Bio

Dr. Thulaj Meharwade is a postdoctoral fellow at the Stanford Cardiovascular Institute with research interests in Inflammaging, disease modeling, cellular heterogeneity and drug discovery. Dr. Meharwade received his PhD in Biochemistry from the University of Montreal, after conducting thesis work on signalling and transcriptional mechanisms regulating cell fate heterogeneity and totipotent stem cells.

Honors & Awards

  • “Public Service Award” for contributions made through Early Career Advisory Committee (ECAC), ISSCR (2025)
  • “Bourse De Fin D'études Doctorales”, Canada., University of Montreal (2023)
  • “GSCN Travel Award”, Germany., German Stem Cell Network, sponsored by Bio-Techne (2023)
  • “IUBMB Travel Award”, USA., International Union of Biochemistry and Molecular Biology (2023)
  • “Stem Cell Network Travel Award”, Canada., Till & McCulloch Meetings (2023)
  • “Bourse De Rayonnement Scientifique Travel Award”, Canada., University of Montreal (2022)
  • “Emmanuel Triassi Scholarship”, Canada., Montreal Clinical Reserch Institute (2021)
  • “Hommage Jacques Gauthier Scholarship”, Canada., Montreal Clinical Research Institute (2020)
  • “FESP-International Tuition Fees Exemption Scholarship”, Canada., University of Montreal (2019)
  • “FESP-Scholarship of Excellence”, Canada., University of Montreal (2019)
  • “GATE-Life Science”, India., Ministry of Human Resources and Development (2016)
  • “TNSET”, lifetime eligibility to join as an Assistant Professor in Tamil Nadu, India., Annamalai University (2016)
  • “Somayajula Surya Prakash Rao Memorial Scholarship”, India., Loyola College (2012)
  • “Loyola Empowerment and Reach-out Network”, India., Loyola College (2011)

Stanford Advisors

Contact

  • Academic
    dthulaj@stanford.edu
    University - Scholar Department: Cardiovascular Institute Operations Position: Postdoctoral Scholar

Additional Info

All Publications

  • Cross-activation of FGF, NODAL, and WNT pathways constrains BMP-signaling-mediated induction of the totipotent state in mouse embryonic stem cells CELL REPORTS Meharwade, T., Joumier, L., Parisotto, M., Huynh, V., da Rocha, E., Malleshaiah, M. 2023; 42 (5): 112438

    Abstract

    Embryonic stem cells (ESCs) are an attractive model to study the relationship between signaling and cell fates. Cultured mouse ESCs can exist in multiple states resembling distinct stages of early embryogenesis, such as totipotent, pluripotent, primed, and primitive endoderm. The signaling mechanisms regulating the totipotent state and coexistence of these states are poorly understood. Here we identify bone morphogenetic protein (BMP) signaling as an inducer of the totipotent state. However, we discover that BMP's role is constrained by the cross-activation of FGF, NODAL, and WNT pathways. We exploit this finding to enhance the proportion of totipotent cells by rationally inhibiting the cross-activated pathways. Single-cell mRNA sequencing reveals that induction of the totipotent state is accompanied by suppression of primed and primitive endoderm states. Furthermore, reprogrammed totipotent cells we generate in culture resemble totipotent cells of preimplantation embryo. Our findings reveal a BMP signaling mechanism regulating both the totipotent state and heterogeneity of ESCs.

    View details for DOI 10.1016/j.celrep.2023.112438

    View details for Web of Science ID 000990371100001

    View details for PubMedID 37126449

  • Single-cell mass cytometry analysis reveals stem cell heterogeneity. Methods (San Diego, Calif.) Meharwade, T., Joumier, L., Parisotto, M., Malleshaiah, M. 2022; 208: 9-18

    Abstract

    Cellular heterogeneity is fundamental to both developmental differentiation and disease establishment. Recent advances in high-throughput single-cell technology have been rapidly revolutionizing the resolution of our understanding of development and disease. However, while the study of single-cell transcriptomes is easily accessible, the analysis of single-cell proteomes is still in its infancy. In this study, we describe simultaneous profiling of multiple regulatory proteins at a single-cell level using mass cytometry or cytometry by time of flight. We develop mass cytometry reagents to study key transcription factors, signaling proteins and chromatin modifiers that regulate mouse embryonic stem cells. Our data reveal that the protein level of stem cell regulators significantly varies and that cell signaling pathways are extensively cross-activated across defined culture conditions of embryonic stem cells. In addition, the mass cytometry data enabled us to identify distinct multiple cell states of embryonic stem cells and determine their variation across culture conditions. We discuss the mass cytometry method, our results of the multi-protein analysis in embryonic stem cells and potential future perspectives for single-cell protein analysis.

    View details for DOI 10.1016/j.ymeth.2022.09.009

    View details for PubMedID 36229002

  • The NAMPT Inhibitor FK866 Increases Metformin Sensitivity in Pancreatic Cancer Cells CANCERS Parisotto, M., Vuong-Robillard, N., Kalegari, P., Meharwade, T., Joumier, L., Igelmann, S., Bourdeau, V., Rowell, M., Pollak, M., Malleshaiah, M., Schmitzer, A., Ferbeyre, G. 2022; 14 (22)

    Abstract

    Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use has been associated with reduced pancreatic cancer incidence and better survival in diabetics. Metformin has been shown to inhibit PDAC cells growth and survival, both in vitro and in vivo. However, clinical trials using metformin have failed to reduce pancreatic cancer progression in patients, raising important questions about molecular mechanisms that protect tumor cells from the antineoplastic activities of metformin. We confirmed that metformin acts through inhibition of mitochondrial complex I, decreasing the NAD+/NADH ratio, and that NAD+/NADH homeostasis determines metformin sensitivity in several cancer cell lines. Metabolites that can restore the NAD+/NADH ratio caused PDAC cells to be resistant to metformin. In addition, metformin treatment of PDAC cell lines induced a compensatory NAMPT expression, increasing the pool of cellular NAD+. The NAMPT inhibitor FK866 sensitized PDAC cells to the antiproliferative effects of metformin in vitro and decreased the cellular NAD+ pool. Intriguingly, FK866 combined with metformin increased survival in mice bearing KP4 cell line xenografts, but not in mice with PANC-1 cell line xenografts. Transcriptome analysis revealed that the drug combination reactivated genes in the p53 pathway and oxidative stress, providing new insights about the mechanisms leading to cancer cell death.

    View details for DOI 10.3390/cancers14225597

    View details for Web of Science ID 000887064200001

    View details for PubMedID 36428689

    View details for PubMedCentralID PMC9688551

https://orcid.org/0000-0002-2660-9549