Börje Haraldsson

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Börje Haraldsson
Born (1957-10-14) October 14, 1957 (age 66)
Borås, Sweden
NationalitySwedish
Other namesBörje Haraldsson
Boerje Haraldsson
Borje Haraldsson
Alma materUniversity of Gothenburg
Occupation(s)Physician-scientist, and academic
Known forwork on kidney disease
SpouseKarin Haraldsson
Scientific career
InstitutionsOncorena AB
University of Gothenburg

Börje Haraldsson is a Swedish Physician-scientist known for his work on kidney disease. He is the Chief Executive Officer at Oncorena AB, and a Professor of Physiology in Sahlgrenska Academy at the University of Gothenburg.[1] He is also a Fellow of the American Society of Transplantation (FAST), and the American Society of Nephrology (FASN).[2]

Early life and education[edit]

Haraldsson was born on October 14, 1957, in Borås, Sweden. After completing his early education in a high school at Bäckängsgymnasiet, he started medical school at the University of Gothenburg in 1976. There he performed his graduate work in physiology to receive his M.D. in 1982 and Ph.D in 1986, under the supervision of Bengt Rippe and Björn Folkow. His dissertation was titled "Physiological studies of macromolecular transport across capillary walls".[3]

Career[edit]

During his doctoral studies, Haraldsson began his clinical career as a part-time physician in emergency rooms in Borås, Vänersborg, Bäckefors, and Lysekil. He completed his internship at Mölndals hospital, Sweden in 1989, and was subsequently appointed by Sahlgrenska university hospital as Resident Physician. Afterward, he served there as an attending physician till 2000, and as senior consultant till 2014.[4]

Haraldsson was appointed as an associate professor (docent) of Physiology at Gothenburg University till 2000, and as a Professor and Chair of Nephrology till 2015. During this time period, he also held concurrent appointments as Researcher in integrative physiology, as Department Head, as Director of the university board, and as Vice Dean for the Sahlgrenska academy at the University of Gothenburg. Moreover, he chaired several Swedish Research Council’s expert panels, and served as scientific secretary of the Gothenburg Medical Association. From 2011 till 2014, he was a visiting professor of medicine at Mount Sinai School of medicine in New York.[4]

In 2015, Haraldsson resigned his clinical professorship to join Novartis in Switzerland. As he returned to Sweden in 2022, he rejoined the University of Gothenburg as Professor of Physiology.[5]

In 2014, Haraldsson held appointment as an Executive Director at Novartis Institute of Biomedical research (NIBR). After working there as a translational medicine expert in the ATI department for 3 years, he became Global Program Head in immunology, hepatology and dermatology (IHD) in 2018. In 2022, he left Novartis to become CSO, and four months later CEO, at Oncorena AB.[5]

Haraldsson is the Founder of three consultancy firms: Hand i Hand, Soinial AB, and Creorena AB.

Research[edit]

Haraldsson has focused his research on kidney disease, with particular attention on the properties of the glomerular barrier crucial for whole-body homeostasis and survival. His clinical expertise includes hypertension, hemodialysis, clinical nephrology, and chronic kidney failure.[6] Currently, Haraldsson has been working on the development of a new drug that could cure widespread kidney cancer.[5]

Novel techniques to assess permeability in different organs[edit]

Haraldsson introduced several models and techniques to explore the permeability in different organs. Together with Bengt Rippe, he developed the two-pore model for solute exchange,[7][8] and later the three-pore model for fluid and solute exchange across capillary walls.[9] They provided new insights regarding fenestrated capillaries of the pancreatic, and salivary glands which were considered to ‘leak’ proteins. They demonstrated that these capillaries had similar permselectivity as continuous capillaries.[10]

Haraldsson is also the one to discover the role of orosomucoid in terms of maintenance of normal capillary permselectivity.[11] He regarded the endothelial cell surface layer (ESL) to be the key contributor in the context of the glomerular barrier.[12] In a study conducted in 1993, he discussed the application of plasma glycoprotein orosomucoid in regulating the dynamic properties of the glomerular capillary wall by reducing the permeability towards macromolecules.[13] He developed a computer model for individualized therapy of patients with PD,[14] and regarded total pore area over diffusion distance (A(0)/Deltax) to be the significant parameter to describe exchange across the peritoneal membrane.[15]

Understanding of the glomerular barrier and its components[edit]

Haraldsson’s research group published a series of papers focused on the understanding of the glomerular barrier, its properties, and the role of its individual components.[16][17] In a paper published in 1992, he highlighted the role of orosomucoid in terms of maintenance of normal capillary permeability in skeletal muscle and mesentery. The research group also demonstrated that serum proteins other than albumin and orosomucoid are less important for the maintenance of normal capillary permeability.[18] In 2003, he and Jeansson conducted the first functional study of glomerular size and charge selectivity in mice to explore the controversial issue of glomerular permselectivity in animals exposed to glucosaminoglycan-degrading enzymes, hyaluronidase, and heparinase.[19] It was found out that polysaccharide-rich structures, such as the endothelial cell coat are key components in the glomerular barrier.[20]

Building on work by William Deen, Haraldsson developed the first unified heterogenous charged fiber model, while incorporating the effects of solute size and charge.[21] He along with co-workers, also demonstrated how the structure of the ESL can be affected by enzymes, ischemia-reperfusion injury, or ionic strength, causing proteinuria. He studied the interaction between podocytes, the endothelial cells, and their ESL, and presented conditions with disturbed communication causing proteinuria.[21] In 2014, together with colleagues in New York, he confirmed the reciprocal crosstalk between podocytes and endothelial cells in a coculture system, and further highlighted that segmental glomerulosclerosis develops as a result of podocyte-endothelial crosstalk mediated by EDN1/EDNRA-dependent mitochondrial dysfunction.[22]

While focusing his studies on orellanine,[23] Haraldsson’s group introduced HPLC-ESI-MS/MS method which has the ability to monitor orellanine at low concentrations within the therapeutic interval in blood serum.[24] Later on, the research group provided long-term clinical outcomes for patients poisoned by the fungal nephrotoxin orellanine.[25] Their studies also suggested the usage of orellanine in terms of eliminating human renal cancer carcinomas with its highly organ-specific cytotoxic properties.[26]

Awards and honors[edit]

  • 1999 - High Pedagogical Award, University of Gothenburg
  • 2009 - Recipient of "Guldtackan" for contributions to the Medical Students[citation needed]

Selected publications[edit]

  • Nashan, B., Tedesco, H., Van den Hoogen, M. W., Berger, S. P., Cibrik, D., Mulgaonkar, S., ... & Witzke, O. (2018). CD40 inhibition with CFZ533-a new, fully human, non-depleting, Fc silent mAB-improves renal allograft function while demonstrating comparable efficacy vs. tacrolimus in de-novo CNI-free kidney transplant recipients. Transplantation, 102, S366.
  • Nystrom, J., Khramova, A., Haraldsson, B., & Ebefors, K. (2019). SAT-125 Proteoglycans are glomerular endothelial glycocalyx components playing a major role in permselectivity and prevention of proteinuria. Kidney International Reports, 4(7), S57.
  • Webb, N., Haraldsson, B., Schubart, A., Milojevic, J., End, P., Holbro, T., & Junge, G. (2020). MO042 LNP023: A NOVEL ORAL COMPLEMENT ALTERNATIVE PATHWAY FACTOR B INHIBITOR FOR THE TREATMENT OF GLOMERULAR DISEASE. Nephrology Dialysis Transplantation, 35(Supplement_3), gfaa140-MO042.
  • Ballermann, B. J., Nystrom, J., & Haraldsson, B. (2021). The glomerular endothelium restricts albumin filtration. Frontiers in Medicine, 2402.
  • Khramova, A., Boi, R., Fridén, V., Granqvist, A. B., Nilsson, U., Tenstad, O., ... & Nyström, J. (2021). Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease. Scientific reports, 11(1), 1-12.

References[edit]

  1. ^ "Börje Haraldsson - University of Gothenburg".
  2. ^ "ASN Congratulates the FASN Inductees".
  3. ^ Haraldsson, B. (1986). "Physiological studies of macromolecular transport across capillary walls. Studies on continuous capillaries in rat skeletal muscle". Acta Physiologica Scandinavica. Supplementum. 553: 1–40. PMID 3466511.
  4. ^ a b "Oncorena appoints Chief Scientific Officer". 5 February 2022.
  5. ^ a b c "Njurprofessorn Börje Haraldsson tillbaka i Göteborg".
  6. ^ "BBB seminar: Börje Haraldsson".
  7. ^ Rippe, B.; Haraldsson, B. (1987). "Fluid and protein fluxes across small and large pores in the microvasculature. Application of two-pore equations". Acta Physiologica Scandinavica. 131 (3): 411–428. doi:10.1111/j.1748-1716.1987.tb08257.x. PMID 3321914.
  8. ^ Rippe, B.; Haraldsson, B. (1994). "Transport of macromolecules across microvascular walls: the two-pore theory". Physiological Reviews. 74 (1): 163–219. doi:10.1152/physrev.1994.74.1.163. PMID 8295933.
  9. ^ Rippe, B.; Stelin, G.; Haraldsson, B. (1991). "Computer simulations of peritoneal fluid transport in CAPD". Kidney International. 40 (2): 315–325. doi:10.1038/ki.1991.216. PMID 1942781.
  10. ^ Moxham, B.J.; Shore, R.C.; Berkovitz, B.K.B. (1985). "Fenestrated capillaries in the connective tissues of the periodontal ligament". Microvascular Research. 30 (1): 116–124. doi:10.1016/0026-2862(85)90043-3. PMID 4021834.
  11. ^ Haraldsson, B.; Rippe, B. (1987). "Orosomucoid as one of the serum components contributing to normal capillary permselectivity in rat skeletal muscle". Acta Physiologica Scandinavica. 129 (1): 127–135. doi:10.1111/j.1748-1716.1987.tb08047.x. PMID 3565039.
  12. ^ Fridén, V.; Oveland, E.; Tenstad, O.; Ebefors, K.; Nyström, J.; Nilsson, U. A.; Haraldsson, B. (2011). "The glomerular endothelial cell coat is essential for glomerular filtration". Kidney International. 79 (12): 1322–1330. doi:10.1038/ki.2011.58. PMID 21412215.
  13. ^ Johnsson, E.; Haraldsson, B. (1993). "Addition of purified orosomucoid preserves the glomerular permeability for albumin in isolated perfused rat kidneys". Acta Physiologica Scandinavica. 147 (1): 1–8. doi:10.1111/j.1748-1716.1993.tb09466.x. PMID 8452035.
  14. ^ Haraldsson, B. (1995). "Assessing the peritoneal dialysis capacities of individual patients". Kidney International. 47 (4): 1187–1198. doi:10.1038/ki.1995.169. PMID 7783418.
  15. ^ Fischbach, M.; Haraldsson, B. (2001). "Dynamic changes of the total pore area available for peritoneal exchange in children". Journal of the American Society of Nephrology. 12 (7): 1524–1529. doi:10.1681/ASN.V1271524. PMID 11423582.
  16. ^ Haraldsson, B.; Ekholm, C.; Rippe, B. (1983). "Importance of molecular charge for the passage of endogenous macromolecules across continuous capillary walls, studied by serum clearance of lactate dehydrogenase (LDH) isoenzymes". Acta Physiologica Scandinavica. 117 (1): 123–130. doi:10.1111/j.1748-1716.1983.tb07186.x. PMID 6858700.
  17. ^ Haraldsson, B.; Rippe, B. (1985). "Serum factors other than albumin are needed for the maintenance of normal capillary permselectivity in rat hindlimb muscle". Acta Physiologica Scandinavica. 123 (4): 427–436. doi:10.1111/j.1748-1716.1985.tb07609.x. PMID 3993401.
  18. ^ "Glomerular permselectivity is dependent on adequate serum concentrations of orosomucoid".
  19. ^ Jeansson, M.; Haraldsson, B. (2003). "Glomerular size and charge selectivity in the mouse after exposure to glucosaminoglycan-degrading enzymes". Journal of the American Society of Nephrology. 14 (7): 1756–1765. doi:10.1097/01.asn.0000072742.02714.6e. PMID 12819235. S2CID 7501308.
  20. ^ Ciarimboli, G.; Hjalmarsson, C.; Bökenkamp, A.; Schurek, H. J.; Haraldsson, B. (2003). "Dynamic alterations of glomerular charge density in fixed rat kidneys suggest involvement of endothelial cell coat". American Journal of Physiology. Renal Physiology. 285 (4): F722-30. doi:10.1152/ajprenal.00227.2001. PMID 12812917. S2CID 23427869.
  21. ^ a b Andersson, M.; Nilsson, U.; Hjalmarsson, C.; Haraldsson, B.; Nyström, J. S. (2007). "Mild renal ischemia-reperfusion reduces charge and size selectivity of the glomerular barrier". American Journal of Physiology. Renal Physiology. 292 (6): F1802-9. doi:10.1152/ajprenal.00152.2006. PMID 17376766.
  22. ^ Daehn, I.; Casalena, G.; Zhang, T.; Shi, S.; Fenninger, F.; Barasch, N.; Yu, L.; d'Agati, V.; Schlondorff, D.; Kriz, W.; Haraldsson, B.; Bottinger, E. P. (2014). "Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis". The Journal of Clinical Investigation. 124 (4): 1608–1621. doi:10.1172/JCI71195. PMC 3973074. PMID 24590287.
  23. ^ Nilsson, U. A.; Nyström, J.; Buvall, L.; Ebefors, K.; Björnson-Granqvist, A.; Holmdahl, J.; Haraldsson, B. (2008). "The fungal nephrotoxin orellanine simultaneously increases oxidative stress and down-regulates cellular defenses". Free Radical Biology & Medicine. 44 (8): 1562–1569. doi:10.1016/j.freeradbiomed.2008.01.017. PMID 18279679.
  24. ^ Herrmann, Anders; Hedman, Heidi; Rosén, Johan; Jansson, Daniel; Haraldsson, Börje; Hellenäs, Karl-Erik (2012). "Analysis of the mushroom nephrotoxin orellanine and its glucosides". Journal of Natural Products. 75 (10): 1690–1696. doi:10.1021/np300135k. PMID 23046414.
  25. ^ Hedman, Heidi; Holmdahl, Johan; Mölne, Johan; Ebefors, Kerstin; Haraldsson, Börje; Nyström, Jenny (2017). "Long-term clinical outcome for patients poisoned by the fungal nephrotoxin orellanine". BMC Nephrology. 18 (1): 121. doi:10.1186/s12882-017-0533-6. PMC 5379567. PMID 28372584.
  26. ^ Buvall, L.; Hedman, H.; Khramova, A.; Najar, D.; Bergwall, L.; Ebefors, K.; Sihlbom, C.; Lundstam, S.; Herrmann, A.; Wallentin, H.; Roos, E.; Nilsson, U. A.; Johansson, M.; Törnell, J.; Haraldsson, B.; Nyström, J. (2017). "Orellanine specifically targets renal clear cell carcinoma". Oncotarget. 8 (53): 91085–91098. doi:10.18632/oncotarget.19555. PMC 5710908. PMID 29207627.
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