Spatio-Temporal Dynamics of Tumorigenesis

Dr. Johnny Kim

Johnny Kim is a molecular biologist appointed as Independent Junior Group Leader at the Institute for Lung Health (ILH), Justus-Liebig University Giessen (JLU), Germany. He heads the research group Spatio-temporal Dynamics of Tumorigenesis.

Johnny Kim was born in Toronto, Canada. He studied biochemistry at the University of Greifswald, Germany and obtained his Diploma in Biochemistry and Molecular Biology from the University of Hamburg in 2003. He then moved to the lab of Thorsten Hoppe at the Center for Molecular Neurobiology Hamburg (ZMNH) where he worked on ubiquitin-dependent protein degradation in development and disease. In 2008 Johnny Kim received his PhD (summa cum laude) for which he received the Gebhard-Koch Prize for outstanding thesis. In 2009, he then joined the Department of Cardiac Remodelling directed by Thomas Braun at the Max Planck Institute for Heart and Lung Research (MPI-HLR) in Bad Nauheim, Germany. During this time, he pioneered the integration of genetics and functional genomics of the primary regenerative muscle compartment. For his early career achievements, he was awarded several fellowships and start-up grants from the Excellence Cluster Cardio-Pulmonary System (ECCPS) and the Center for Cell and Gene Therapy (LOEWE-CGT). Since 2013 Johnny Kim runs a research group within the Department of Cardiac Remodelling at the MPI-HLR. Dr. Kim is a committee member of the International Max Planck Research School graduate program in Molecular Organ Biology (IMPRS-MOB), elected speaker of the Academy of the Excellence cluster Cardio-Pulmonary Institute (CPI) and is a member of the German Center for Cardiovascular Research (DZHK). He published 30 research articles in well-renowned scientific journals including Science Advances, Cell Stem Cell, Cell Metabolism, Cell Reports, Nature Cell Biology, Nature Chemical Biology and Nature Communications.

The Kim lab aims to understand the molecular and multicellular demands that enable tissue maintenance in health and how defects thereof lead to cellular transformation and tumorigenesis. In addition, Dr. Kim’s lab aims to unveil the molecular mechanisms that infer inter-tumoral and intra-tumoral heterogeneity supporting therapeutic resistance and tumor progression. To this end the Kim lab integrates advanced genetic engineering coupled with systems biological pipelines to resolve multicellular and molecular dynamics of cellular transformation.

Tumors are not homogeneous collections of malignant cells. They contain different cell types including, but not limited to, neoplastic cells, infiltrating endothelial, immune, and stromal cells. Such cells support the tumor microenvironment (TME) through reciprocal communications, which together, initiate and sustain hallmarks of cancer. In addition, recent studies have indicated functional phenotypic interconversion properties of tumor cells, also known as plasticity, which further contribute to the cellular complexity of tumors and their behaviors. For example, the ability of tumors to survive therapeutic targeting and to promote tumor progression and metastasis is thought to be conferred by a combination of phenotypic, cellular and functional diversity of different cell types. The molecular underpinnings of this diversity are not restricted to genetic factors alone but also depend on non-genetic determinants, largely related to epigenetic modifications and metabolic signals emanating from the TME and the tumor cells themselves.

The Kim lab has developed sophisticated tumor models that allow conditional and reversible expression of cancer-inducing oncogenes and simultaneous visible exploitation of cell fates via genetic fluorescent lineage tracing in vivo. Importantly, these models enable to isolate previously healthy cancer cells of origin such as bronchioalveolar lung stem cells (BASCs), the transformed descendant and surrounding cells within the healthy tissue in which tumors develop as well as the stroma of an established tumor (immune, mesenchymal and endothelial). Essentially, this approach enables to isolate and manipulate defined cell types undergoing transitions from the organism, in purity and at any given time. Therefore, with these unique models, the molecular dynamics that instruct cellular transformation and how surrounding stromal cells of the microenvironment support tumor cell behaviors can be determined at very high resolutions across spatio-temporal scales. Using such animal models of lung tumorigenesis, the Kim lab will perform temporally resolved systems-level integrative analyses on purified populations of the lung as they transform and when lung tumors are established. This approach includes highly resolved spatial transcriptomics, a novel technology that enables to specifically map and allocate gene expression changes to exactly where and in which cell types they are occurring down to the single-cell level. In collaboration with the Savai lab, this data will intricately connect to high-end image analyses that will allow to determine the contributions and response of the stroma towards lung tumor initiation and maintenance. The Kim lab will harness profound expertise in functional genomics and test functions of potential (epi-)genetic/metabolic effectors of cellular transformation using arrayed, genome-wide libraries on primary tumor cells purified from the genetically engineered mice.

The lab for Spatio-Temporal Dynamics of Tumorigenesis focuses on the following major objectives:

1) Delineation of stromal and epi-metabolic determinants of acquired plasticity in tumor initiation and maintenance. This includes dissection of the

  • (i) genetics  of the previously healthy cancer cell of origin and the transformed descendant,
  • (ii) microenvironment (e.g. stroma and/or regenerating and non-regenerating conditions),
  • (iii) epigenetics of both.

2) Targeting the epi-metabolome and inter-tumor heterogeneity in functional genomic screens.

3) Investigating reversible mesenchymal to epithelial transitions as a function of acquired plasticity in tumor organoids.


Figure 1: Overview of the research topics addressed in the Kim lab
(TME: Tumor Microenvironment, FACS: Fluorescence Activated Cell Sorting)


Most important publications (recent)

Chen, Y., Lüttmann, F.F., Schoger, E., Schöler, H.R., Zelarayán, L.C., Kim, K.P., Haigh, J.J., Kim, J*., and Braun, T*, Reversible reprogramming of cardiomyocytes to a fetal state drives adult heart regeneration in mice.
Science (2021, accepted), corresponding author

Kim, KP., Li, C., Bunina, D., Jeong, H.W., Ghelman, J., Kwak, T.H., Yoon, J., Shin, B., Park, H., Han, D.W., Zaugg, J.B., Kim, J.,  Kuhlmann, T., Adams, R.H., Noh, K.M., Goldman, S.A., Schöler, H.R. Donor-cell Memory Confers Metastable State of Directly Converted Cells
Cell Stem Cell, 2021

Sreenivasan, K., Ianni, A., Kunne, C., Strilic, B., Gunther, S., Perdiguero, E., Kruger, M., Spuler, S., Offermanns, S., Gomez-Del Arco, P., Redondo, J. M., Munoz-Canoves, P., Kim, J*., Braun, T*., Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.
Cell Reports, 2020, corresponding author

Kim, J., Braun, T., Keeping Fibrotic Responses in Contractile Tissues at Bay: The Plot t(Hic1)ens.
Cell Stem Cell, 2020

Kim, KP., Choi, J., Yoon, J., Bruder, J., Shin, B., Kim, J., Arauzo-Bravo, M. J., Han, D., Wu, G., Han, D. W., Kim, J., Cramer, P., Schöler, H. R., Permissive epigenomic states endow reprogramming competence to a broad range of transcriptional regulators.
Nature Chemical Biology, 2020

Preussner, J., Zhong, J., Looso, M., Braun, T., Kim, J., Connect-four: genomic analyses of regenerating stem cells identifies zygotic Dux factors as tumor initiators.
Molecular and Cellular Oncology, 2019, corresponding author

 Weber, J., de la Rosa, J., Grove, C. S., Schick, M., Rad, L., Baranov, O., Strong, A., Pfaus, A., Friedrich, M. J., Engleitner, T., Lersch, R., Ollinger, R., Grau, M., Menendez, I. G., Martella, M., Kohlhofer, U., Banerjee, R., Turchaninova, M. A., Scherger, A., Hoffman, G. J., Hess, J., Kuhn, L. B., Ammon, T., Kim, J., Schneider, G., Unger, K., Zimber-Strobl, U., Heikenwalder, M., Schmidt-Supprian, M., Yang, F., Saur, D., Liu, P., Steiger, K., Chudakov, D. M., Lenz, G., Quintanilla-Martinez, L., Keller, U., Vassiliou, G. S., Cadinanos, J., Bradley, A.,Rad, R., PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.
Nature Communications, 2019

Preussner, J., Zhong, J., Sreenivasan, K., Gunther, S., Engleitner, T., Kunne, C., Glatzel, M., Rad, R., Looso, M., Braun, T., Kim, J, Oncogenic Amplification of Zygotic Dux Factors in Regenerating p53-Deficient Muscle Stem Cells Defines a Molecular Cancer Subtype.
Cell Stem Cell, 2018, corresponding author