Dr. Chinmay K. Mukhopadhyay, Professor
Prof. Mukhopadhyay received his Ph.D. from the Department of Biochemistry from Calcutta University. He received the postdoctoral training at the Department of Cell Biology, Cleveland Clinic Foundation, USA. He joined at the ‘Special Centre for Molecular Medicine’ in 2001. Prof. Mukhopadhyay received International Senior Research Fellowship from The Wellcome Trust, UK. He is an elected member of Guha Research Conference and Fellow of The National Academy of Sciences. He is an Editorial Board Member in the journal Scientific Reports and Reviewing Editor of Frontiers in Physiology.
Iron is essential micronutrient for all the organisms because of its ability to function as a protein bound red-ox element. Defective regulation of iron homeostasis leads to either, iron excess and related tissue injuries due to iron-stimulated oxidative damage or iron deficiency disorders. Alterations of iron pool are implicated in tissue injury, diabetes and obesity, cancers, neurodegenerative diseases, inflammation and infections. Prof. Mukhopadhyay’s research interest includes understanding the role of iron in insulin resistance and related disorders, neurodegenerative diseases like Parkinson’s disease. He is also interested in unravelling mechanisms by which protozoan parasite Leishmania donovani alters iron homeostasis in macrophages for its survival and growth, His recent research interest extends in understanding the role of iron and reactive oxygen species in inflammation of macrophages and microglia.
Mukhopadhyay CK. Understanding the role and regulation of ferroportin in reactive oxygen species-induced activation of microglia. Science and Engineering Research Board, 2021-2024
The project aims to explore the role of exogenous and endogenous reactive oxygen species in regulating iron exporter ferroportin and its role in activation of microglia.
Mukhopadhyay CK. Role of norepinephrine on mitochondrial iron homeostasis in astroglial cell. Department of Biotechnology. 2023-2026
The project aims to understand the role of norepinephrine on astroglial mitochondrial iron homeostasis, ATP generation and release. This may be helpful in regulating ATP release from astroglia to modulate postsynaptic efficacy affected in several neurodegenerative diseases.
Prof. Neena Singh, Case Western Reserve University, USA
Prof. Pankaj Seth, National Brain Research Centre, Manesar
Prof. Amit Dinda, All India Institute of Medical Sciences, New Delhi
- Sen S, Bal SK, Yadav S, Mishra P, Vivek VG, Rastogi R, Mukhopadhyay CK. Intracellular pathogen Leishmania intervenes in iron loading into ferritin by cleaving chaperones in host macrophages as an iron acquisition strategy. J. Biol. Chem. 298:102646, 2022
- Gupta P, Singh P, Pandey HS, Seth P, Mukhopadhyay CK. Phosphoinositide-3-kinase inhibition elevates ferritin level resulting depletion of labile iron pool and blocking of glioma cell proliferation. Biochim Biophys Acta - General Subjects, 1863(3):547-564, 2019
- Das NK, Sandhya S, Vishnu Vivek G, Kumar R, Singh AK, Bal SK, Kumari S, Mukhopadhyay CK.. Leishmania donovani inhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages. Cell Microbiol. 20(7):e12834. 2018
- Dev S, Kumari S, Singh N, Bal SK, Seth P, Mukhopadhyay CK. Role of extracellular hydrogen peroxide on regulation of iron homeostasis genes in neuronal cell: Implication in iron accumulation. Free Radical Biol Med. 86:78-89, 2015.
- Tapryal N, Vivek VG, Mukhopadhyay CK. Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein: Implication in energy homeostasis. J. Biol. Chem. 290:7634-7646, 2015
- Biswas S, Tapryal N, Mukherjee R, Kumar R, Mukhopadhyay CK. Insulin promotes iron uptake in human hepatic cell by regulating transferrin receptor-1 transcription mediated by hypoxia inducible factor-1. Biochim Biophys Acta. 1832(2):293-301, 2013
- Tapryal N, Mukhopadhyay C, Mishra MK, Das D, Biswas S, Mukhopadhyay CK. Glutathione synthesis inhibitor butathione sulfoximine regulates ceruloplasmin by dual but opposite mechanism: Implication in hepatic iron overload. Free Radic Biol Med. 48:1492-1500, 2010.
- Tapryal N, Mukhopadhyay ., Das D, Fox PL, Mukhopadhyay CK. Reactive oxygen species regulate ceruloplasmin by a novel mRNA decay mechanism involving its 3'-untranslated region: Implications in neurodegenerative diseases. J. Biol. Chem. 284:1873-1883, 2009.
- Das NK, Biswas S, Solanki S, Mukhopadhyay CK. Leishmania donovani depletes labile iron pool to exploit iron uptake capacity of macrophage for its intracellular growth. Cell Microbiol. 11:83-94, 2009.
- Biswas S, Gupta MK, Chattopadhyay D, Mukhopadhyay CK. Insulin induced activation of hypoxia inducible factor-1 requires generation of reactive oxygen species by NADPH oxidase. Am. J. Physiol. Heart and Circulatory Physiology 292:H758-766, 2007.
- Das D, Tapryal N, Goswami SK, Fox PL, Mukhopadhyay CK. Regulation of Ceruloplasmin in human hepatic cells by redox active copper: Identification of a novel AP-1 site in ceruloplasmin gene. Biochem J. 402:135-141, 2007.
- Seshadri V, Fox PL. Mukhopadhyay CK. Dual role of insulin in transcriptional regulation of the acute phase reactant ceruloplasmin. J Biol Chem. 277: 27903-27911, 2002.
- Mukhopadhyay CK, Attieh ZK. Fox PL. Role of ceruloplasmin in cellular iron uptake. Science. 279: 714-717, 1998.
- Mukhopadhyay CK, Mazumder B, Lindley PF, Fox PL. Identification of the prooxidant site of human ceruloplasmin: A model for oxidative damage by copper bound to protein surfaces. Proc. Natl. Acad. Sci. USA, 94:11546-11551, 1997.
- Mukhopadhyay CK, Chatterjee IB. Free metal ion-independent oxidative damage of collagen. Protection by ascorbic acid. J. Biol. Chem. 269:30200-30205, 1994.
- Mukhopadhyay CK, Chatterjee IB. NADPH-initiated cytochrome P450-mediated free metal ion-independent oxidative damage of microsomal proteins. Exclusive prevention by ascorbic acid. J. Biol. Chem. 269: 13390-13397, 1994.
Number of students awarded/submitted Ph. D.: 25
Number of Ph. D. students currently enrolled: 07
Dr. Rakesh K. Tyagi, Professor
Prof. Rakesh K. Tyagi carried out his doctoral studies at Jawaharlal Nehru University, New Delhi. Subsequently, he pursued his research work in the area of ‘Molecular Endocrinology’ as a Fienberg Fellow at the Weizmann Institute of Since, Israel, and later as INSERM international fellow in France. Prior to joining the ‘Special Centre for Molecular Medicine’ he was working in a NIH-sponsored merit research scheme at the University of Texas Health Science Centre, USA. Currently, his laboratory teaches and conducts research in ‘Molecular and Cellular Endocrinology’ with pioneering contributions in understanding the functional and mechanistic details of nuclear receptor actions in mammalian cell physiology. On the administrative front, he served as the Chairperson of the Centre for Molecular Medicine during 2007-09 and subsequently as the ‘Proctor’ of Jawaharlal Nehru University. In addition, he was appointed as the ‘Director’ at the Advanced Instrumentation Research Facility (AIRF) at JNU during 2015 to 2017. He is a recipient of gold medal by the ‘Society for Reproductive Endocrinology and Comparative Endocrinology for significant contribution in the area of ‘Molecular and Cellular Endocrinology’. During the year 2010 was been nominated as a Fellow of the National Academy of Sciences, India. He is also Editor-in-Chief of the ‘Journal of Endocrinology and Reproduction’. Presently, he is serving as a Professor at the Special Centre for Molecular Medicine. He has ~80 publications, one international patent and two Indian patents to his credit.
Molecular and Cellular Endocrinology with focus on Nuclear Receptors
The Nuclear Receptor super-family is a large group of ligand-modulated transcription factors with 48 members presently identified in the human genome. Members of this family of receptors are involved in regulation of numerous physiological and patho-physiological processes and have enormous potential as targets for the treatment of diseases such as cancer, diabetes, coronary heart disease and asthma. Nuclear Receptors, that include steroid hormone receptors, are intra-cellular transcription factors which regulate gene expression in response to their cognate ligands. They function either as homodimers or as heterodimers with retinoid X receptor (RXR). NRs are attractive targets for drug discovery because their activities can be modulated by interacting ligands and have proved to be ‘drug-responsive’. However, some newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological roles and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of actions. Towards better understanding of the functional significance of these transcription factors some of the comprehensive research projects are in progress in our laboratory. The role of two key xenobiotic receptor i.e. Pregnane & Xenobiotic Receptor (PXR), Constitutive Androstane Receptor (CAR) in metabolism and clearance of endogenous metabolites and xenobiotics (including prescription drugs) and the role of androgen/estrogen receptor mediated signaling in prostate/breast cancer progression are under investigation. In addition to above research interests, mitotic genome-bookmarking by nuclear receptors highlighting a novel dimension in epigenetic reprogramming and disease assessment has been part of an emerging concept initiated from our laboratory.
The laboratory has been supported by grants from ICMR, CSIR, DST, UGC, DBT and NASF. Currently ongoing project:
Title: Investigation into polymorphism and differential response of Thyroid Hormone Receptor (THR) by natural and synthetic small molecule modulators. Supported by Indian Council of Medical Research (ICMR).
BHU, IIT-Roorkee, National Dairy Research Institute, AIIMS-Delhi
- Rizvi S, Chhabra A, Tripathi A, Tyagi RK (2023) Mitotic genome-bookmarking by nuclear hormone receptors: A novel dimension in epigenetic reprogramming and disease assessment. Mol Cell Endocrinol. 18:112069. doi: 10.1016/j.mce.2023.112069 (in Press)
- Kashyap J, Kumari N, Ponnusamy K, Tyagi RK (2023) Hereditary Vitamin D-Resistant Rickets (HVDRR) associated SNP variants of vitamin D receptor exhibit malfunctioning at multiple levels. BBA-Gene Regulatory Mechanisms Volume 1866: 194891
- Agrawal H, Thakur K, Mitra S, Mitra D, Keswani C, Sircar D, Onteru S, Singh D, Singh SP, Tyagi RK, Roy P. (2022) Evaluation of (Anti)androgenic Activities of Environmental Xenobiotics in Milk Using a Human Liver Cell Line and Androgen Receptor-Based Promoter-Reporter Assay. ACS Omega,7:41531-41547
- Thakur K, Emmagouni Sharath Kumar Goud1, Jawa Y, Keswani C, Onteru S, Singh D, Singh SP, Roy P, Tyagi RK (2023) Detection of endocrine and metabolism disrupting xenobiotics in milk-derived fat samples by fluorescent protein-tagged nuclear receptors and live cell imaging. Toxicology Mechanisms and Methods 33:293-306.
- Kashyap J, Tyagi RK (2022) Mitotic genome bookmarking by nuclear receptor VDR advocates transmission of cellular transcriptional memory to progeny cells (2022) Experimental Cell Research 417:113193
- Saha P, Kumar S, Datta K and Tyagi RK (2021) Incidence of increased autophagy in mifepristone treated in vitro and in vivo polycystic ovarian models and its reversion upon thymoquinone treatment. Journal of Steroid Biochemistry and Molecular Biology. 208:105823
- Kumar S, Vijayan S, Dash AK, Gourinath S and Tyagi RK (2021) Nuclear Receptor SHP Dampens Transcription Function and Abrogates Mitotic Chromatin Association of PXR and ERα via Intermolecular Interactions. BBA-Gene Regulatory Mechanisms 1864:194683.
- Roy N, Verma D, Kashyap J, Tyagi RK and Prabhakar A (2020) Prototype of a smart microfluidic platform for the evaluation of SARS-CoV-2 pathogenesis, along with estimation of the effectiveness of potential drug candidates and antigen-antibody interactions in convalescent plasma therapy. Transactions of the Indian National Academy of Engineering 5: 241–250.
- Singh SK, Yende AS, Ponnusamy K and Tyagi RK (2019) A comprehensive evaluation of anti-diabetic drugs on nuclear receptor PXR platform Toxicol In Vitro 60: 347-358. (Impact factor 3.07)
- Dagar M, Singh JP, Dagar G, Tyagi RK and Bagchi G (2019) Phosphorylation of HSP90 by protein kinase A is essential for the nuclear translocation of androgen receptor. J Biol Chem 294:8699-8710.
- Rana M, Dash AK, Ponnusamy K and Tyagi RK (2018) Nuclear localization signal region in nuclear receptor PXR governs the receptor association with mitotic chromatin. Chromosome Res. 26: 255-276.
- Negi S, Singh SK, Kumar S, Kumar S and Tyagi RK (2018) Stable cellular models of nuclear receptor PXR for high-throughput evaluation of small molecules. Toxicol In Vitro. 52: 222-234.
- Dash AK, Yende AS, Jaiswal B, Tyagi RK (2017) Heterodimerization of Retinoid X Receptor with Xenobiotic Receptor partners occurs in the cytoplasmic compartment: mechanistic insights of events in living cells. Experimental Cell Research 360:337-346.
- Dash AK, Yende AS, Tyagi RK (2017) Novel application of Red Fluorescent Protein (DsRed-Express) for the study of functional dynamics of Nuclear Receptors. Journal of Fluorescence 27: 1225–1231.
- Kotiya D, Jaiswal B, Ghose S, Kaul R, Datta K and Tyagi RK (2016) Role of PXR in hepatic cancer: its influences on liver detoxification capacity and cancer progression. PLoS One 11(10):e0164087.
- Rana M, Devi S, Gourinath S, Goswami R, Tyagi RK (2016) A comprehensive analysis and functional characterization of naturally occurring non-synonymous variants of nuclear receptor PXR. Biochimica et Biophysica Acta – Gene Regulatory Mechanisms 1859: 1183–1197.
- Priyanka, Kotiya D, Rana M, Subbarao N, Puri N and Tyagi RK (2016) Transcription regulation of nuclear receptor PXR: role of SUMO-1 modification and NDSM in receptor function. Molecular and Cellular Endocrinology 420:194-207.
- Saradhi M, Kumari S, Rana M, Mukhopadhyay G and Tyagi RK (2015) Identification and interplay of sequence specific DNA binding proteins involved in regulation of human Pregnane & Xenobiotic Receptor Gene Experimental Cell Research 339:187-196.
- Kumari S, Saradhi M, Rana M, Chatterjee S, Aumercier M, Mukhopadhyay G and Tyagi RK (2015) Pregnane & Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-Jun. Experimental Cell Research 330: 398-411.
- Kumar S and Tyagi RK (2012) Androgen receptor association with mitotic chromatin - analysis with introduced deletions and disease-inflicting mutations. FEBS Journal 279:4598-4614.(journal cover article)
Prof. Suman Kumar Dhar carried out his doctoral studies (1992-98) from the School of Environmental Sciences, Jawaharlal Nehru University, New Delhi working on replication and maintenance of ribosomal DNA circle in the protozoan parasite Entamoeba histolytica. Prior to joining the Special Centre for Molecular Medicine, he worked on mammalian DNA replication as post-doctoral fellow (1998-2001) at the Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
Prof. Suman Kumar Dhar at the Special Centre for Molecular Medicine, JNU is studying replication and cell cycle control of two medically important human pathogens: Plasmodium falciparum that causes human malaria and Helicobacter pylori that causes gastric ulcer and gastric adenocarcinoma. Both these pathogens are immensely important but their biology is poorly understood. Disease control is hampered due to drug resistance and non-availability of vaccine. His main aim is to understand the complex DNA replication and cell cycle mechanisms in these pathogens with a view to identify novel targets for therapy.
His laboratory discovered a mechanism by which the unique DnaB helicase ring is loaded in H. pylori oriC without the use of DnaC, conventional helicase loader, when he identified Hp0897, an unknown ORF as the helicase loader in H. pylori. Further research from his laboratories has shown unique polar replisome and divisome assembly in H. pylori that leads to asymmetric growth of these pathogenic bacteria.
Multiple rounds of DNA replication take place during the blood stage developmental cycle of P. falciparum where 1N DNA content goes up to 16-32 N. Dr Dhar is studying the control of both organellar apicoplast DNA and nuclear DNA replication. He has functionally characterized key molecules that are essential for nuclear/organellar DNA replication. He has also discovered the presence of ARS-like DNA sequences in the Plasmodium genome and identified genome-wide distribution of replication initiation sites in these parasites. The presence of high frequency replication initiation sites in Plasmodium genome may explain the faster cycles of DNA replication in this deadly pathogen.
Using Chemical Biology approach, his laboratory has identified potent inhibitors against H. pylori and P. falciparum that has led to US and Indian patents.
- Deciphering functional role of human pathogenic bacteria Helicobacter pylori arginine decarboxylase; funded by Indian Council of Medical Research, India (2023-26).
The above proposal aims to understand the role of H. pylori arginine decarboxylase in acid response/adaptation and DNA replication leading to the possibility of using it as a therapeutic target against H. pylori
- Studies on replication and cell division of two medically important human pathogens Helicobacter pylori and Plasmodium falciparum: unique biology and finding targets for intervention; funded by Sir J. C. Bose National Fellowship, SERB, DST, Govt of India (2021-26).
Studying the H. pylori replisome and cell divisome and their coordination in the context of mammalian host cells will help to shed some insight into the interaction between the host and pathogen. These insights will have possible applications in managing H. pylori infections as inhibition of DNA replication and cell division indeed will have effect on bacterial growth and multiplication. Studying functional aspects of selected Plasmodium falciparum parasite proteins like PfORC, PfMCM, PfPCNA, PfGCN5 etc will not only help to understand the unique aspects of parasite biology ranging from parasite DNA replication, intracellular trafficking to gene regulation, it will also help to establish new target for therapy.
Dr A. Krishnamachari, Prof. Naidu Subbarao, SCIS, JNU; Dr Neelima Mondal, SLS, JNU; Prof. Pritam Mukhopadhyay, SPS, JNU, Dr Inderjeet Kaur, Central University of Haryana
Dr Asish Mukhopadhyay, NICED, Kolkata; Dr Agam P. Singh, NII, New Delhi
>80 publications, H-index: 27; Total citations >3700 (Google scholar)
Papers published from JNU as independent researcher
- Shekhar S, Verma S, Gupta MK, Roy SS, Kaur I, Krishnamachari A, Dhar SK. (2023) Genome-wide binding sites of Plasmodium falciparum mini chromosome maintenance protein MCM6 show new insights into parasite DNA replication. Biochim Biophys Acta Mol Cell Res. 1870:119546. doi: 10.1016/j.bbamcr.2023.119546. (IF: 5.0)
- Shekhar S, Bhowmick K, Dhar SK. (2022) Role of PfMYST in DNA replication in Plasmodium falciparum. Exp Parasitol. 242:108396. (IF: 2.2)
- Tehlan A, Bhowmick K, Kumar A, Subbarao N, Dhar SK. (2022) The tetrameric structure of Plasmodium falciparum phosphoglycerate mutase is critical for optimal enzymatic activity. J Biol Chem. 298:101713. (IF: 5.1)
- Purushothaman M, Dhar SK, Natesh R. (2022) Role of unique loops in oligomerization and ATPase function of Plasmodium falciparum gyrase B. Protein Sci. 31:323-332. (IF: 6.1)
- Valissery P, Thapa R, Singh J, Gaur D, Bhattacharya J, Singh AP and Dhar SK. (2020) Potent in vivo antimalarial activity of water-soluble artemisinin nano-preparations. RSC Advance. 10: 36201–36211. (IF: 3.2)
- Tehlan A, Karmakar BC, Paul S, Kumar R, Kaur I, Ghosh A, Mukhopadhyay AK, Dhar SK. (2020) Antibacterial action of acriflavine hydrochloride for eradication of the gastric pathogen Helicobacter pylori. FEMS Microbiol Lett. 367: 1-9. (IF: 2.7)
- Dana S, Valissery P, Kumar S, Gurung SK, Mondal N, Dhar SK*, Mukhopadhyay P*. (*co-corresponding author) (2020) Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity. ACS Med Chem Lett. 11:1450-1456. (IF: 4.3)
- Bhowmick K, Tehlan A, Sunita, Sudhakar R, Kaur I, Sijwali PS, Krishnamachari A, Dhar SK. (2020) Plasmodium falciparum GCN5 acetyltransferase follows a novel proteolytic processing pathway that is essential for its function. J Cell Sci. 133(1):jcs236489. (IF: 4.1)
- Kumar A, Saha A, Verma VK, Dhar SK. (2019) Helicobacter pylori helicase loader protein Hp0897 shows unique functions of N- and C-terminal regions. Biochem J. 476:3261-3279. (IF: 3.8)
- Pradhan S, Kalia I, Roy SS, Singh OP, Adak T, Singh AP, Dhar SK. (2019) Molecular characterization and expression profile of an alternate proliferating cell nuclear antigen homolog PbPCNA2 in Plasmodium berghei. IUBMB Life. 71:1293-1301. (IF: 3.5)
- Banu K, Mitra P, Subbarao N, Dhar SK. (2018) Role of tyrosine residue (Y213) in nuclear retention of PCNA1 in human malaria parasite Plasmodium falciparum. FEMS Microbiol Lett. 365(17). (IF: 2.7)
- Kamran M, Dubey P, Verma V, Dasgupta S, Dhar SK. (2018) Helicobacter pylori shows asymmetric and polar cell divisome assembly associated with DNA replisome. FEBS J. 285:2531-2547. (IF: 5.5)
- Kumar A, Dhar SK, Subbarao N. (2018) In silico identification of inhibitors against Plasmodium falciparum histone deacetylase 1 (PfHDAC-1) J Mol Model. 24: 232. (IF: 1.7)
- Sharma R, Sharma B, Gupta A, Dhar SK. (2018) Identification of a novel trafficking pathway exporting a replication protein, Orc2 to nucleus via classical secretory pathway in Plasmodium falciparum. Biochim Biophys Acta Mol Cell Res. 1865:817-829. (IF: 4.1)
- Gupta MK, Agarawal M, Banu K, Reddy KS, Gaur D, Dhar SK. (2018) Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum. Biochem Biophys Res Commun. 495:1285-1291. (IF: 3.3)
- Kumar A, Bhowmick K, Vikramdeo KS, Mondal N, Subbarao N, Dhar SK. (2017) Designing novel inhibitors against histone acetyltransferase (HAT: GCN5) of Plasmodium falciparum. Eur J Med Chem. 138:26-37. (IF: 6.1)
- Agarwal M, Bhowmick K, Shah K, Krishnamachari A, Dhar SK. (2017) Identification and characterization of ARS-like sequences as putative origin(s) of replication in human malaria parasite Plasmodium falciparum. FEBS J. 284:2674-2695. (IF: 5.5)
- Dana S, Keshri SK, Shukla J, Vikramdeo KS, Mondal N, Mukhopadhyay P, Dhar SK. (2016) Design, Synthesis and Evaluation of Bifunctional Acridinine-Naphthalenediimide Redox-Active Conjugates as Antimalarials. ACS Omega. 1:318-333. (IF: 3.3)
- Kamran M, Sinha S, Dubey P, Lynn AM, Dhar SK. (2016) Identification of putative Z-ring-associated proteins, involved in cell division in human pathogenic bacteria Helicobacter pylori. FEBS Lett. 590:2158-71. (IF: 3.5)
- Verma V, Kumar A, Nitharwal RG, Alam J, Mukhopadhyay AK, Dasgupta S, Dhar SK. (2016) Modulation of the enzymatic activities of replicative helicase (DnaB) by interaction with Hp0897: a possible mechanism for helicase loading in Helicobacter pylori. Nucleic Acids Res. 44:3288-303 (IF: 19.1)
- Deshmukh AS, Agarwal M, Dhar SK. (2016) Regulation of DNA replication proteins in parasitic protozoans: possible role of CDK-like kinases. Curr Genet. 62:481-6 (IF: 2.6)
- Narayanaswamy N, Das S, Samanta PK, Banu K, Sharma GP, Mondal N, Dhar SK, Pati SK, Govindaraju T. (2015) Sequence-specific recognition of DNA minor groove by an NIR-fluorescence switch-on probe and its potential applications. Nucleic Acids Res. 43:8651-63 (IF: 19.1)
- Mitra P, Banu K, Deshmukh AS, Subbarao N, Dhar SK. (2015) Functional dissection of proliferating-cell nuclear antigens (1 and 2) in human malarial parasite Plasmodium falciparum: possible involvement in DNA replication and DNA damage response. Biochem J. 470:115-29. (IF: 3.8)
- Deshmukh AS, Agarwal M, Mehra P, Gupta A, Gupta N, Doerig CD, Dhar SK. (2015) Regulation of Plasmodium falciparum Origin Recognition Complex subunit 1 (PfORC1) function through phosphorylation mediated by CDK-like kinase PK5. Mol Microbiol. 98:17-33. (IF 3.5)
- Narayanaswamy N, Kumar M, Das S, Sharma R, Samanta PK, Pati SK, Dhar SK, Kundu TK, Govindaraju T (2014). A Thiazole Coumarin (TC) Turn-On Fluorescence Probe for AT-Base Pair Detection and Multipurpose Applications in Different Biological Systems. Sci Rep. 4:6476. (IF 4.1)
- Srivastava S, Bhowmick K, Chatterjee S, Basha J, Kundu TK, Dhar SK. (2014) Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum. FEBS J. 281:5265-78 (IF 5.5)
- Dana S, Prusty D, Dhayal D, Gupta MK, Dar A, Sen S, Mukhopadhyay P, Adak T, Dhar SK. (2014) The potent Anti-malarial activity of Acriflavine in vitro and in vivo. ACS Chem Biol. 9:2366-73. (IF 4.5)
- Sharma A, Kamran M, Verma V, Dasgupta S, Dhar SK. (2014) Intracellular Locations of Replication Proteins and the Origin of Replication during Chromosome Duplication in the Slowly Growing Human Pathogen Helicobacter pylori. J Bacteriol. 196:999-1011. Journal cover article. (IF 2.9)
- Bhowmick K, Dhar SK. (2013) Plasmodium falciparum single-stranded DNA-binding protein (PfSSB) interacts with PfPrex helicase and modulates its activity. FEMS Microbiol Lett. 2013 Nov 23. doi: 10.1111/1574-6968. (IF 2.7)
- Abdul Rehman SA, Verma V, Mazumder M, Dhar SK1, Gourinath S1. (2013) Crystal structure and mode of helicase binding of the C-terminal domain of primase from Helicobacter pylori. J Bacteriol. 195:2826-38. (1Co-corresponding author) (IF 2.9)
- Deshmukh A, Srivastava S, Herrmann S, Gupta A, Mitra P, Gilberger TW and Dhar SK. (2012) The role of N-terminus of Plasmodium falciparum ORC1 in telomeric localization and var gene silencing. Nucleic Acids Research 40:5313-31 (IF 19.1)
- Nitharwal RG, Verma V, Subbarao N, Dasgupta S, Choudhury NR and Dhar SK. (2012) DNA binding activity of Helicobacter pylori DnaB helicase: the role of the N-terminal domain in modulating DNA binding activities. FEBS J. 279:234-50. Journal cover article. (IF. 5.5)
- Dorin-Semblat D, Carvalho TG, Nivez M, Halbert J, …Mehra P, Dhar S,…Tilley L, Doerig C. (2012) An atypical cyclin-dependent kinase controls Plasmodium falciparum proliferation rate. Kinome. 1: 4-16.
- Prusty D, Dar A, Priya R, Sharma A, Dana S, Choudhury NR, Rao NS and Dhar SK. (2010). Single-stranded DNA binding protein from human malarial parasite Plasmodium falciparum is encoded in the nucleus and targeted to the apicoplast. Nucleic Acids Res. 38:7037-53 (IF 19.1)
- Kashav T, Nitharwal R, Abdulrehman SA, Gabdoulkhakov A, Saenger W, Dhar SK*, Gourinath S*. (2009) Three-dimensional structure of N-terminal domain of DnaB helicase and helicase-primase interactions in Helicobacter pylori. PLoS One. 20: e7515. (* co-corresponding author) (IF 3.5)
- Dar A, Prusty D, Mondal N and Dhar SK. (2009) A Unique 45 Amino Acid Region in the Toprim Domain of Plasmodium falciparum Gyrase B is Essential for Its Activity. Eukaryot Cell 8: 1759-69. (IF 3.0)
- Gupta A, Mehra P, Deshmukh A, Dar A, Mitra P, Roy N and Dhar SK. (2009) Functional dissection of the catalytic carboxyl-terminal domain of human malaria parasite Plasmodium falciparum origin recognition complex subunit 1 (PfORC1). Eukaryot Cell 8: 1341-51(IF 3.0)
- Sharma A., Nitharwal RG., Singh B., Dar A., Dasgupta A and Dhar SK. (2009) Helicobacter pylori single-stranded DNA binding protein-functional characterization and modulation of H. pylori DnaB helicase activity. FEBS J. 276: 519-531 (IF 5.5)
- Gupta, A., Mehra P. and Dhar SK. (2008). Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation. Molecular Microbiology 69: 646-65. (IF 3.5)
- Prusty D., Mehra P., Srivastava S., Shivange AV., Gupta A., Roy N and Dhar SK. (2008) Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasite growth. FEMS Microbiol Lett. 282: 266-72. (IF 2.7)
- Nitharwal RG, Paul S, Soni RK, Sinha S, Prusthy D, Keshav T, RoyChoudhury N, Mukhopadhyay G, Chaudhury T, Gourinath S, and Dhar SK. (2007) The domain structure of Helicobacter pylori DnaB helicase: The N-terminal domain can be dispensable for helicase activity whereas the extreme C-terminal region is essential for its function. Nucleic Acids Res. 35: 2861-74 (IF 19.1)
- Dar MA, Sharma A, Mondal N and Dhar SK. (2007) Molecular cloning of apicoplast targeted Plasmodium falciparum DNA gyrase genes: unique intrinsic ATPase activity and ATP-independent dimerisation of PfGyrB subunit. Eukaryotic Cell. 6:398-412. (IF 3.0)
- Gupta A, Mehra P, Nitharwal R, Sharma A, Biswas AK and Dhar SK. (2006) Analogous expression pattern of Plasmodium falciparum replication initiation proteins PfMCM4 and PfORC1 during the asexual and sexual stages of intraerythrocytic developmental cycle. FEMS Microbiol. Lett. 261:12-8. (IF 2.7)
- Mehra P, Biswas AK, Gupta A, Gourinath S, Chitnis CE and Dhar SK. (2005) Expression and characterization of human malaria parasite Plasmodium falciparum origin recognition complex subunit 1. Biochem Biophys Res Commun. 337:955-66. (IF 3.3)
- Soni RK, Mehra P, Mukhopadhyay G and Dhar SK. (2005) Helicobacter pylori DnaB helicase can bypass E. coli DnaC function in vivo. Biochem J. 389(Pt 2):541-8 (IF 4.4)
- Soni RK, Mehra P, Choudhury NR, Mukhopadhyay G, Dhar SK. (2003) Functional characterization of Helicobacter pylori DnaB helicase. Nucleic Acids Res. 31:6828-40. (IF 19.1)
- Jha S, Karnani N, Dhar SK, Mukhopadhayay K, Shukla S, Saini P, Mukhopadhayay G, Prasad R. (2003). Purification and characterization of the N-terminal nucleotide binding domain of an ABC drug transporter of Candida albicans: uncommon cysteine 193 of Walker A is critical for ATP hydrolysis. Biochemistry 42:10822-32. (IF 3.0)
- Dhar, S.K$., Mondal, N., Soni, R.K., and Mukhopaddhyay, G. (2002). A ~35 kDa polypeptide from baculovirus infected insect cells binds to yeast ACS like elements in the presence of ATP. BMC Biochemistry 2002, 3:23 ($corresponding author) (IF 2.5)
- Tehlan A, Saha A and Dhar SK (2023) Targeting proteases and proteolytic processing of unusual N-terminal extensions of Plasmodium proteins: parasite peculiarity. Frontiers in Drug Discovery. 3:1223140. doi: 10.3389/fddsv.2023.1223140
- Deshmukh AS, Srivastava S, Dhar SK. (2013) Plasmodium falciparum: epigenetic control of var gene regulation and disease. Subcell Biochem. 61:659-82.
- Mitra P, Deshmukh A and Dhar SK. (2012) DNA replication during intra-erythrocytic stages of human malarial parasite Plasmodium falciparum. Current Science. 102;725-740.
- Nitharwal RG, Verma V, Dasgupta S, Dhar SK. (2011) Helicobacter pylori chromosomal DNA replication: current status and future perspectives. FEBS Lett. 585:7-17.
- Dhar, S. K$., Soni R. K., Das, B. K. and Mukhopaddhyay, G. (2003) Molecular Mechanism of Action of Major Helicobacter pylori Virulence Factors. Molecular and Cellular Biochemistry 253:207-15 ($corresponding author)
Number of students awarded/submitted Ph. D.: 28
Number of Ph. D. students currently enrolled: 8
Prof. Anand Ranganathan obtained his BSc (Hons) degree in Chemistry from St. Stephen’s College, Delhi, after which he went on a scholarship to Cambridge, UK, where he obtained his BA (Tripos) in Natural Sciences, his MA, and his PhD. After a post-doctoral stint at Cambridge, Anand returned to India to join International Centre for Genetic Engineering and Biotechnology, Delhi, where he ran his lab for 16 years as a Staff Research Scientist. In 2015 he joined the Special Centre for Molecular Medicine, Jawaharlal Nehru University, Delhi and became a full Professor in 2019. His laboratory works in the area of Directed Evolution and Pathogenesis, with special emphasis on Tuberculosis and Malaria. Scientific contributions from Anand's lab have been published in peer-reviewed journals like The Journal of Biological Chemistry, Chemistry & Biology, The Journal of Infectious Diseases, Journal of Clinical Investigation, and Nature Communications.
- Fiction: The Land of the Wilted Rose (Rupa, 2012)
- Fiction: For Love and Honour (Bloomsbury, 2015)
- Fiction: The Rat Eater (Bloomsbury, 2019)
- Fiction: Souffle (Penguin, 2023).
- Non-fiction: Hindus in Hindu Rashtra (BluOne Ink, 2023).
- Non-fiction: India’s Forgotten Scientists (Penguin, 2024 slated).
Prof. Ranganathan’s Laboratory has invented codon-shuffling, a novel method for the directed evolution of proteins, using which a de novo protein was unearthed that was able to disrupt ICAM dimerisation and block host cell invasion by both Mycobacterium tuberculosis and Plasmodium falciparum. The major objectives of this research group are as follows: 1. To study the role of host ICAMs in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum. 2. To discover new molecules for TB therapy. 3. To focus on the emergence of Plasmodium falciparum resistance and the repurposing of existing drugs against artemisinin-resistant Plasmodium falciparum. 4. To discover de-novo peptide binders against target proteins of Mycobacterium tuberculosis, Plasmodium falciparum, and Leishmania donovani.
Title: A multi-targeted approach encompassing fundamental and applied studies towards drug discovery for Leishmaniasis
Leishmaniasis is one of the major neglected tropical diseases, for which no vaccines exist. Chemotherapy is hampered by limited efficacy coupled with development of resistance and other side effects. The Leishmania-macrophage interaction provides an excellent example of co-evolution that promotes parasite survival and causes diseases. Conceivably, interfering with these processes represents a promising new strategy against Leishmania. For this, a multi targeted approach is required to get better understanding of these host pathogen interactions to develop a drug. Thus, we proposed to target four essential mechanisms of its pathogenesis to block motility, invasion, growth, sustenance inside the host macrophages.
Name of the funding agency: DST-IRHPA grant number IPA/2020/000007, Duration (From-To) 27.03.2020-27.03.2025
SCMM, JNU; THSTI, Faridabad; IIT, Delhi.
- Chaurasiya, A., Kumari, G., Garg, S., Shoaib, R., Anam, Z., Joshi, N., Kumari, J., Singhal, J., Singh, N., Kaushik, S., Kahlon, AK., Dubey, N., Maurya, MK., Srivastava, P., Marothia, M., Joshi, P., Gupta, K., Saini, S., Das, G., Bhattacharjee, S., Singh, S*., Ranganathan, A*. 2022. Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir. Antimicrob Agents Chemother. 66(12): e0039222.
- Anam, Z., Kumari, G., Mukherjee, S., Rex, DAB., Biswas, S., Maurya, P., Ravikumar, S., Gupta, N., Kushawaha, AK., Sah, RK., Chaurasiya, A., Singhal, J., Singh, N., Kaushik, S., Prasad, TSK., Pati, S., Ranganathan, A.*, Singh, S*. 2022. Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion. Front Cell Infect Microbiol. 12:924424.
- Singhal, J*., Madan, E., Chaurasiya, A., Srivastava, P., Singh, N., Kaushik, S., Kahlon, AK., Maurya, MK., Marothia, M., Joshi, P., Ranganathan, A*. and Singh, S*. 2022. Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival. Front. Cell. Infect. Microbiol. 12:878136.
- Srivastava, A., Garg, S., Karan, S., Kaushik, S., Ranganathan, A., Pati, S., Garg, LC, Singh, S. 2022. Plasmodium falciparum Antigen Expression in Leishmania Parasite: A Way Forward for Live Attenuated Vaccine Development. Methods Mol Biol. 2410:555.
- Singh, DK., Tousif, S., Bhaskar, A., Devi, A., Negi, K., Moitra, B., Ranganathan, A., Dwivedi, VP., Das, G. 2021. Luteolin as a potential host-directed immunotherapy adjunct to isoniazid treatment of tuberculosis. PLoS Pathog. 17:8.
- Chaurasiya, A., Garg, S., Khanna, A., Narayana, C., Dwivedi, VP., Joshi, N., Anam, ZE., Singh, N., Singhal, J., Kaushik, S., Kahlon, AK, Srivastava, P., Marothia, M., Kumar, M., Kumar, S., Kumari, G., Munjal, A., Gupta, S., Singh, P., Pati, S., Dag, G., Sagar, R., Ranganathan, A*., Singh, S*. 2021. Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics. Cell Death Discov. 7:10.
- Anam, ZE., Joshi, N., Gupta, S., Yadav, P., Chaurasiya, A., Kahlon, AK., Kaushik, S., Munde, M., Ranganathan, A*., Singh, S*. 2020. A De novo Peptide from a High Throughput Peptide Library Blocks Myosin A -MTIP Complex Formation in Plasmodium falciparum. Int. J. Mol. Sci. 21(17):6158.
- Singh, DK., Dwivedi, VP., Singh, SP., Kumari, A., Sharma, SK., Ranganathan, A., Van Kaer, L., Das, G. 2020. Luteolin-mediated Kv1.3 K+ channel inhibition augments BCG vaccine efficacy against tuberculosis by promoting central memory T cell responses in mice. PLoS Pathog. 16:9.
- Prakash, P., Zeeshan, M., Saini, E., Muneer, A., Khurana, S., Chourasia, BK., Deshmukh, A., Kaur, I., Dabra, S., Singh, N., Anam, Z., Chaurasiya, A., Kaushik, S., Dahiya, P., Kalamuddin, M., Thakur, JK., Mohmmed, A., Ranganathan, A.*, Malhotra, P*. 2017. Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum. Nat Commun. 8(1):1548.
- Bhalla, K., Chugh, M., Mehrotra, S., Rathore, S., Tousif, S., Dwivedi, VP., Prakash, P., Samuchiwal, SK., Kumar, S., Singh, DK., Ghanwat, S., Kumar, D., Das, G., Mohmmed, A., Malhotra, P.*, Ranganathan A*. 2015. Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum. Nat Commun. 6:6049.
Number of students awarded/submitted PhD: 13
Number of PhD students currently enrolled: 06
Umesh Chand Singh Yadav, Professor
Prof. Umesh Chand Singh Yadav is presently affiliated with the Special Centre for Molecular Medicine, JNU, New Delhi as a Professor. He has earned a Ph.D. degree in Biochemistry from School of Life Sciences, JNU. After completing his Ph.D., he worked as a postdoctoral fellow for 6 years at the University of Texas Medical Branch Galveston, USA and was promoted to the faculty position and worked for 3 years as faculty at the University of Texas Medical Branch Galveston, USA. Has was awarded Eye Research/Retina Research Foundation/ Joseph M. and Eula C. Lawrence Scholarship Travel Grant by ARVO Foundation in 2007.
He returned to India in 2013 with an award of Ramanujan Fellowship from Department of Science and Technology (DST), Govt of India and joined as Assistant Professor at the Central University of Gujarat, Gandhinagar where he ascended to the Professor position in 2020. Subsequently he moved to Jawaharlal Nehru University (JNU) and joined Special Centre for Molecular Medicine (SCMM) as a Professor.
His area of research is Metabolic Disorder & Inflammatory Diseases including Cancer, diabetes, cardiovascular diseases and lung inflammatory diseases like asthma and COPD. He has published more than 85 manuscripts, review articles and book chapters and edited two books for Springer Nature on the topics of “Oxidative stress and human diseases” and “Functional food”. He has successfully completed 4 extramurally funded projects awarded by DST/SERB, DBT, and GSBTM and executing many other extramurally funded projects at SCMM, JNU in niche areas of his expertise. He also holds an international patent on COPD and another Indian patent is filed on the treatment modalities of Endothelial dysfunction. Under his supervision eleven (11) students have been awarded Ph.D., 4 students awarded M.Phil. and many have completed post-graduate dissertations.
He is engaged in teaching the Graduate, Post-graduate and Doctoral students along with delivering lectures at different HRDCs across the country for orientation and refresher programs for teachers, and organised Faculty induction programme at HRDC, JNU in 2023. He represents in several academic and administrative committees, selection committees and has held various responsible positions such as Assistant controller of Examinations, Deputy Controller of Examinations, Nodal office for National, Academic depository, and convenor and coordinator of various academic bodies.
Prof. Umesh Chand Singh Yadav carried out his doctoral studies School of Life Sciences at Jawaharlal Nehru University, New Delhi. He pursued his research work in the area of ‘Metabolic Disorder & Inflammatory Diseases including Cancer, diabetes, cardiovascular diseases and lung inflammatory diseases like asthma and COPD’ as a Post Doctoral Fellow and faculty member at the University of Texas Medical Branch, Galveston, Texas, USA. Prior to joining the ‘Special Centre for Molecular Medicine’ in the year 2020, he was working as Professor at the Central University of Gujarat, Gandhinagar, India.
His research interest is to understand biochemical and molecular mechanism(s) of metabolic disorder-induced chronic inflammatory diseases including diabetic and cardiovascular complications, cancer, asthma and COPD through cutting edge research, and discover and develop potential mechanism-based molecular medicine for clinical intervention and therapy.
- Understanding biochemical and molecular link between obesity and Asthma
Role: Principal Investigator
Type: Fellowship Award (Ramanujan Fellowship)
Funding Agency: Department of Science and Technology (DST), Government of India
Status: Completed (Oct. 2013-Oct. 2018)
- Regulation of endothelial cells dysfunction by Erk-5 in metabolic disorder
Role: Principal Investigator
Type: Early Career Research Award
Funding Agency: SCIENCE & ENGINEERING RESEARCH BOARD (SERB)/DST, Government of India
Status: Completed (Oct. 2016-Jan. 2020)
- SREBP-mediated dysregulation of lipid homeostasis in foam cell formation
Role: Principal Investigator
Funding agency: Gujarat State Biotechnology Mission (GSBTM), DST, Govt. of Gujarat
Status: Completed (Oct. 2016-Jan. 2020)
- Synthesis of natural product congeners to reinvigorate the investigation of their chemistry & anti-inflammatory pathogenesis and anti-carcinogenic activities
Role: Joint Principal Investigator
Type: Extramural; North-East Twining Grant
Funding agency: Dept. of Biotechnology (DBT)
Status: Completed (Jan. 2017- Jan. 2020)
- Investigating the Role of RUNX2/Galectin-3 in the Pathogenesis of Cigarette Smoke Induced Lung Cancer: Identification of Novel Diagnostic Biomarker and Potential Therapeutic Target
Role: Principal Investigator
Type: Extramural (EMR)
Funding agency: Dept. of Biotechnology (DBT)
Status: Running (July 2023- July 2026)
- Study of Epigenetic Regulation of Erk5 by Histone Methylase, Enhancer of Zeste Homolog (EZH)-2 during oxLDL-induced Endothelial to Mesenchymal Transition (EndMT)
Role: Principal Investigator
Type: Extramural (CRG)
Funding agency: SERB
Status: Not started yet (Sept. 2023-Sept. 2026)
- Dr. Rajesh Vasita, Biomaterial Engineering, School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India
- Prof Rana Pratap Singh, Cancer Biology, School of Life Sciences, JNU, New Delhi, India.
- Dr. Ved Prakash Singh, Department of Industrial Chemistry, Mizoram University, Aizawl, Mizoram.
- Rajput PK, Varghese JF, Srivastava AK, Kumar U, Yadav UCS. Visfatin-induced upregulation of lipogenesis via EGFR/AKT/GSK3β pathway promotes breast cancer cell growth. Cell Signal. 107:110686. Jul. 2023. doi: 10.1016/j.cellsig.2023.110686.
- Sharma JR, Agraval H, Yadav UCS. Cigarette smoke induces epithelial-to-mesenchymal transition, stemness, and metastasis in lung adenocarcinoma cells via upregulated RUNX-2/galectin-3 pathway. Life Sci. 318:121480. Apr 2023. doi: 10.1016/j.lfs.2023.121480.
- Rajput PK, Sharma JR, Yadav UCS. Cellular and molecular insights into the roles of visfatin in breast cancer cells plasticity programs. Life Sci. 304:120706. Sept 2022. doi: 10.1016/j.lfs.2022.120706.
- Agraval H, Sharma JR, Dholia N, Yadav UCS. Air-Liquid Interface Culture Model to Study Lung Cancer-Associated Cellular and Molecular Changes. Methods Mol Biol. 2413:133-144, 2022. doi: 10.1007/978-1-0716-1896-7_14.
- Agraval H, Sharma JR, Prakash N, Yadav UCS. Fisetin suppresses cigarette smoke extract-induced epithelial to mesenchymal transition of airway epithelial cells through regulating COX-2/MMPs/β-catenin pathway. Chem Biol Interact. 351:109771, Jan 2022. doi: 10.1016/j.cbi.2021.109771.
- Varghese JF, Patel R, Singh M, Yadav UCS. Fisetin Prevents Oxidized Low-density Lipoprotein-Induced Macrophage Foam Cell Formation. J Cardiovasc Pharmacol. 78(5):e729-e737, Nov 2021. doi: 10.1097/FJC.0000000000001096.
- Dholia N, Sethi GS, Naura AS, Yadav UCS. Cysteinyl leukotriene D4 (LTD4) promotes airway epithelial cell inflammation and remodelling. Inflamm Res.70(1):109-126, Jan. 2021. doi: 10.1007/s00011-020-01416-z.
- 8. Patel R, Varghese JF, Singh RP, Yadav UCS. Induction of endothelial dysfunction by oxidized low-density lipoproteins via downregulation of Erk-5/Mef2c/Klf2 signaling: Amelioration by fisetin. Biochimie. 11; 163: 152-162, Jan 2019. doi. 10.1016/j.biochi.2019.06.007
- Varghese JF, Patel R, Yadav UCS. Sterol regulatory element binding protein (SREBP) -1 mediates oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation through NLRP3 inflammasome activation. Cellular Signalling. 53: 316-326, Jan. 2019. doi: 10.1016/j.cellsig.2018.10.020.
- Dholia N and Yadav UCS. Lipid mediator Leukotriene D4-induces airway epithelial cells proliferation through EGFR/ERK1/2 pathway. Prostaglandins Other Lipid Mediat. 136:55-63, May 2018. doi: 10.1016/j.prostaglandins.2018.05.003.
- Rani V, Deep G, Singh RK, Palle K, Yadav UCS. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies, Life Sciences, Available online 3 February 2016, ISSN 0024-3205, Feb 2016. doi: 10.1016/j.lfs.2016.02.002.
- Yadav UCS, et al., Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells. Free Radic Biol Med. 65C:15-25, Dec. 2013. doi: 10.1016/j.freeradbiomed.2013.06.008.
- Access complete PubMed list here: https://pubmed.ncbi.nlm.nih.gov/?term=yadav+ucs&sort=date
Number of students awarded/submitted Ph. D.: 11
Number of Ph. D. students currently enrolled: 2
Professor Shailja Singh
Shailja obtained her PhD in Biomedical Sciences at the University of Delhi. During her post-doctoral tenure at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Delhi, she was awarded multiple international accolades, including the Bill & Melinda Gates Foundation Travel Award for attending malaria conferences. Thereafter, Shailja joined the Department of Life Sciences at Shiv Nadar Institution of Eminence (SNIoE) as an Associate Professor, where she received prestigious awards such as the Innovative Young Biotechnologist Award (IYBA) from the Dept. of Biotechnology (DBT), Govt. of India, and the Shiv Nadar University Award and Indus Foundation Award for Research Excellence. In 2016, Shailja joined the Special Centre for Molecular Medicine, Jawaharlal Nehru University, Delhi, and successfully progressed towards attaining the position of a full professor. In recognition of her translational research in Malaria and Kala-azar, Shailja has been honored with various prestigious awards, including the Women Bioscientist Award from DBT and the Biotechnology Industry Research Assistance Council-Gandhian Young Technological Innovation Award (BIRAC-GYTIA) from the Honorable President of India. Shailja currently serves as an expert member in several regulatory bodies within the university and the Govt. of India. With 25 years of research experience, her expertise lies in molecular parasitology, focusing on understanding host-pathogen interactions in diseases like malaria and Kala-azar. Scientific contributions from Shailja’s lab have been published in esteemed peer-reviewed journals, including Nature Communications, EBioMedicine, Proceedings of the National Academy of Sciences (PNAS), Advanced Healthcare Materials, and Cell Death Discovery, among others.
Shailja exemplifies a highly successful homegrown scientist in India. Her research group focuses on understanding the fundamental and medicinal aspects of human malaria and leishmania parasites. She pioneered the identification of signaling molecules (Ca2+ and cAMP) and signal transduction pathway effectors (CDPK1, CN, PAP, DGK, PAT, PLPs, etc.) involved in malaria parasite invasion and egress. This groundbreaking work has paved the way for innovative anti-malarial medications. Shailja’s research group has significantly contributed to translational research, particularly in anti-malarial and anti-Leishmanial inhibitor screening and development. Recognized by Biotechnology Industry Research Assistance Council (BIRAC)-Gandhian Young Technological Innovation (GYTI) awards, she has developed breakthrough drug discovery tools. Furthermore, she introduced a nanomedicine-based approach using surface-coated iron-oxide-nanoparticles to enhance the efficacy of the age-old anti-malarial medication, Artesunate. In collaboration with Institut Pasteur, France, she discovered that the patatin-like phospholipase that regulates gametocyte egress has the potential to prevent malaria transmission. Notably, her recent discovery of a host erythrocyte micro-RNA, miR-197-5p, revealed an unusual, nucleotide-based therapy and inspired a novel strategy for generating anti-malarial molecular pharmaceuticals. Her research group has also identified several parasite chaperones, such as Prefoldins, Cold shock protein, and Prohibitins, while exploiting host proteins like SphK1, HSP-70, PMCA4, G6PD, LanCl2, Kell, and NMDA for antimalarial drug development.
“Evaluation of the role of S1P in Tribal Plasmodium falciparum malaria patients for its potential therapeutic consideration”
This project aims to establish the role of Sphingosine-1-Phosphate (S1P) in severe human malaria of various clinical manifestations, particularly in adult patients. Besides, the study will investigate whether genetic variations in the S1P pathway contribute to the clinical severity of malaria. Further, it will also explore the influence of S1P on critical pathogenic processes in severe malaria, such as endothelial dysfunction, inflammation, and NO production. Overall, the findings will provide clues for the prognostic implication of S1P in severe P. falciparum malaria and could support its use as an adjunctive therapeutic in severe malaria cases.
Indian Council of Medical Research (ICMR), Government of India
“A comprehensive characterization of key organellar metabolic transporters in Apicomplexa to enter in the drug discovery pipeline”
This research addresses the critical need for the development of novel and effective antimalarial compounds with limited off-target effects. Surprisingly, there is little redundancy in the Plasmodium 'Transportome' and substantial evidence that membrane transporter proteins are likely to serve as therapeutic targets. Our integrative strategy, which combines biochemical, biophysical, and molecular approaches, will allow us to identify small molecule candidates against the transport of mono-carboxylates, which is critical for parasite survival. The ultimate goal of the project is to determine whether these transporters have antimalarial, transmission-blocking, or preventive potential.
Indo-Department of Biotechnology (DBT), Government of India and Swiss National Science Foundation (SNSF), Switzerland
“A multi-targeted approach encompassing fundamental and applied studies towards drug discovery for Leishmaniasis”
Leishmaniasis is one of the major neglected tropical diseases, for which no vaccines exist. Chemotherapy is hampered by limited efficacy coupled with the development of resistance and other side effects. The Leishmania/macrophage interaction provides an excellent example of co-evolution that promotes parasite survival. Conceivably, interfering with these processes represents a promising novel strategy against Leishmania. Towards this, a multi-targeted approach is required to get a better understanding of these host-pathogen interactions to develop a drug. Here, we propose to target four essential mechanisms of Leishmania pathogenesis to block motility, invasion, growth, and sustenance inside the host macrophages.
Science and Engineering Research Board (SERB), Department of Science & Technology (DST), Government of India
NUMBER OF STUDENTS AWARDED/SUBMITTED Ph.D.: 18
NUMBER OF Ph.D. STUDENTS CURRENTLY ENROLLED: 06
Selected Publications: 148
Papers in peer-reviewed journals (in reverse chronological order; *Corresponding author)
- Sadat Shafi, Sonal Gupta, Ravi Jain, Rumaisha Shoaib, Akshay Munjal, Preeti Maurya, Purnendu Kumar, Abul Kalam Najmi, Shailja Singh*. Tackling the emerging Artemisinin-resistant malaria parasite by modulation of defensive oxido-reductive mechanism via nitrofurantoin repurposing. Biochemical Pharmacology; Sept. 2023,215, 115756. doi: 10.1016/j.bcp.2023.115756
- Atul, Preeti Chaudhary, Swati Gupta, Rumaisha Shoaib, Rahul Pasupureddy, Bharti Goyal, Bhumika Kumar, Om Prakash Singh, Rajnikant Dixit, Shailja Singh, Mymoona Akhter, Neera Kapoor, Veena Pande, Soumyananda Chakraborti, Kapil Vashisht, Kailash C Pandey. Artemisinin resistance in P. falciparum: Probing the interacting partners of Kelch13 protein in parasite. Journal of Global Antimicrobial Resistance; 2023 Aug 24; In press.
- Kashish Azeem, Mofieed Ahmed, Amad Uddin, Shailja Singh, Rajan Patel, Mohammad Abid. Comparative Investigation on Interaction of Potent Antimalarials with Human Serum Albumin via Multispectroscopic and Computational Approaches. Luminescence. 2023 Aug 31. doi: 10.1002/bio.4590.
- Miklós Bege, Vigyasa Singh, Neha Sharma, Nóra Debreczeni, Ilona Bereczki, Poonam, Pál Herczegh, Brijesh Rathi*, Shailja Singh*, Anikó Borbás*. In vitro and in vivo antiplasmodial evaluation of sugar-modified nucleoside analogues. Sci Rep. 2023 Jul 28;13(1):12228. doi: 10.1038/s41598-023-39541-4.
- Ravi Ranjan Kumar, Ravi Jain, Sabir Akhtar, Nidha Parveen, Arabinda Ghosh, Veena Sharma, Shailja Singh*. Characterization of thiamine pyrophosphokinase of vitamin B1 biosynthetic pathway as a drug target of Leishmania donovani. J Biomol Struct Dyn. 2023 Jun 23;1-17. doi: 10.1080/07391102.2023.2227718. Online ahead of print.
- Kashish Azeem, Iram Irfan, Qudsia Rashid, Shailja Singh, Rajan Patel, Mohammad Abid. Recent Updates on Interaction Studies and Drug Delivery of Antimalarials with Serum Albumin proteins. Curr Med Chem. 2023 May 9. doi: 10.2174/0929867330666230509121931.
- Deepika Kannan, Nishant Joshi, Sonal Gupta, Soumya Pati, Souvik Bhattacharjee, Gordon Langsley & Shailja Singh*. Cytoprotective autophagy as a pro-survival strategy in ART-resistant malaria parasites. Cell Death Discov. 2023 May 13;9(1):160. doi: 10.1038/s41420-023-01401-5.
- Sashi Bhusan Ojha, Raj Kumar Sah, Evanka Madan, Ruby Bansal, Shaktirekha Roy, Shailja Singh* & Gunanidhi Dhangadamajhi. Cuscuta reflexa Possess Potent Inhibitory Activity Against Human Malaria Parasite: An In Vitro and In Vivo Study. Curr Microbiol 80, 189 (2023). https://doi.org/10.1007/s00284-023-03289-x.
- Ifeoma Ezenyi, Evanka Madan, Jhalak Singhal, Ravi Jain, Amrita Chakrabarti, Gajala Deethamvali Ghousepeer, Ramendra Pati Pandey, Ngozichukwuka Igoli, John Igoli, Shailja Singh*. Screening of traditional medicinal plant extracts and compounds identifies a potent antileishmanial diarylheptanoid from Siphonochilus aethiopicus. J Biomol Struct Dyn. 2023 May 18;1-15. doi: 10.1080/07391102.2023.2212779.
- Monika Saini, Che Julius Ngwa, Manisha Marothia, Pritee Verma, Shakeel Ahmad, Jyoti Kumari, Sakshi Anand, Vandana Vandana, Bharti Goyal, Soumyananda Chakraborti, Kailash C. Pandey, Swati Garg, Soumya Pati, Anand Ranganathan, Gabriele Pradel, Shailja Singh*. Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite. Biochem Pharmacol. 2023 Jun;212:115567. doi: 10.1016/j.bcp.2023.115567.
- Ankita Behl, Rumaisha Shoaib, Fernando De Leon, Geeta Kumari, Monika Saini, Evanka Madan, Vikash Kumar, Harshita Singh, Jyoti Kumari, Preeti Maurya, Swati Garg, Prakash Chandra Mishra, Christoph Arenz, Shailja Singh*. Targeting essential plasmodium cold shock protein to block growth and transmission of malaria parasite. iScience. 2023 Apr 11;26(5):106637. doi: 10.1016/j.isci.2023.106637.
- Nidhi Kirtikumar Bub, Sakshi Anand, Swati Garg, Vishal Saxena, Dhanabala Subhiksha Rajesh Khanna, Deeptanshu Agarwal, Sanjay Kumar Kochar, Shailja Singh*, Shilpi Garg. Plasmodium Iron-Sulfur [Fe-S] cluster assembly protein Dre2 as a plausible target of Artemisinin: Mechanistic insights derived in a prokaryotic heterologous system. Gene. 2023 Mar 28;869:147396. doi: 10.1016/j.gene.2023.147396.
- Raj Kumar Sah, Sakshi Anand, Waseem Dar, Ravi Jain, Geeta Kumari, Evanka Madan, Monika Saini, Aashima Gupta, Nishant Joshi, Rahul Singh Hada, Nutan Gupta, Soumya Pati, Shailja Singh*. Host-Erythrocytic Sphingosine-1-Phosphate Regulates Plasmodium Histone Deacetylase Activity and Exhibits Epigenetic Control over Cell Death and Differentiation. Microbiol Spectr. 2023 Feb 6;e0276622. doi: 10.1128/spectrum.02766-22.
Dr. Souvik Bhattacharjee, Associate Professor
Dr. Souvik Bhattacharjee carried out his doctoral studies the CSIR-Institute of Microbial Technology, Chandigarh. He pursued his research work in the area of ‘Protein trafficking in malaria-infected erythrocytes and the mechanism of artemisinin-resistance’, firstly as a post-doctoral fellow at Northwestern University, Chicago, and then as Research Assistant Professor at the University of Notre Dame, Indiana. Prior to joining the ‘Special Centre for Molecular Medicine’ in 2015, he was working in artemisinin-resistance mechanisms Plasmodium falciparum at the University of Notre Dame, USA.
The research in my laboratory is directed towards the elucidation of targeting signals that sort proteins destined for localization within the different compartments in the host-pathogen interface. Primarily, we are looking in Plasmodium falciparum as the human pathogen, and Phytophthora infestans as the plant pathogen. We trace the evolutionary convergence in the virulent protein trafficking mechanisms across pathogens of different origin and we characterize essential motifs using transgenic approaches. Our other area of interest involves understanding the contribution of host factors towards the development of artemisinin-resistance in P. falciparum.
- Translating the Phylogenetic affinities between a plant pathogenic oomycete Phytophthora infestans and a human pathogen Plasmodium falciparum to reveal evolutionary convergence in virulence secretion using in-silico, proteomic and metabolomic approaches. (DST-SERB CRG/2021/000238).
- Elucidating the role of clinical anemia in the induction of artemisinin resistance in Plasmodium falciparum. (ICMR; 58/25/2020/PHA/BMS).
- Unravelling the molecular mechanisms underlying human ABO blood type preference by the virulence RIFIN variants in Plasmodium falciparum-infected erythrocyte rosettes. (MoE STARS Project ID: 2023-0111).
IIT-Delhi; RCB, Faridabad, University of Notre Dame, USA;
- Hari Madhav, Tarosh S. Patel, Zeba Rizvi, G. Srinivas Reddy, Abdur Rahman, Md. Ataur Rahman, Saiema Ahmedi, Sadaf Fatima, Kanika Saxena, Nikhat Manzoor, Souvik Bhattacharjee, Bharat C. Dixit, Puran Singh Sijwali, Nasimul Hoda. Development of diphenylmethylpiperazine hybrids of chloroquinoline and triazolopyrimidine using Petasis reaction as new cysteine proteases inhibitors for malaria therapeutics. European Journal of Medicinal Chemistry. Volume 258, 5 October 2023, 115564.
- Kannan D, Joshi N, Gupta S, Pati S, Bhattacharjee S, Langsley G, Singh S. Cytoprotective autophagy as a pro-survival strategy in ART-resistant malaria parasites. Cell Death Discov. 2023 May 13; 9(1):160. doi: 10.1038/s41420-023-01401-5.
- Pal K, Raza Md. K, Legac J, Rahman A, Manzoor S, Bhattacharjee S, Rosenthal PJ and Hoda N. Identification, in-vitro anti-plasmodial assessment and docking studies of series of tetrahydrobenzothieno[2,3-d]pyrimidine-acetamide molecular hybrids as potential antimalarial agents. European Journal of Medicinal Chemistry. Volume 248, 15 February 2023, 115055
- Chaurasiya A, Kumari G, Garg S, Shoaib R, Anam Z, Joshi N, Kumari J, Singhal J, Singh N, Kaushik S, Kahlon AK, Dubey N, Maurya MK, Srivastava P, Marothia M, Joshi P, Gupta K, Saini S, Das G, Bhattacharjee S, Singh S, Ranganathan A. Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir. Antimicrob Agents Chemother. 2022 Dec 20;66(12): e0039222. doi: 10.1128/aac.00392-22. Epub 2022 Nov 14. PMID: 36374050
- Goel N, Dhiman K, Kalidas N, Mukhopadhyay A, Ashish F, Bhattacharjee S. Plasmodium falciparum Kelch13 and its artemisinin-resistant mutants assemble as hexamers in solution: a SAXS data-driven modelling study. FEBS J. 2022 Jan 28. doi: 10.1111/febs.16378. Online ahead of print. PMID: 35092154.
- Kumar T, Maitra S, Rahman A, Bhattacharjee S. A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum. PLoS Pathog. 2021 Nov 15;17(11): e1009595. doi: 10.1371/journal.ppat.1009595.
- Nayak A, Saxena H, Bathula C, Kumar T, Bhattacharjee S, Sen S and Gupta A. Diversity‑oriented synthesis derived indole based spiro and fused small molecules kills artemisinin‑resistant Plasmodium falciparum. Malar J (2021) 20:100. https://doi.org/10.1186/s12936-021-03632-2.
- Kannan D, Yadav N, Ahmad S, Namdev P, Bhattacharjee S, Lochab B and Singh S. Pre-clinical study of iron oxide nanoparticles fortified artesunate for efficient targeting of malarial parasite. EBioMedicine. 2019 Jul; 45:261-277. doi: 10.1016/j.ebiom.2019.06.026.
- Bhattacharjee S, Coppens I, Mbengue A, Suresh N, Ghorbal M, Slouka Z, Safeukui I, Tang HY, Speicher DW, Stahelin RV, Mohandas N, Haldar K. Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance. Blood. 2018 Mar 15;131(11):1234-1247.
- Haldar K, Bhattacharjee S, Safeukui I. Drug resistance in Plasmodium. Nat Rev Microbiol. 2018 Mar;16(3):156-170. doi: 10.1038/nrmicro.2017.161. Epub 2018 Jan 22. Review.
- Alassane Mbengue, Souvik Bhattacharjee*, Trupti Pandharkar, Haining Liu, Guillermina Estiu, Robert V. Stahelin, Shahir Rizk, Dieudonne L. Njimoh, Yana Ryan, Kesinee Chotivanich, Chea Nguon, Mehdi Ghorbal, Jose-Juan Lopez-Rubio, Michael Pfrender , Scott Emrich, Narla Mohandas, Arjen M. Dondorp, Olaf Wiest and Kasturi Haldar. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520, 683–687 (30 April 2015). *Equal contributing author.
- Bhattacharjee S, Stahelin RV, Speicher KD, Speicher DW, Haldar K. Endoplasmic Reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell. 2012 Jan 20; 148(1-2): 201-12.
Number of students awarded/submitted Ph. D.: 04
Number of Ph. D. students currently enrolled: 04
Dr. Vijay Pal Singh Rawat, Associate Professor
Dr Vijay Pal Singh Rawat did his Ph.D in human biology from Ludwig Maximilians University (LMU), Munich, Germany with Summa cum laude ("with highest honor"). During his doctoral studies he identified and characterized the leukemia specific genetic and molecular alterations and their functional role in leukemia initiation and progression. Dr Rawat demonstrated for the first time that the activation of a proto-oncogene - in this case CDX2 - by a chromosomal translocation can be the key step in myeloid leukemogenesis, even if the fusion gene is generated and expressed in parallel. Before joining JNU, Dr Rawat worked as an Assistant Professor and Principal Scientist at University of Ulm, Germany and Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, Germany, where his research group analysed the functional role of stem cell regulatory genes, epigenetic factors and recently discovered epigenetic marks 5hmC in cancer development, progression and identify potential drug target for leukaemia treatment. Dr. Rawat joined the Special Centre for Molecular Medicine, JNU in January 2021.
Dr. Rawat is working on cancer, cancer stem cell and hematopoiesis. The key focuses of Dr Rawat’s research is a) Identifying and characterizing cancer-patient-specific genetic/epigenetic and molecular alterations and their functional role in cancer initiation and progression, b) Establishing mouse and humanized mouse models of leukemia by using stem/progenitors transplantation model to identify novel drug targets for leukemia treatment and to assay drug screening. c) Characterization of the functional role of epigenetic factors in stem cell ageing and cancer stem cell (CSC). Dr Rawat has profound experience in establishing cancer models using lentivirus/retrovirus based vector system and lentiviral-mediated CRISPR/Cas9 genome editing system which is evident from his research work published in high ranking international journals (PNAS, Blood, Leukemia, JCI, Cancer Cell etc, please see the CV for details). Currently, Dr Rawat’s laboratory is interested in the following areas-
A. Identification and characterization the functional role of DNA demethylating enzymes in acute leukemia and solid cancer
B. Determining the role of epigenetic modifier Tet dioxygenase and 5-hydroxymethyl-cytosine modifications in normal stem cell ageing and cancer stem cell
C. Characterization of the role of small non-coding RNA and RNA binding proteins in cancer development and normal stem cells
D. Development of strategies to antagonize the leukemogenic potential of the homeobox genes in acute leukemia
- Title: Characterizing the functional role of DNA binding domain lacking novel alternative splice form of TET1 in acute myeloid leukemia, leukemic stem cells and can it be chemically targeted. Funding agency: ICMR
- Title: Uncovering the novel oncogenic role of Thymine DNA Glycosylase epigenetic function in acute leukemia is a potential therapeutic target for acute leukemia treatment. Funding agency: SERB-DST
- Title: Characterizing the oncogenic role of TET3 and associated epigenetic marks 5-hydorxymethylcytosine in gene regulation and pathogenesis of acute myeloid leukemia. Funding agency: SERB-DST
Prof. Ritu Gupta, AIIMS, New Delhi. Prof. Rana P Singh, SLS, JNU, New Delhi. Prof. Dr. med. Christian Buske, Director, Institute of Experimental Cancer Research, Ulm, Germany.
Prof. Dr. med. Michaela Feuring, Department of Internal Medicine III, University Hospital Ulm, Germany
Selected Publications: (in last five years)
- Bamezai S, Pulikkottil AJ, Yadav T, Naidu VM, Mueller J, Mark J, Mandal T, Feder KA, Lehle S, Song C, Rosler R, Wiese S, Hoell JI, Kloetgen A, Karsan A, Kumari A, Wojenski L, Sinha AU, Gonzalez-Menendez I, Quintanilla-Martinez L, Donato E, Trumpp A, Kruse E, Hamperl S, Zou L, Rawat VPS *, Buske C*. A non-canonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML. Blood. July 2023, 6;142(1):90-105. (IF: 25)
- Pulikkottil AJ Bamezai S, Ammer T, Mohr F, Feder K, Vegi NM, Mandal T, Kohlhofer U, Quintanilla-Martínez L, Singh A, Buske C*, Rawat VPS*. TET3 promotes AML growth and epigenetically regulates glucose metabolism and leukemic stem cell associated pathways. Leukemia, Feb. 2022, 36(2):416-425.. (IF: 12.5)
- Bamezai S, Demir D, Pulikkottil A, Ciccarone F, Fischbein E, Sinha A, Borga C, Kronnie Gt, Meyer LH, Mohr F, Götze M, Caiafa P, Debatin KM, Döhner K, Döhner H, Menendez I, Quintanilla-Martínez L, Herold T, Jeremias I, Feuring-Buske M, Buske C*, Rawat VPS*. TET1 acts as pro-leukemic factor in human T-cell acute lymphoblastic leukemia and can be antagonized via PARP inhibition. Leukemia, Feb;35(2):389-403, 2021. (IF: 12.5)
- Rawat VPS*≠, Götze M≠, Rasalkar A, Vegi NM, Ihme S, Thoene S, Pastore A, Bararia D, Döhner H, Döhner K, Feuring-Buske M, Quintanilla-Fend L, Buske C*. The microRNA miR-196b acts as tumor suppressor in Cdx2 driven acute myeloid leukemia. Haematologica. 2020 Jun;105(6):e285-e289 ( IF: 10.2)
- Thoene S, Mandal T, Vegi NM, Quintanilla-Martinez L, Rösler R, Wiese S, Metzeler KH, Herold T, Haferlach T, Döhner K, Döhner H, Schwarzmüller L, Klingmüller U, Buske C, Rawat VPS*, Feuring-Buske M*. The ParaHox gene Cdx4 induces acute erythroid leukemia in mice. Blood Adv. 2019 Nov 26;3(22):3729-3739. ( IF: 7.63)
Number of students awarded/submitted Ph. D.: 2
Number of Ph. D. students currently enrolled: 4
Dr. Saima Aijaz, Assistant Professor
Dr. Saima Aijaz received her Ph.D degree from the Indian Institute of Science, Bangalore, India where she worked on the outer capsid protein of rotavirus to evaluate its potential as a recombinant vaccine candidate. During her post-doctoral work at University College London (United Kingdom), she worked on the functional characterization of proteins associated with epithelial tight junctions. After joining SCMM, Dr. Aijaz started investigating the effect of tight junction disruption on the pathogenesis of intestinal infections caused by Enteropathogenic E. coli as well as in rare diseases such as retinitis pigmentosa type 12.
1. Regulation of the tight junction barrier in Enteropathogenic E. coli infections
2. Disruption of the Tight Junctions in Retinitis Pigmentosa Type-12
Tight junctions seal adjacent epithelial cells to selectively regulate paracellular permeability and prevent the intermixing of apical and basolateral proteins of the plasma membrane. Regulation of paracellular permeability is a critical function of tight junctions and increased permeability is associated with diverse disease conditions ranging from bacterial and viral infections to cancer and metastasis. Research in the laboratory is focused on the molecular mechanisms that regulate the disruption of tight junctions in epithelial cells in response to pathologic stimuli. In one approach, Enteropathogenic E. coli (EPEC) is used as a model system to study the regulation of paracellular permeability. EPEC disrupts epithelial tight junctions and is a leading cause of diarrhea in the developing world causing significant morbidity and mortality due excessive permeability of water and electrolytes through the intestinal tight junctions. However, the underlying mechanisms that cause the drastic increase in permeability through intestinal junctions have not been elucidated yet. The laboratory is engaged in the identification of tight junction-based signaling pathways that regulate the EPEC-mediated leakage through tight junctions with the ultimate goal of identifying molecules to block/reverse this leakage. In another approach, work is being carried out to understand how defects in the tight junctions of retinal pigmented epithelia prevent the normal functioning of the retina in retinitis pigmentosa type 12.
1. Restoration of the intestinal barrier in Enteropathogenic E. coli infections: Lysosome and cytoskeleton pathways as novel drug targets (PI). (2020-2024). Funded by MHRD-STARS
The aim of this project is to identify whether modulation of the host cell lysosomal machinery can prevent leakage through intestinal tight junctions.
2. Mechanisms of retinal degeneration in Retinitis Pigmentosa Type 12: Role of the Crumbs homology proteins-1 and -2 (PI). (2020-2023). Funded by ICMR.
This project is designed to understand how defects in the Crumbs homology proteins-1 and -2 cause retinitis pigmentosa type 12.
- Aijaz, S. (2020). Tracing the origins of the novel coronavirus SARS-CoV-2. JNU-ENVIS. 25 (1):19-20
- Singh A.P., Sharma S., Pagarware K., Siraji R. A., Ansari I., Mandal A., Walling P. and Aijaz S. (2018). Enteropathogenic E. coli effectors EspF and Map independently disrupt tight junctions through distinct mechanisms involving transcriptional and post-transcriptional regulation. Scientific Reports 8: 3719
- Singh AP and Aijaz S (2016). Enteropathogenic E. coli:Breaking the intestinal tight junction barrier. F1000Research. 4:231.
- Singh AP and Aijaz S (2015). Generation of a MDCK cell line with constitutive expression of the Enteropathogenic E. coli effector protein Map as an in vitro model of pathogenesis. Bioengineered. 6(6): 335-341.
- Nie M, Aijaz S, Leefa Chong San IV, Balda MS, Matter K. (2009). The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription. EMBO Reports 10:1125-1131.
- Aijaz S, Sanchez-Heras E, Balda MS, Matter K. (2007). Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2. BMC Cell Biology, 8:49.
- Aijaz S, Balda MS, Matter K. (2006) Tight junctions: Molecular architecture and function. International Reviews in Cytology; 248: 261-298.
- Matter K, Aijaz S, Tsapara A, Balda MS. (2005) Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Current Opinion in Cell Biology; 17(5): 453-458.
- Aijaz S, D'Atri F, Citi S, Balda MS, Matter K. (2005). Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signalling and G1/S phase transition. Developmental Cell; 8(5): 777-786.
Number of students awarded Ph.D: 7
Number of Ph.D students currently enrolled: 3
Dr. Dipankar Ghosh, Assistant Professor
Dipankar Ghosh carried out his doctoral studies in Jadavpur University, Kolkata. He pursued his postdoctoral research in Immunology and Infectious Diseases in the Cleveland Clinic, Ohio USA, where their group discovered the post-translational processing and functions of human defensin 5 (HD5) in innate immune response. For this he won the Berlin Bumpus Investigator award in the USA. Subsequently he worked in the Indian Institute of Technology (IIT), Kharagpur, before joining SCMM.
We work on early host-microbe interactions, that ultimately define the predisposition and/or outcomes of diseases. The human epithelial surface is continuously exposed to microbes. This epithelium presents the first line of defence against external threats. This defence is not physical barrier alone; but extremely complex array of receptors, signalling cascades and effectors that are key to innate immunity. We are interested to understand how epithelial and innate immune cells interact with themselves and bacteria to exert this innate immunity. For this we study nutrition, microbiota and biofilms with specific emphasis on Quorum signalling and the cross talk with innate immune determinants. These studies help to contribute to the understanding of lethal multiple drug resistant nosocomial infections and sepsis, especially neonatal sepsis which kills thousands of babies in early life. We are currently part of the National Neonatal Sepsis Research Consortium (DBT), one of the largest research programs in India in collaboration with AIIMS, TSHTI, IGIB, NII and ICGEB.
Ongoing Projects: 1
Prof. Sanjoy K. Bhattacharya, Bascom Palmer Eye Institute, Florida, U.S.A (Lipidomics).
The Indian Neonatal Sepsis Consortium (AIIMS-Del, NII, ICGEB, TSHTI, IGIB & IIIT).
Prof. Rakesh Lodha, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi (Hospital Associated Infections).
Dr. Venkat Panchagnula, National Chemical Laboratory, Pune (Laser Desorption Ionization Mass Spectrometry).
- Lahiri P., Gogoi P., and Ghosh D. (2023) Single-Step Capture and Targeted Metabolomics of Alkyl-Quinolones in Outer Membrane Vesicles (OMVs) of Pseudomonas aeruginosa. Methods Mol Biol 2625, 201-2016.
- Pompilio A, Crocetta V, Ghosh D et al. (2016) Stenotrophomonas maltophilia phenotypic and genotypic diversity during a 10-year colonization in the lungs of a cystic fibrosis patient. Frontiers in Microbiology 2016; 7: 1551
- Pluháček T, Lemr K, Ghosh D, Milde D, Novák J and Havlíček V (2016) Characterization of Microbial Siderophores by Mass Spectrometry. Mass spectrometry Reviews. 35: 35-47
- Ghosh D., Salzman NH, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature. 422:522-6.Commentary: Ganz T. Microbiology: Gut defence. Nature. 422:478-9.
- Ghosh D., Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat. Immunol. 3:583-590. Commentary: Zasloff M. Trypsin, for the defense. Nat Immunol. 2002 Jun;3(6):508-10.
Recent Peer Reviewed Journals/Books
- Ghosh, D. (2011). Pathogenesis of Malabsorption Syndrome: Issues on Gut Flora and Innate Immunity. In: Ghoshal, U Malabsorption Syndrome in Tropics. Delhi: Elsevier. 179-204.
- Ghosh, D. (2010). Probiotics and Intestinal Defensins: Augmenting the First Line of Defense in Gastrointentinal Immunity. In: Nair, G. B. and Takeda, Y. Probiotic Foods in Health and Disease. Delhi: Oxford & IBH Publishing Co. 61-74
Patents (if any)
- Selective Detection and Analysis of Small Molecules Ghosh D., Dharware D. and Panchagnula V. Jawaharlal Nehru University, New Delhi and Central Scientific and Industrial Research (CSIR), New Delhi. (Ind) 407/DEL/2011; (EPO) EP2676287A2 ; (USPTO) 20130323849A1. Technology Ready for Transfer.
Number of students awarded/submitted Ph. D.: 1
Number of Ph. D. students currently enrolled: 4