Kasper Karlsson
Assistant Professor
E-mail: kasper.karlsson@ki.se
Visiting address: SciLifeLab Alfa 5 Tomtebodavägen 23 B, 17165 Solna
Postal address: K7 Onkologi-Patologi, K7 Forskning Kallioniemi Karlsson, 171 77 Stockholm
About me
- We develop new experimental and computational models to study tumor evolution
at single cell and single subclone level, in order to better predict drug
response for pediatric cancers
Dr Karlsson received his PhD at Karolinska Institutet under the supervision
of professor Sten Linnarsson, where he was trained in the fields of molecular
diagnostics and single-cell technologies. Specifically, he developed methods
to sequence cell-free DNA without amplification in order to make more
accurate predictions for non-invasive prenatal testing, and examined isoform
expression in single cells.
During his postdoctoral work, his focus shifted to studies of tumor biology.
In the laboratories of professors Christina Curtis and Calvin Kuo at Stanford
University, Dr. Karlsson developed an organoid based experimental model to
study early tumor evolution. Here he also co-developed several tools,
including an expressed cellular barcoding system and a microwell platform to
better quantify tumor subclone dynamics during evolution and under drug
perturbations.
Dr Karlsson became an Assistant professor at Karolinska Institutet in March
2021.
2020 Swedish Childhood Cancer Foundation, Project Grant
2020 Swedish Childhood Cancer Foundation, Research Assistant Grant
2018 Stanford Center for Cancer Systems Biology (CCSB) Pilot project
2018 Postdocs at the Interface, Stanford University, ChEM-H
2018 Swedish Research Council, International Postdoc Grant
2017 Stanford School of Medicine Dean’s Postdoctoral Fellowship
2003 - 2009, Master of Science, Industrial Engineering, the Royal Institute
of Technology, Sweden
2011 - 2016, PhD in Medicine, Karolinska Instiutet, Sweden
2016 - 2021, Postdoc, Stanford University, USA
Research
- I am an systems biologist with expertise in developing new models to study
tumor evolution at single cell and single tumor subclone level. Specifically,
my research aims at developing new experimental and computational tools for
solid pediatric cancers to predict drug response that take intra-tumoral
heterogeneity into account.
It is well known that intratumoral heterogeneity is important for cancer
evolution and the development of drug resistance. It has been shown that even
cells located in close spatial proximity in the tumor, can exhibit large
variation in drug response. Thus, to achieve a lasting therapeutic response,
each tumor subclone needs to be addressed adequately. However, this
fundamental aspect of tumor biology is often overlooked when new therapies
are being developed, because it is difficult to model and address
intratumoral heterogeneity. For example, most drug response studies use cell
line models, which are known to be homogenous, and bulk sequencing data that
fails to distinguish between different tumor subclones. We believe this is an
important reason for the high failure rate of new compounds entering clinical
trials, and why many new therapies only show a modest extension of life
compared to standard of care.
To study intratumoral heterogeneity we apply state-of-the-art organoid 3D
models, that better preserve tumor heterogeneity compared to 2D cell lines.
Furthermore, we have developed several tools, including an expressed cellular
barcode system that marks the genome if individual cells with a unique DNA
barcode. Daughter cells inherit the barcode, and this can be used for lineage
tracing. With this system we can track thousands of unique tumor subclones
and also assess their phenotype by single cell sequencing. We have also
developed a microwell system to track thousands of single cell derived
organoids over time, and methods to extract e.g. drug resistant organoids for
further characterization. The lab collaborates closely with experts in
computational modeling of tumor evolution and AI/machine learning labs to
develop quantitative models of drug prediction that takes intra-tumoral
heterogeneity into account. We also work closely with clinicians to
facilitate clinical implementation of identified combinatorial therapies for
pediatric cancer.
Articles
- Journal article: CELL SYSTEMS. 2023;14(9):764-776.e6
- Article: NATURE. 2023;618(7964):383-393
- Article: CANCER DISCOVERY. 2021;11(6):1562-1581
- Article: CELL. 2018;175(7):1972-1988.e16
- Article: STEM CELL RESEARCH AND THERAPY. 2017;8(1):250
- Article: MOLECULAR SYSTEMS BIOLOGY. 2017;13(5):930
- Article: BLOOD. 2017;129(7):e13-e25
- Article: BMC GENOMICS. 2017;18(1):126
- Article: GENOMICS. 2015;105(3):150-158
- Article: NATURE METHODS. 2011;9(1):72-74
All other publications
- Review: NATURE CANCER. 2020;1(8):761-773
Grants
- Swedish Research Council1 July 2018 - 28 February 2021
Employments
- Assistant Professor, Department of Oncology-Pathology, Karolinska Institutet, 2021-2025
Degrees and Education
- Degree Of Doctor Of Philosophy, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 2016