Diana Toivola

Diana Toivola

Associate Professor Cell Biology

+358 50 500 7732


ORCID ID: 0000-0001-7165-9839

Description of Research

Research in the intestinal disease unit located at Åbo Akademi University is focused on the roles and regulation of molecular pathways in the health and disease of gastrointestinal epithelia of the colon and the endocrine pancreas, with focus on keratin intermediate filaments. Keratins are cytoskeletal dynamic structures important in protection from cellular stress. Keratin mutations predispose humans to diseases and the keratin (K)8 knockout mouse obtains an early IBD/ulcerative colitis-phenotype. Our aims are to understand how keratins help protect simple type epithelia on a molecular level, in particular in gastrointestinal organs with focus on intestine and the endocrine pancreas. Using keratin knockout mice, mice expressing keratin mutations, experimental models of colitis, colorectal cancer, diabetes, and cell systems including colon organoid 3D cultures, we study the role of keratins in e.g., mechanical stress, proliferation and differentiation, protein targeting, cancer, regeneration, and diabetes. We also aim to develop imaging modalities to detect IBD and colon cancer in mice in vivo. Webpage for the Epithelial biology laboratory at Åbo Akademi University: www.toivola-lab.org

Representative Publications

Stenvall C-GA, Tayyab M, Grönroos TJ, Ilomäki MA, Viiri K, Ridge KM, Polari L, Toivola DM. Targeted deletion of keratin 8 in intestinal epithelial cells disrupts tissue integrity and predisposes to tumorigenesis in the colon. Cell Mol Life Sci 2021 Dec 24;79(1):10.

Polari L, Alam CM, Nyström JH, Heikkilä T, Tayyab M, Baghestani S, Toivola DM. Keratin intermediate filaments in the colon: guardians of epithelial homeostasis. Int J Biochem Cell Biol. 2020 Dec;129:105878.

Lähdeniemi IAK, Misiorek JO, Antila CJM, Landor SK, Stenvall CA, Fortelius LE, Bergström LK, Sahlgren C, Toivola DM. Keratins regulate colonic epithelial cell differentiation through the Notch1 signalling pathway. Cell Death Differ. 2017 Jun;24(6):984-996.

Helenius TO, Antman CA, Asghar MN, Nyström JH, Toivola DM. Keratins Are Altered in Intestinal Disease-Related Stress Responses. Cells. 2016 Sep 10;5(3).

Misiorek JO, Lähdeniemi IAK, Nyström JH, Paramonov VM, Gullmets JA, Saarento H, Rivero-Müller A, Husøy T, Taimen P, Toivola DM. Keratin 8-deletion induced colitis predisposes to murine colorectal cancer enforced by the inflammasome and IL-22 pathway. Carcinogenesis. 2016 Aug;37(8):777-786.

Asghar MN, Priyamvada S, Nyström JH, Anbazhagan AN, Dudeja PK, Toivola DM. Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon. Am J Physiol Gastrointest Liver Physiol. 2016 Jun 1;310(11):G1147-54. doi: 10.1152/ajpgi.00354.2015.

Desai D, Prabhakar N, Mamaeva V, Karaman DS, Lähdeniemi IAK, Sahlgren C,  Rosenholm J, Toivola DM. Targeted Modulation of Cell Differentiation in Distinct Regions of the Gastrointestinal Tract via Oral Administration of Differently PEI-PEG Functionalized Mesoporous Silica Nanoparticles. Int. J. Nanomedicine, in press, November 2015.

Helenius TO, Misiorek JO, Nyström JH, Fortelius LE, Habtezion A, Liao J, Asghar MN, Zhang H, Azhar S, Omary MB, Toivola DM. Keratin 8 absence downregulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism. Mol Biol Cell, 26:2298-2310, 2015

Asghar MN, Silvander JS, Helenius TO, Lähdeniemi IA, Alam C, Fortelius LE, Holmsten RO, Toivola DM. The amount of keratin matters in stress protection of the colonic epithelium. PLoS One 10(5):e0127436, 2015

Asghar MN, Emani R, Alam C, Helenius TO, Grönroos TJ, Sareila O, Din MU, Holmdahl R, Hänninen A, Toivola DM. In vivo imaging of reactive oxygen and nitrogen species in murine colitis. Inflamm. Bowel Dis 20:1435-1447, 2014

Alam CM, Silvander JS, Daniel EN, Tao GZ, Kvarnström SM, Alam P, Omary MB, Hänninen A,Toivola DM. Keratin 8 modulates β-cell stress responses and normoglycaemia. J. Cell Sci. 126:5635-5644, 2013.

Habtezion A, Toivola DM, Asghar MN, Kronmal GS, Brooks JD, Butcher EC, Omary MB. Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon. Proc Natl Acad Sci USA, 108:1445-1450, 2011.

Toivola DM, Habtezion A, Strnad P, Omary MB. Intermediate filaments take the heat as stress proteins. Trends Cell Biol, 20:79-91, 2010.

Ku NO, Toivola DM, Strnad P, Omary MB. Cytoskeletal keratin glycosylation protects epithelial tissue from injury.Nat Cell Biol. 12:876-885, 2010.

Habtezion A, Toivola DM, Butcher EC, Omary MB. Keratin-8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment. J Cell Sci, 118:1971-1980, 2005.

Toivola DM, Krishnan S, Binder HB, Singh S, Omary MB. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol, 164:911-921, 2004.

Toivola DM, Tao GZ, Habtezion A, Liao J, Omary MB. Cellular integrity plus: organelle-related and protein-targeting functions of intermediate filaments. Trends Cell Biol, 15:608-617, 2005.