AIST-INDIA Diverse Assets & Applications International Laboratory

Research Project

We have originally cloned two proteins, Mortalin and CARF, that are enriched in cancer cells and hence are proposed as targets for anti-cancer drugs. Currently, we are engaged in validation of (i) their role in stress, senescence and cancer biology, (ii) predictive value in stress and cancer diagnosis and (iii) use of their inhibitors (synthetic and natural) for stress and cancer intervention.

We have developed a mouse model of MCI that expresses amyloid-β protein oligomers. And are using it we search for substances that prevent disease and elucidate the mechanisms by which non-drug interventions such as exercise can improve cognitive function.

Based on the knowledge and technology relating to epigenomics and glycobiology, we are developing disease models for neurological and psychiatric disorders and constructing efficacy and toxicity evaluation systems for drugs.

We challenge in analysis of mechanical functions of novel cancer markers, nestin and CLIC1, involved in metastasis and development of diagnostic and therapeutic techniques targeting these markers.

Results

• Prasad, K;Kaul, SC; Wadhwa, R; Guruprasad, KP; Satyamoorthy, K.
  Cellular oxidative stress and sirtuins mediate regulation of senescence and neuronal differentiation by withaferin A.
  FREE RADIC BIOL MED. 2025 Mar 26:S0891-5849(25)00188-1. doi:10.1016/j.freeradbiomed.2025.03.038
• Radhakrishnan, N; Kaul, SC; Wadhwa, R; Yang, LW; Sundar, D.
  Establishing a General Atomistic Model for the Stratum Corneum Lipid Matrix Based on Experimental Data for Skin Permeation Studies.
  INT J MOL SCI. 2025 Jan 15;26(2):674. doi:10.3390/ijms26020674
• Zhang, H; Kim, H; Yuan, T; Zhang, Z; Kaul, SC; Wadhwa, R.
  Molecular Characterization of Cancer Preventive and Therapeutic Potential of Three Antistress Compounds, Triethylene Glycol, Withanone, and Withaferin A.
  INT J MOL SCI. 2025 Jan 9;26(2):493. doi:10.3390/ijms26020493
• Prasad, K; Raghu, KS; Maruthiyodan, S; Wadhwa, R; Kaul, SC; Satyamoorthy, K; Guruprasad, KP.
  Promotion of cellular differentiation and DNA repair potential in brain cancer cells by Shankhpushpi, (Clitoria ternatea L.) with rasayana properties in vitro.
  J AYURVEDA INTEGR MED. 2025 Jan 10;16(1):101050. doi:10.1016/j.jaim.2024.101050
• Yamagishi, A; Tokuoka, R; Imai, K; Mizusawa, M; Susaki, M; Uchida, K; Kijima, ST; Nagasaki, A; Takeshita, D; Yoshikawa, C; Uyeda, TQP; Nakamura, C.
  Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces.
  CELLS. 2025 Jan 17;14(2):138. doi:10.3390/cells14020138
• Hossain, AS; Clarin, MTRDC; Kimura, K; Biggin, G; Taga, Y; Uto, K; Yamagishi, A; Motoyama, E; Narenmandula; Mizuno, K; Nakamura, C; Asano, K; Ohtsuki, S; Nakamura, T; Kanki, S; Baldock, C; Raja, E; Yanagisawa, H.
  Fibrillin-1 G234D mutation in the hybrid1 domain causes tight skin associated with dysregulated elastogenesis and increased collagen cross-linking in mice.
  MATRIX BIOL. 2024 Nov 28:S0945-053X(24)00142-2. doi:10.1016/j.matbio.2024.11.006
• Kaushal, S; Gupta, S; Shefrin, S; Vora, DS; Kaul, SC; Sundar, D; Wadhwa, R; Dhanjal, JK.
  Synthetic and Natural Inhibitors of Mortalin for Cancer Therapy.
  CANCERS (Basel). 2024 Oct 13;16(20):3470. doi: 10.3390/cancers16203470
• Wadhwa, R; Wang, J; Shefrin, S; Zhang, H; Sundar, D; Kaul, SC.
  Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling.
  CANCERS (Basel). 2024 Sep 5;16(17):3090. doi: 10.3390/cancers16173090
• Shi, Y; He, H; Zhang, H; Yuan, T; Zhang, Z; DeSilva, R; Ishida, Y; Terao, K; Kaul, SC; Wadhwa, R.
  Cyclodextrin-assisted Aqueous Extract of Cinnamon for Cancer and Stress Management.
  CURR TOP MED CHEM. 2024 Aug 20. doi: 10.2174/0115680266309291240808114508
• Wadhwa, R; Yang, S; Meidinna, HN; Sari, AN; Bhargava, P;Kaul, SC.
  Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells.
  Cancers (Basel). 2024 Jun 17;16(12):2239. doi: 10.3390/cancers16122239
• Wadhwa, R; Hegde, M; Zhang, HY; Kaul, A; Wang, J; Ishida, Y; Terao, K; Kunnumakkara, AB; Kaul, SC.
  Antistress and Antiaging Potentials of Alpha-Lipoic Acid: Insights from Cell Culture-Based Experiments.
  APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY. 2024 Jun 28. doi: 10.1007/s12010-024-04994-4
• Tomita, T; Wadhwa, R; Onishi, Y.
  Natural Compounds that Modulate Circadian Rhythms.
  CURR TOP MED CHEM. 2024 May 30. doi: 10.2174/0115680266300569240514101800
• Kumar, V; Sari, AN; Gupta, D; Ishida, Y; Terao, K; Kaul, SC; Vrati, S; Sundar, D; Wadhwa, R.
  Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester.
  CURR TOP MED CHEM. 2024 Jan 24. doi: 10.2174/0115680266280720231221100004
• Kumar, V; Meidinna, HN; Kaul, SC; Gupta, D; Ishida, Y; Terao, K; Vrati, S; Sundar, D; Wadhwa, R.
  Molecular insights to the anti-COVID-19 potential of α-, β- and γ-cyclodextrins.
  J BIOMOL STRUCT DYN. 2023 Dec 20:1-11. doi: 10.1080/07391102.2023.2294385
• Zhang, HY; Zhang, ZY; Kaul, SC; Wadhawa, R.
  Antistress activity of some phytochemicals: screening, identification, validation, and potential applications.
  ANNALS OF NUTRITION AND METABOLISM. 2023;79 (suppl 1) 1087-1087; AUG. doi: 10.1159/000530786
• Viswan, A; Yoshikawa, C; Yamagishi, A; Furuhata, Y; Kato, Y; Yamazaki, T; Nakamura, C.
  Efficient genome editing by controlled release of Cas9 ribonucleoprotein in plant cytosol using polymer-modified microneedle array.
  BIOCHEM BIOPHYS RES COMMUN. 2023 Oct 29;686:149179. doi: 10.1016/j.bbrc.2023.149179
• Kumar, V; Dhanjal, JK; Sari, AN; Khurana, M; Kaul, SC; Wadhwa, R; Sundar, D.
  Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on DNA Methyltransferases: Potential in Epigenetic Cancer Therapy.
  CURR TOP MED CHEM. 2023 Jul 26. doi: 10.2174/1568026623666230726105017
• Kalra, RS; Chaudhary, A; Omar, A; Li, X; Khurana, M; Kaul, SC, Wadhwa, R.
  Stress-induced changes in CARF expression serve as a quantitative predictive measure of cell proliferation fate.
  EXP CELL RES. 2023 Jun 3:113669. doi: 10.1016/j.yexcr.2023.113669
• Huifu, H; Shefrin, S; Yang, S; Zhang, Z; Kaul, SC; Sundar, D; Wadhwa, R.
  Cucurbitacin-B inhibits cancer cell migration by targeting mortalin and HDM2: computational and in vitro experimental evidence.
  J BIOMOL STRUCT DYN. 2023 May 2:1-10. doi: 10.1080/07391102.2023.2206914
• Zhang, H; Wang, J; Prakash, J; Zhang, Z; Kaul, SC; Wadhwa, R.
  Three-way Cell-based Screening of Antistress Compounds: Identification, Validation, and Relevance to Old-age Related Pathologies.
  J GERONTOL A BIOL SCI MED SCI. 2023 Apr 15:glad103. doi: 10.1093/gerona/glad103
• Kumar, V; Sari, AN; Meidinna, HN; Kaul, A; Basu, B; Ishida, Y; Terao, K; Kaul, SC; Vrati, S; Sundar, D; Wadhwa, R.
  Computational and experimental evidence of the anti-COVID-19 potential of honeybee propolis ingredients, caffeic acid phenethyl ester and artepillin c.
  PHYTOTHER RES. 2023 Feb 9. doi: 10.1002/ptr.7717
• Huang, T; Sato, Y; Kuramochi, A; Ohba, Y; Sano, M; Miyagishi, M; Tateno, H; Wadhwa, R; Kawasaki, K; Uchida, T; Ekdahl, KN; Nilsson, B; Chung, UI; Teramura, Y.
  Surface modulation of extracellular vesicles with cell-penetrating peptide-conjugated lipids for improvement of intracellular delivery to endothelial cells.
  REGEN THER. 2023 Jan 11;22:90-98. doi: 10.1016/j.reth.2022.12.007
• Yu, Y; Zhang, GX; Li, ZP; Wang, J; Liu, Y; Bhardwaj, R; Wadhwa, R; Nagao, Y; Shichiri, M; Gao, R.
  Designed fabrication of active tumor targeting covalent organic framework nanotherapeutics via a simple post-synthetic strategy.
  NANO RESEARCH. 03 January 2023. doi: 10.1007/s12274-022-5265-7
• Shefrin, S; Sari, AN; Kumar, V; Zhang, H; Meidinna, HN; Kaul, SC; Wadhwa, R; Sundar, D.
  Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53(Ser46) mutant.
  CURR RES STRUCT BIOL. 2022 Sep 13;4:320-331. doi: 10.1016/j.crstbi.2022.09.002
• Meidinna, HN; Shefrin, S; Sari, AN; Zhang, H; Dhanjal, JK; Kaul, SC; Sundar, D; Wadhwa, R.
  Identification of a new member of Mortaparib class of inhibitors that target mortalin and PARP1.
  FRONT CELL DEV BIOL. 2022 Sep 12;10:918970. doi: 10.3389/fcell.2022.918970
• Yamagishi, A; Mizusawa, M; Uchida, K; Iijima, M; Kuroda, S; Fukazawa, K; Ishihara, K; Nakamura, C.
  Mechanical detection of interactions between proteins related to intermediate filament and transcriptional regulation in living cells.
  BIOSENS BIOELECTRON. 2022 Aug 6;216:114603. doi: 10.1016/j.bios.2022.114603
• Yoon, AR; Wadhwa, R; Kaul, SC; Yun, CO.
  Why is Mortalin a Potential Therapeutic Target for Cancer.
  FRONT CELL DEV BIOL. 2022 Jun 29;10:914540. doi: 10.3389/fcell.2022.914540
• Viswan, A; Yamagishi, A; Hoshi, M; Furuhata, Y; Kato, Y; Makimoto, N; Takeshita, T; Kobayashi, T; Iwata, F; Kimura, M; Yoshizumi, T; Nakamura, C.
  Microneedle Array-Assisted, Direct Delivery of Genome-Editing Proteins Into Plant Tissue.
  FRONT PLANT SCI. 2022 Jun 24;13:878059. doi: 10.3389/fpls.2022.878059
• Radhakrishnan, N; Kaul, SC; Wadhwa, R; Sundar, D.
  Phosphatidylserine Exposed Lipid Bilayer Models for Understanding Cancer Cell Selectivity of Natural Compounds: A Molecular Dynamics Simulation Study.
  MEMBRANES 12 (1);doi: 10.3390/membranes12010064 JAN
• Malik, V; Radhakrishnan, N; Kaul, SC; Wadhwa, R; Sundar, D.
  Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone.
  BIOMOLECULES 12 (2);doi: 10.3390/biom12020212 FEB
• Sari, AN; Dhanjal, JK; Elwakeel, A; Kumar, V; Meidinna, HN; Zhang, H; Ishida, Y; Terao, K; Sundar, D; Kaul, SC; Wadhwa, R.
  A Low Dose Combination of Withaferin A and Caffeic Acid Phenethyl Ester Possesses Anti-Metastatic Potential In Vitro: Molecular Targets and Mechanisms.
  CANCERS (Basel). 2022 Feb 3;14(3):787. doi: 10.3390/cancers14030787
• Malik, V; Kumar, V; Kaul, SC; Wadhwa, R; Sundar, D.
  Potential of Withaferin-A, Withanone and Caffeic Acid Phenethyl ester as ATP-competitive inhibitors of BRAF: A bioinformatics study.
  CURR RES STRUCT BIOL. 2021 Nov 18;3:301-311. doi: 10.1016/j.crstbi.2021.11.004
• Kaul, A; Kuthethur, R; Ishida, Y; Terao, K; Wadhwa, R; Kaul, SC.
  Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C.
  MOLECULES. 2021 Dec 23;27(1):80. doi: 10.3390/molecules27010080
• Hori, K; Yoshimoto, S; Yoshino, T; Zako, T; Hirao, G; Fujita, S; Nakamura, C; Yamagishi, A; Kamiya, N.
  Recent advances in research on biointerfaces: From cell surfaces to artificial interfaces.
  J BIOSCI BIOENG. 2022 Jan 5:S1389-1723(21)00331-5. doi: 10.1016/j.jbiosc.2021.12.004
• Radhakrishnan, N; Dhanjal, JK; Sari, AN; Ishida, Y; Terao, K; Kaul, SC; Sundar, D; Wadhwa, R.
  Caffeic acid phenethyl ester (CAPE) confers wild type p53 function in p53(Y220C) mutant: bioinformatics and experimental evidence.
  DISCOVER ONCOLOGY 12 (1);doi: 10.1007/s12672-021-00461-2 DEC 20
• Wang, J; Zhang, H; Kaul, A; Li, K; Priyandoko, D; Kaul, SC; Wadhwa, R.
  Effect of Ashwagandha Withanolides on Muscle Cell Differentiation.
  BIOMOLECULES. 2021 Oct 4;11(10):1454. doi: 10.3390/biom11101454
• Kumar, V; Sari, AN; Meidinna, HN; Dhanjal, JK; Subramani, C; Basu, B; Kaul, SC; Vrati, S; Sundar, D; Wadhwa, R.
  Computational and in vitro experimental analyses of the anti-COVID-19 potential of Mortaparib and MortaparibPlus.
  BIOSCI REP. 2021 Oct 29;41(10):BSR20212156. doi: 10.1042/BSR20212156
• Bhargava, P; Mahanta, D; Kaul, A; Ishida, Y; Terao, K; Wadhwa, R; Kaul, SC.
  Experimental Evidence for Therapeutic Potentials of Propolis.
  NUTRIENTS. 2021 Jul 24;13(8):2528. doi: 10.3390/nu13082528
• Kumar, A; Konar, A; Garg, S; Kaul, SC; Wadhwa, R.
  Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs.
  NEUROCHEMISTRY INTERNATIONAL 149; doi: 10.1016/j.neuint.2021.105124
• Kaul, Z; Cheung, CTY; Bhargava, P; Sari, AN ; Yu, Y; He, HF; Bid, H; Henson, JD; Groden, J; Reddel, RR; Kaul, SC; Wadhwa, R.
  Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells.
  SCI REP. 2021 Aug 23;11(1):17052. doi: 10.1038/s41598-021-96096-y
• Elwakeel, A; Sari, AN; Dhanjal, JK; Meidinna, HN; Sundar, D; Kaul, SC; Wadhwa, R.
  Mutant p53(L194F) Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to Mortaparib(Plus), a Multimodal Small Molecule Inhibitor.
  CANCERS (Basel). 2021 Jun 18;13(12):3043. doi: 10.3390/cancers13123043
• Yamagishi, A; Ito, F; Nakamura, C.
  Study on Cancer Cell Invasiveness via Application of Mechanical Force to Induce Chloride Ion Efflux.
  ANAL CHEM. 2021 Jun 21. doi: 10.1021/acs.analchem.1c01589
• Tomita, T; Wadhwa, R; Kaul, SC; Kurita, R; Kojima, N; Onishi, Y.
  Withanolide Derivative 2,3-Dihydro-3β-methoxy Withaferin-A Modulates the Circadian Clock via Interaction with RAR-Related Orphan Receptor α (RORa.
  J NAT PROD. 2021 Jun 21. doi: 10.1021/acs.jnatprod.0c01276
• Dhanjal, JK; Kumar, V; Garg, S; Subramani, C; Agarwal, S; Wang, J; Zhang, H; Kaul, A; Kalra, RS; Kaul, SC; Vrati, S; Sundar, D; Wadhwa, R
  Molecular mechanism of anti-SARS-CoV2 activity of Ashwagandha-derived withanolides
  Int J Biol Macromol. 2021 Jun 9:S0141-8130(21)01215-0. doi: 10.1016/j.ijbiomac.2021.06.015
• Li, X; Wang, J; Zhang, H; Xiao, L; Lei, Z; Kaul, SC; Wadhwa, R; Zhang, Z.
  Low Dose of Fluoride in the Culture Medium of Cordyceps militaris Promotes Its Growth and Enhances Bioactives with Antioxidant and Anticancer Properties.
  J FUNGI (Basel). 2021 Apr 28;7(5):342. doi: 10.3390/jof7050342
• Kalra, RS; Kumar, V; Dhanjal, JK; Garg, S; Li, X; Kaul, SC; Sundar, D; Wadhwa, R.
  COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: insights from computational and biochemical assays.
  J BIOMOL STRUCT DYN. 2021 Apr 2:1-14. doi: 10.1080/07391102.2021.1902858