The research focus of the Epigenetics of skin aging Group centers around cellular aging in normal and disease states, with a particular focus on the molecular and cellular pathogenesis of premature aging diseases such as Hutchinson- Gilford progeria syndrome (HGPS). This cutting edge research can inform both interventions for this fatal disorder and reveal further insights into normal aging. The team uses multidisciplinary approaches to investigate the molecular mechanisms underlying premature aging. They want to determine how alterations in the LMNA gene which encodes lamin A and C proteins that are critical components of the nuclear envelope that protects the genome integrity contribute to cellular aging. Moreover, by examining the processes underlying premature aging syndromes the team can determine if similar mechanisms trigger normal aging including age-related diseases, particularly skin, vascular and neurological disorders affecting the elderly population. Furthermore, the team aims to define, isolate and characterize skin stem cells to identify how aging might impact stem cell renewal and differentiation. This unique approach to the study of aging makes the laboratory the only one in Germany to examine the characteristics of aging from this angle.
Research into treatments for HGPS is the mission of the team. Previous studies indicate that proteostasis is altered in HGPS cells. Hence, studying the mechanisms by which protein breakdown regulates the processes of aging could be the key to identifying therapeutic interventions, which promote healthy cellular function and ameliorate age-related pathologies.
Budel L, Djabali K. Rapid isolation and expansion of skin-derived precursor cells from human primary fibroblast cultures. Biol Open. 2017 Nov 15;6(11):1745-1755.
Gabriel D, Shafry DD, Gordon LB, Djabali K. Intermittent treatment with farnesyltransferase inhibitor and sulforaphane improves cellular homeostasis in Hutchinson-Gilford progeria fibroblasts. Oncotarget. 2017 Jul 18;8(39):64809-64826.
Konstantinow A, Arnold A, Djabali K, Kempf W, Gutermuth J, Fischer T, Biedermann T. Therapy of ulcus cruris of venous and mixed venous arterial origin with autologous, adult, native progenitor cells from subcutaneous adipose tissue: a prospective clinical pilot study. J Eur Acad Dermatol Venereol. 2017 Dec;31(12):2104-2118.
Djabali K, Ring J. Mesenchymal stem cells may hold the secret to healing skin disease. J Eur Acad Dermatol Venereol. 2017 Mar;31(3):387.
Gabriel D, Gordon LB, Djabali K. Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype.
PLoS One. 2016 Dec 29;11(12):e0168988.
Eisch V, Lu X, Gabriel D, Djabali K. Progerin impairs chromosome maintenance by depleting CENP-F from metaphase kinetochores in Hutchinson-Gilford progeria fibroblasts. Oncotarget. 2016 Apr 26;7(17):24700-18.
Miyamoto MI, Djabali K, Gordon LB. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link? Glob Heart. 2014 Jun;9(2):211-8. doi: 10.1016/j.gheart.2014.04.001.
Gabriel D, Roedl D, Gordon LB, Djabali K. Sulforaphane enhances progerin clearance in Hutchinson-Gilford progeria fibroblasts. Aging Cell. 2015 Feb;14(1):78-91.
Blondel S, Jaskowiak AL, Egesipe AL, Le Corf A, Navarro C, Cordette V, Martinat C, Laabi Y, Djabali K, de Sandre-Giovannoli A, Levy N, Peschanski M, Nissan X. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome. Stem Cells Transl Med. 2014 Apr;3(4):510-9.
Wenzel V, Roedl D, Ring J, Djabali K. Naïve adult stem cells isolation from primary human fibroblast cultures. J Vis Exp. 2013 May 3;(75):e50185.
Wenzel V, Roedl D, Gabriel D, Gordon LB, Herlyn M, Schneider R, Ring J, Djabali K. Naïve adult stem cells from patients with Hutchinson-Gilford progeria syndrome express low levels of progerin in vivo. Biol Open. 2012 Jun 15;1(6):516-26.
Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging.
Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2301-9.
Marji J, O'Donoghue SI, McClintock D, Satagopam VP, Schneider R, Ratner D, Worman HJ, Gordon LB, Djabali K. Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition. PLoS One. 2010 Jun 15;5(6):e11132.
Wang Y, Panteleyev AA, Owens DM, Djabali K, Stewart CL, Worman HJ. Epidermal expression of the truncated prelamin A causing Hutchinson-Gilford progeria syndrome: effects on keratinocytes, hair and skin. Hum Mol Genet. 2008 Aug 1;17(15):2357-69.
Engelhard A, Bauer RC, Casta A, Djabali K, Christiano AM. Ligand-independent regulation of the hairless promoter by vitamin D receptor.
Photochem Photobiol. 2008 Mar-Apr;84(2):515-21
McClintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, Djabali K. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One. 2007 Dec 5;2(12):e1269.
Cao K, Capell BC, Erdos MR, Djabali K, Collins FS. A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4949-54.
McClintock D, Gordon LB, Djabali K. Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2154-9.
Paradisi M, McClintock D, Boguslavsky RL, Pedicelli C, Worman HJ, Djabali K. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress. BMC Cell Biol. 2005 Jun 27;6:27.
Lu X, Djabali K. Autophagic removal of farnesylated carboxy-terminal lamin peptides.
Cells. 2018 Apr 23;7(4). pii: E33. doi: 10.3390/cells7040033.
Irving Clinical Research Career Award
The Alexander von Humboldt Foundation
The Progeria Research Foundation
E-Rare-3 -2017 (JTC 2017) /DFG