A living root bridge near Nongriat village, Meghalaya, India.
(generally considered as an ingenious local bioengineering solution)
Research
How do cells process information to make specific decisions?
A cell’s transition from one functional state to another is fundamental to development and disease. Cells have evolved molecular networks to sense and process the external environmental or internal state information to make specific decisions. We are particularly interested in understanding how cells use the signalling and transcriptional networks for cell fate decisions. Twin motivations drive our research: to understand the nature and function of networks and apply this knowledge to either control or engineer (reprogram) cells, such as creating better stem cells or driving the cells away from a disease state.
We use pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and pancreatic cancer as model systems for our research. To better elucidate the logic and principles of decision making, we use combinations of methods based in biochemistry, cell biology, systems biology, single-cell transcriptomics, computational biology and mathematical modelling. As a result, the lab members come from diverse fields. We strive to provide an interdisciplinary collaborative environment to pursue science.
We are currently pursuing specific projects focused on the following themes:
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Pluripotent stem cell heterogeneity and its significance
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Cell state specific configuration and reconfiguration of regulatory networks
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Information flow through cell signaling networks
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Cellular reprogramming to generate cells with totipotency
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Cell type specific regulation of gene expression
People
Current members
Thulaj Meharwade, M.Sc.
thulaj.meharwade@ircm.qc.ca
Ph.D. Student, Biochemistry
University of Montreal
Loick Joumier, M.Sc.
loick.joumier@ircm.qc.ca
Ph.D. Student, Bioinformatics
University of Montreal
Gilberto Duran Bishop, M.Sc.
gilberto.duran.bishop@ircm.qc.ca
Ph.D. Student, Biochemistry
University of Montreal
Sabin Dhakal, M.Sc.
sabin.dhakal@ircm.qc.ca
Research Assistant
Sanidhya Jagdish, B.Sc.
sanidhya.jagdish@ircm.qc.ca
M.Sc. Student, Experimental Medicine
McGill University
Mohammed Usama Patel, B.Sc.
mohammed.usama.patel@ircm.qc.ca
M.Sc. Student, Experimental Medicine
McGill University
Mohan Malleshaiah, Ph.D.
mohan.malleshaiah@ircm.qc.ca
Associate Research Professor
Montreal Clinical Research Institute (IRCM)
Department of Biochemistry and Molecular Medicine
University of Montreal
Melanie Candido
melanie.candido@ircm.qc.ca
Administrative Assistant
Alumni
Maxime Parisotto, Research Associate (2022)
Montreal Clinical Research Institute (IRCM).
Vivian Huynh, Master's Student (2022)
Molecular Biology, University of Montreal.
Victoria Forest, B.Sc. Intern Student (2021)
Bioinformatics, University of Montreal.
Maya DeCruz, B.Sc. Intern Student (2021)
Bioengineering, McGill University.
Amruta Sahoo, Master's Student (2021)
Bioinformatics, University of Montreal.
Fariha Anika, B.Sc. Intern Student (2020)
Computer Science, McGill University.
Abicumaran Uthamacumaran, B.Sc. Intern Student (2020)
Physics, Concordia University.
Loick Joumier, Master's Student (2019)
Bioinformatics, University of Montreeal.
Adrien Sprumont, Master's Student (2019)
Molecular Biology, University of Montreal.
Papers
Cross-activation of the FGF, NODAL and WNT pathways constrains BMP-signaling-mediated induction of the totipotent state in mouse embryonic stem cells.
Meharwade, T., Joumier, L., Parisotto, M., Huynh, V., da Rocha, E.L., and Malleshaiah, M.
Cell Reports (2023), May 30;42(5):112438. DOI: 10.1016/j.celrep.2023.112438
Single-cell mass cytometry analysis reveals stem cell heterogeneity.
Meharwade T, Joumier L, Parisotto M and Malleshaiah M.
Methods (2022). 10;208:9-18. DOI: 10.1016/j.ymeth.2022.09.009
The NAMPT inhibitor FK866 increases metformin sensitivity in pancreatic cancer cells.
Parisotto M, Vuong NH, Kalegari P, Meharwade T, Joumier L, Bourdeau V, Rowell MC, Pollak M, Malleshaiah M, Schmitzer AR, Ferbeyre G.
Cancers (2022). 14(22):5597. DOI: 10.3390/cancers14225597
Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.
Karo-Atar, D., Ouladan, S., Javkar, T., Joumier, L., Matheson, M.K., Merritt, S., Westfall, S., Rochette, A., Gentile, M.E., Fontes, G., Fonseca, G. J., Parisien, M., Diatchenko, L., von Moltke, J., Malleshaiah, M., Gregorieff, A. and King, I. L.
Journal of Experimental Medicine (2022). 219 (9):e20212311. DOI: 10.1084/jem.20212311
Cross-activation of the FGF, TGF-β and WNT pathways constrains BMP4-mediated induction of the Totipotent state in mouse embryonic stem cells.
Meharwade, T., Joumier, L., Parisotto, M., Huynh, V., da Rocha, E.L., and Malleshaiah, M.
bioRxiv (2022), 2022.2004.2015.488509; doi: https://doi.org/10.1101/2022.04.15.488509.
Direct reprogramming of the intestinal epithelium by parasitic helminths subverts type 2 immunity.
Karo-Atar, D., Ouladan, S., Javkar, T., Joumier, L., Matheson, M.K., Merritt, S., Westfall, S., Rochette, A., Gentile, M.E., Fontes, G., Fonseca, G. J., Parisien, M., Diatchenko, L., von Moltke, J., Malleshaiah, M., Gregorieff, A. and King, I. L.
bioRxiv (2021), 2021.2009.2025.461778; doi: https://doi.org/10.1101/2021.09.25.461778.
Trajectory algorithms to infer stem cell fate decisions.
Edroaldo Lummertz da Rocha and Mohan Malleshaiah.
Computational Stem Cell Biology, Springer Nature (2019).
Reconstruction of complex single-cell trajectories using CellRouter.
Lummertz da Rocha E, Rowe RG, Lundin V, Malleshaiah M, Jha D, Rambo CR, Li H, North TE, Collins JJ, Daley GQ.
Nature Communications (2018).
Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells.
Sugimura R, Jha DK, Han A, Soria-Valles C, de Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ.
Nature (2017).
Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation.
Malleshaiah M, Padi M, Rué P, Quackenbush J, Martinez-Arias A, Gunawardena J.
Cell Reports (2016).
Cybernetics, Redux: An Outside-In Strategy for Unraveling Cellular Function.
Malleshaiah M, Gunawardena J.
Developmental Cell (2016).
Real-time protein-fragment complementation assays for studying temporal, spatial and spatiotemporal dynamics of protein–protein interactions in living cells.
Malleshaiah M, Tchekanda E and Michnick SW.
Cold Spring Harbor Laboratory Protocols (2016).
In-vivo detection of binary PKA network interactions upon activation of endogenous GPCRs.
Röck R, Bachmann V, Bhang HE, Malleshaiah M, Raffeiner P, Mayrhofer JE, Tschaikner PM, BisterK, Aanstad P, Pomper MG, Michnick SW, Stefan E.
Scientific Reports (2015).
PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades.
Stefan E, Malleshaiah MK, Breton B, Ear PH, Bachmann V, Beyermann M, Bouvier M, Michnick SW.
Nature Communications (2011).
Protein-fragment complementation assays for large-scale analysis, functional dissection and dynamic studies of protein-protein interactions in living cells.
Michnick SW., Ear PH., Landry C., Malleshaiah M. and Messier V.
Methods in Molecular Biology (2011)
The Ste5 scaffold protein directly controls a switch-like mating decision in yeast.
Malleshaiah M, Shahrezaei V, Swain PS & Michnick SW.
Nature (2010).
A Toolkit of Protein-Fragment Complementation Assays for Studying and Dissecting Large-Scale and Dynamic Protein–Protein Interactions in Living Cells.
Michnick SW., Ear PH., Landry C., Malleshaiah M. and Messier V.
Methods in Enzymology (2010)
A novel genetic screen implicates Elm1 in the inactivation of the yeast transcription factor SBF.
Manderson EN, Malleshaiah M, Michnick SW.
PLoS One (2008).
Contact
We are constantly looking for talented students and postdoctoral fellows to join our interdisciplinary collaborative team. Interested candidates, with an inclination for quantitative systems biology, should email Mohan Malleshaiah by including a Letter of Interest, full CV and contact information for upto three references.
Inquiries regarding master's and doctoral training should be directed to the following graduate programs:
Department of Biochemistry and Molecular Medicine, University of Montreal.
Molecular Biology, University of Montreal.
MAILING ADDRESS
Montreal Clinical Research Institute (IRCM)
110 Pine Avenue West,
Room 2750
Montreal, Quebec H2W 1R7
Canada
PHONE NUMBERS
Lab Phone 514-987-5633
Melanie Candido 514-987-5639
(administrative assistant)
Mohan Malleshaiah Office 514-987-5733
COMMUNITY
Montreal Clinical Research Institute (IRCM)
Department of Biochemistry and Molecular Medicine
Faculty of Medicine, University of Montreal
Division of Experimental Medicine, McGill University
Funding sources of our research
