JAKOB WIKSTRÖM TEAM

Mitochondria and endoplasmic reticulum in wound healing and rare skin conditions

About

Dr Jakob Wikström has completed MD PhD as well as postdoctoral fellowship, and has recently established his own independent research team. His previous research has been focused on the role of mitochondria and endoplasmic reticulum in brown adipose tissue and pancreatic beta cells. Dr Wikström´s clinical specialty is dermato-venereology and the research is therefore directed on skin physiology and diseases.

Chronic leg ulcers cause great suffering in the elderly and consume 2 % of the health budget; yet the wound healing process is incompletely understood and today´s treatments are often inadequate. Mitochondria produce 90 % of the cell’s ATP, which is essential for most biological reactions including those involved in wound healing. To achieve this, mitochondria consume 90 % of the body´s oxygen. As wound healing has high energy requirements and the hypoxic nature of most wounds we are currently studying the role of mitochondria in the healing of chronic leg ulcers.

We also study the rare genetic conditions Darier´s disease and Hailey-Hailey´s disease, which are caused by disrupted calcium homeostasis in the endoplasmic reticulum and Golgi apparatus, respectively. Our aim is to gain better understanding of these diseases and to conduct a translational study in which we aim to develop improved therapies. Please contact Dr Jakob Wikström if you are a patient or healthy volunteer and would like to take part in this cutting edge research.

We are always looking for highly motivated scientists interested in joining our growing team.

 

Research funding

Svenska Sällskapet för Medicinsk Forskning

Vetenskapsrådet

Leo Fondet

Diabetesfonden

Olle Engqvists stiftelse

Hudfonden

Jeanssons stiftelse

STINT

Stiftelsen Lars Hiertas minne

Ostermanns stiftelse

EFSD

Tore Nilssons stiftelse

 

Information to study participants and patients

Here we want to inform on what diseases we conduct research and what study participants we are looking for. It is also important for us to continously communicate the study results under the headline “Latest news”.

Latest news

October 2017: We have published a study on novel mutations among Darier patients. We have not been able to correlate mutation type to disease severity which suggest that this disease vary considerably. https://www.ncbi.nlm.nih.gov/pubmed/29028823

 

Leg ulcers

We study chronic leg ulcers among the elderly with the long term purpose of developing better treatment methods. Currently we have two main research directions. Firstly we study how the power plants of the cells, the mitochondria, can affect wound healing. Mitochondria consume the majority of the body’s oxygen which we believe is extra important in wound healing. Secondly we study the role of how so called folding of the body’s building blocks, proteins, affect wound healing. In tissue regeneration new proteins are needed and many must be folded to specific structures in order to work properly.

We are always on the lookout for healthy volunteers who can agree to skin biopsies. We are particularly interested in participants over the age of 60. We are also looking for patients with chronic leg ulcers; especially venous ulcers, diabetes-/neuropathic ulcers and decubitus/pressure sores.

Please contact Dr Jakob Wikström for more information:

jakob.wikstrom@sll.se

073-9611019

 
 
 
 

Selected publications

Bachar-Wikstrom E, Curman P, Ahanian T, Leong IUS, Larsson H, Cederlöf M, Wikstrom JD. Darier disease is associated with heart failure: a cross-sectional case-control and population based study Scientific Reports 2020 Apr 23;10(1):6886. 

Benador IY, Veliova M, Mahdaviani K, Petcherski A, Wikstrom JD, Assali EA, Acín-Pérez R, Shum M, Oliveira MF, Cinti S, Sztalryd C, Barshop WD, Wohlschlegel JA, Corkey BE, Liesa M, Shirihai OS. Mitochondria Bound to Lipid Droplets Have Unique Bioenergetics, Composition, and Dynamics that Support Lipid Droplet Expansion. Cell Metab. 2018 Apr 3;27(4):869-885.e6.

Leong IUS, Stuckey A, Ahanian T, Cederlöf M, Wikstrom JD*. Novel mutations in Darier disease and association to self-reported disease severity. PLoS One. 2017 Oct 13;12(10):e0186356. *Corresponding author.

Li X, Li D, Wikstrom JD, Pivarcsi A, Sonkoly E, Ståhle M, Landén NX. MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing. Sci Rep. 2017 Aug 10;7(1):7797.

Riahi Y*, Wikstrom JD*, Bachar-Wikstrom E, Polin N, Zucker H, Lee MS, Quan W, Haataja L, Liu M, Arvan P, Cerasi E, Leibowitz G. Autophagy is a major regulator of beta cell insulin homeostasis. Diabetologia. 2016 Jul;59(7):1480-91. *Equal contribution.

Wikstrom JD, Mahdaviani K, Liesa M, Sereda SB, Si Y, Las G, Twig G, Petrovic N, Zingaretti C, Graham A, Cinti S, Corkey BE, Cannon B, Nedergaard J, Shirihai OS. Hormone-induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure. EMBO J. 2014 Mar 3;33(5):418-36.

Wikstrom JD, Israeli T, Bachar-Wikstrom E, Swisa A, Ariav Y, Waiss M, Kaganovich D, Dor Y, Cerasi E, Leibowitz G. AMPK regulates ER morphology and function in stressed pancreatic β-cells via phosphorylation of DRP1. Mol Endocrinol. 2013 Oct;27(10):1706-23.

Bachar-Wikstrom E, Wikstrom JD, Ariav Y, Tirosh B, Kaiser N, Cerasi E, Leibowitz G. Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes. 2013 Apr;62(4):1227-37.

Wikstrom JD, Sereda SB, Stiles L, Elorza A, Allister EM, Neilson A, Ferrick DA, Wheeler MB, Shirihai OS. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets. PLoS One. 2012;7(5):e33023.

Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B,Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010 Jan 22;140(2):280-93.

Molina AJ, Wikstrom JD, Stiles L, Las G, Mohamed H, Elorza A, Walzer G, Twig  G, Katz S, Corkey BE, Shirihai OS. Mitochondrial networking protects beta-cells from nutrient-induced apoptosis. Diabetes. 2009 Oct;58(10):2303-15.

Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 2008 Feb;14(2):144-53.

Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008 Jan 23;27(2):433-46.