Vanessa Lundin group - Blood Engineering
Our work aims to uncover biophysical regulators of human hematopoiesis and lies at the interface of stem cell biology, biomaterial science and tissue engineering.
Research Program
We are interested in learning how cells communicate and interact with cells and matrix in their microenvironment, and how we can exploit these mechanisms to control cell fate and steer lineage formation. Specifically, the goal is to understand how molecular mediators of mechanical forces and extrinsic cues in hematopoietic niches direct blood formation in health and disease.
To model hematopoiesis in the lab, we are using directed differentiation of human induced pluripotent stem cells (iPSCs). These cells can be readily expanded and specified into the various hematopoietic lineages, hence providing an excellent tool to study blood generation and create patient-specific disease models. However, the full potential of iPSCs in modeling physiology and blood disorders is often limited by inefficient and incomplete differentiation in vitro. We propose that traditional cell culture methods fail to provide necessary biophysical stimuli. To address this, we are engineering the cellular and architectural features of human bone marrow, thereby establishing iPSC-based culture systems that recapitulate in vivohematopoiesis and promote adult blood maturation. In order to present cells with a more physiologically relevant milieu, the group is integrating concepts and tools from polymer science, microfluidics and 3D cell culture. The biomechanical signaling cascades identified in these state-of-the-art culture systems are targets for further investigation using biochemical modulators in combination with genetic approaches.
Group leader
Vanessa Lundin has a background in bioengineering and is an expert in stem cell regulation using bioengineering approaches. She was recruited to start her own research group at the Center for Hematology and Regenerative Medicine in 2018.
Vanessa earned her Ph.D. in 2014 under the supervision of Dr. Ana Teixeira from the Department of Cell and Molecular Biology at Karolinska Institutet, followed by a post-doc with Professor George Daley at Harvard Medical School and Boston Children’s Hospital.
Group members
For his Ph.D. project, Jonas Thier is working on the development of a 3D cell culture system for the generation of iPSC-derived red blood cells from healthy donors and MDS patients.
After completing his Bachelor’s degree in Biochemistry at the Friedrich-Schiller-University Jena in 2017, Jonas enrolled in the consecutive Master’s program specializing in Immunology, Tumor- and Stem Cell Biology. He first joined the Vanessa Lundin group for an Erasmus+ traineeship in 2019 and completed his masters project in the lab in 2021.
In his spare time he enjoys being in the outdoors, snowboarding, hiking and mountain biking.
For her Ph.D. project, Katharina Kirchhof is investigating the role of RUNX1 in healthy hematopoiesis, and how RUNX1 germline variants can cause disease. To this end, she uses iPSC from healthy donors as well as patients with RUNX1 germline variants to model embryonic hematopoiesis as well as megakaryopoiesis.
Katharina completed a Bachelors degree of Cells and Systems Biology at the University of Oxford in 2020 and then moved to Karolinska Institutet for a Master’s in Biomedicine. She first joined the Lundin lab for her Master’s thesis in 2022.
In her spare time, Katharina likes to hike, swim and play D&D.
Alumni
- David Cabrerizo Granados, Post Doc
Selected Publications
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The clinical phenotype of germline RUNX1 mutations in relation to the accompanying somatic variants and RUNX1 isoform expression. Cabrerizo Granados D, Barbosa I, Baliakas P, Hellström-Lindberg E, Lundin V.
Genes, Chromosomes and Cancer 2023;1–6. - YAP Regulates Hematopoietic Stem Cell Formation in Response to the Biomechanical Forces of Blood Flow.
LundinV#, Sugden WW#, TheodoreLN#, SousaP, Han A, Chou S, Wrighton PJ, CoxAG, Ingber DE, Goessling W, Daley GQ, North TE. Developmental Cell 2020: 52(4) 446-460.e5. #Equal contribution.
- Reconstruction of complex single-cell trajectories using CellRouter.
Lummertz da Rocha E, Rowe GR#, Lundin V#, Malleshaiah M, Jha D, Rambo CR, Li H, Collins JJ, Daley GQ. Nature Communications 2018; 9(1):892. #Equal contribution.
- Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation.
Mills R, Taylor-Weiner H, Correia JC, Agudelo LZ, Allodi I, Kolonelou C, Martinez-Redondo V, Ferreira DMS, Nichterwitz S, Comley LH, Lundin V, Hedlund E, Ruas JL, Teixeira AI. Molecular Metabolism 2018; 7: 12-22.
- Spatial control of membrane receptor function using ligand nanocalipers.
Shaw A#, Lundin V#, Petrova E, Fördős F, Benson E, Al-Amin A, Herland A, BlokzijlA, Högberg B, Teixeira AI. Nature Methods 2014; 11: 841-846. #Equal contribution.
- CtBPs sense microenvironmental oxygen levels to regulate neural stem cell state.
Dias JM, Ilkhanizadeh S, Karaca E, Duckworth JK, Lundin V, Rosenfeld MG, Ericson J, Hermanson O, Teixeira AI. Cell Reports 2014, Aug; 8(3):665-670.
- Control of Neural Stem Cell Survival by Electroactive Polymer Substrates.
Lundin V, Herland A, Berggren M, Jager EWH, Teixeira AI. PLoS One 2011; 6(4):e18624.