Karl Tryggvason



Contact: 66013127

Dr. Tryggvason is Professor at Duke-NUS Medical School, Singapore, Adjunct Professor at Duke University, North Carolina, and Emeritus Professor at the Karolinska Institute in Stockholm. His research concerns the molecular composition, biology and diseases of basement membranes (BM), a special compartment of the extracellular matrix. His group has cloned almost all human BM proteins and clarified genetic causes of many BM-associated diseases, such as Alport and congenital nephrotic syndromes, junctional epidermolysis bullosa and congenital muscular dystrophy. He has studied matrix metalloproteinases, discovered MMP-2 and determined its crystal structure of. His group has produced most laminins as recombinant human proteins and recently the group has shown that different laminin isoforms influence stem cell growth and differentiation. His group has developed fully human and chemically defined laminin-based methods for generation of stem cell derived cardiomyocytes, retina RPE and photoreceptors, keratinocytes and pancreatic islet cells. Currently, the group works on the development stem cell derived cells for regenerative medicine.

Tryggvason has published over 400 research articles. He is a member of the Finnish Academy of Sciences and the Swedish Royal Academy of Sciences, and has served for 18 years as a member of the Nobel Assembly and Committee for Physiology or Medicine at the Karolinska Institute. He has received several international awards, and he is co-founder of BioLamina AB, Stockholm, that produces laminins for cell biology and cell therapy purposes.

My research concerns broad studies on the protein components and diseases of basement membranes. My group has cloned genes and cDNAs for most human basement membrane components, type IV collagens, laminins and perlecan. The discovery of a novel, highly glomerular basement membrane specific type IV collagen α5 chain in 1990, led to the elucidation of the first inherited basement membrane and glomerular disease, Alport syndrome. This was followed-up by identifying laminin gene mutants causing junctional epidermolysis bullosa and congenital muscular dystrophy. The positional cloning of the congenital nephrotic syndrome gene encoding the novel protein nephrin in 1998 was important for nephrology, as it opened up for a new understanding of the molecular structure and crucial role of the podocyte slit diaphragm in the renal filtration system.

I currently apply a systems biology approach to diseases of the renal filter including identification of novel glomerular proteins, molecular signatures of disease processes and identification of susceptibility genes for diabetic nephropathy. Two other main research themes involve specific BM proteins called laminins and their roles in stem cell biology and bacteria-binding scavenger receptors with collagenous structures and their potential for sepsis treatment.

Selected Publications

ORCID NO: 0000-0003-1292-9266

1. Rodin, S, Domogatskaya A, Ström S, Hansson EM, Chien KR, Inzunza J, Hovatta O, Tryggvason K. Long-term self-renewal of human embryonic stem cells on human recombinant laminin-511 in xeno-free and feeder-free environment.Nature Biotechnol. 28, 611-615, 2010.  

2. Rodin S, Antonsson L, Niaudet C, Simonson OE, Salmela E, Hansson EM, Domogatskaya A, Xiao Z, Damdimopoulou P, Sheikhi M, Inzunza J, Nilsson A-S, Baker Duncan, Kuiper R, Sun Y, Blennow E, Nordenskjöld1 M, Grinnemo K-H, Kere J, Betsholtz C, Hovatta O, Tryggvason. Clonal derivation, clonal survival and long-term self-renewal of human embryonic stem cells on laminin-521/E-cadherin matrix in chemically defined and xeno-free environment. Nature Communications 5, Jan 27, 2014.  

3. Tjin MS, Chua AWC, Moreno-Moral A, Chong LY, Tan PY, Harmston NP, Petretto E, Tan BK, Tryggvason K. Biologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture. Nature Commun. 2018 Oct 30;9(1):4432. doi: 10.1038/s41467-018-06934-3.  

4. Yap L, Wang J-W, Moreno-Moral A, Chong L-Y, Sun Y, Harmston N, Wang X, Chong SY, Öhman MK, Wei H, Bunte R, Gosh S, Cook S, Hovatta O, Klejn DPV, Petretto E, Tryggvason K. In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors. Cell Reports. 26, 1-15, March 19, 2019 

5. Tay HG, Andre H, Guo J, Ren X, Tan WS, Moreno-Moral A, Bartuma H, Sigmundsson K, Cai Z, Holmgren A, Kvanta A, Petretto, and Tryggvason K. Retina-specific Laminin 523 Drives Differentiation of Pluripotent Human Stem Cells to Photoreceptors That Exhibit Synaptic Connectivity in the Retina. Nat Commun. Under review, 2020.