelov, D. The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome. Nucleic Acids Res. (2009) ,37(14):4684-95.   
  • Karmodiya, K.; Modak ,R.; Sahoo, N.; Sajad, S.; Surolia, N. Deciphering the key residues in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase responsible for interactions with Plasmodium falciparum acyl carrier protein. FEBS J. (2008), 275(19):4756-66. 
  • Karmodiya, K.; Sajad, S.; Sinha, S.; Maity ,K.; Suguna, K.; Surolia, N. Conformational stability and thermodynamic characterization of homotetrameric Plasmodium falciparum beta-ketoacyl-ACP reductase. IUBMB Life. (2007) ,59(7):441-9.

Patents:

  • Pyrazolopyrimidinones as PDE5 inhibitors and process for the preparation thereof
    Inventers: Sawant,S. D. ; Reddy, G.L. ;Srinivas,M. ; Hussain,Syed Sajad. ; Dar,Mohd Ishaq.; Nargotra, A. ;Mahajan,P. ; Vishwakarma,R. A.
    (NF No. : 0106NF2013 (May 2013))

Current Students

1
Mohd. Ishaq Dar
2
Gourav Gupta
3
Suraya Jan