Group Martin Johansson

Research summary

I have recently been recruited from Lund University/Malmö University Hospital and our research is a continuation of the projects that were initiated there. We primarily study two important aspects of human kidney disease. The projects are distinct, but also interconnected.

Research focus - renal cell carcinoma

The first area of investigation concerns renal cell carcinoma (RCC). This form of cancer has many unique features. From a therapeutic standpoint, classical treatments as cytostatics or radiation have only marginal effects on RCC progression. Surgery therefore remains the only curative treatment despite some improvements in survival following the introduction of anti-angiogenesis protocols by RTK-inhibition and immune-checkpoint inhibition.

Furthermore, from a tumour biological perspective, all forms of kidney cancer are more or less diseases of aberrant cellular metabolism. Therefore we currently investigate the metabolism of the most common and malignant form of kidney cancer, clear cell renal cell carcinoma (CCRCC).

The absolute majority of these cancers are initiated by biallelic loss of function of the VHL-gene. This induces a so called hypoxia response via the hypoxia inducible transcription factors HIF-1 and HIF-2. This results in major changes in cellular metabolism and a very distinct morphology of these cancers. The cells are filled with lipid and glycogen in order to accumulate energy and the cancer tissue displays an unique degree of vascularization. Our goal is to investigate this pseudohypoxic cellular metabolism in detail in order to identify novel therapeutic targets.

We have previously shown that CCRCC cells lack functional mitochondria (5). This renders the cancer cells highly dependent upon aerobic glycolysis turning glucose into pyruvic acid and then lactate which makes them uniquely vulnerable to blockade of this pathway.

We are also interested in the pronounced tumour heterogeneity associated with CCRCC. Along these lines we are studying CCRCC with eosinophilic histology. A third area of research addresses the mechanisms by which the cancer cells accumulate the lipids leading to their characteristic phenotype.

Finally, papillary renal cell carcinoma (PRCC) is the second most common renal malignancy. For this form of cancer, no treatments are available. We investigate how PRCC cells interact with their immune cell environment and we also aim to develop novel treatment strategies for this cancer.

Research focus - kidney regeneration

Our other main focus centers on kidney regeneration. Human kidney disease is rapidly increasing globally, but kidney injury develops only if the regenerative capacity of the kidney is overrun. Despite the importance of the regenerative mechanisms of the kidney, the cellular basis for kidney regeneration is not settled.

The traditional view, that stochastically surviving kidney cells repopulate the tubules after injury has been challenged by the concept of a resident stem or progenitor cell pool localized to the kidney. We have identified a tubular scattered cell population in the human kidney, of importance for kidney regeneration (6, 9). We are currently studying these cells using multiple approaches.

Research tools and resources

In cooperation with the departments of urology in Gothenburg and Malmö, we have an ongoing biobanking of RCC and normal kidney tissue. The basis for our research is primary culture of human RCC cells and kidney cells.

We have established projects with professor Thomas Laurell at Lund Technical University and professor David Gardner at University of Nottingham. With the former, we are producing a microfludic chip to study kidney structure and signaling and professor Gardner will aid us in establishing a porcine kidney injury model.

Current group members

Martin Johansson, Professor, Chief physician and group leader at Sahlgrenska Center for Cancer Research.
Yvonne Arvidsson, PhD, Associate Professor
Rasmus Jakobsson, PhD Student, resident in Urology
Sofia Johansson, PhD Student

Selected publications

1. Localization and regulation of pIgR in healthy and diseased human kidney.
   Krawczyk, K. M., Nilsson, H., Nyström, J., Lindgren, D., Leandersson K. Swärd K and Johansson M. E. American Journal of Pathology. Oct;189 (10):1933-1944. 2019.

2. Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.
   Lindgren D, Eriksson P, Krawczyk K, Nilsson H, Hansson J, Veerla S, Sjölund J, Höglund M, Johansson ME, Axelson H.  Cell Reports. Aug 8;20(6):1476-1489. 2017.

3. Orellanine specifically targets renal clear cell carcinoma.
   Hedman H, Buvall L, Najar D, Lundstam S, Herrmann A, Wallentin H, Roos E, Nilsson U.A, Johansson M, Nyström J & Haraldsson B. Oncotarget. Jul 25;8(53):91085-91098. 2017.

4. Papillary renal cell carcinoma-derived chemerin, IL-8 and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages.
   Krawczyk K, Nilsson H, Allaoui R , Lindgren D, Arvidsson M, Leandersson K and Johansson ME. Laboratory Investigation, Nov;97(11):1296-1305. 2017.

5. Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.
   Nilsson H, Lindgren D, Mandahl Forsberg A, Hallin U, Axelson H, Mulder H and Johansson ME. Cell Death and Disease. Jan 8:6. 2015.

6. Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney.
   Hansson J, Hultenby K, Lindgren D, Cramnert C, Axelson H and Johansson ME. Human Pathology. Feb;45(2):382-93. 2014.

7. Increased Expression of the Very Low-Density Lipoprotein Receptor Mediates Lipid Accumulation in Clear-Cell Renal Cell Carcinoma.
   Perman-Sundelin J, Ståhlman M, Lundqvist A, Levin M, Parini P, Johansson ME*, Borén J*  PLoS One. 7(11). 2012.

8. Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
   Boström AK, Möller C, Nilsson E, Elfving P, Axelson H and Johansson ME. Human Pathology. May;43(5):708-19. 2012.

9. Isolation and characterization of progenitor-like cells from human renal proximal tubules.
   Lindgren D, Boström A-K, Nilsson K, Hansson J, Sjölund J, Möller C, Jirström K, Nilsson E, Landberg G, Axelson H, and Johansson ME. American Journal of Pathology. Feb;178(2):828-37. 2011.

More group Martin Johansson publications on PubMed