Dr Julia Reichelt
- Email: email@example.com
- Telephone: +44 (0) 191 208 5074
- Fax: +44 (0) 191 208 7179
- Personal Website: http://research.ncl.ac.uk/reicheltlab/
- Address: Institute of Cellular Medicine
M2.138, William Leech Building
Newcastle upon Tyne
Roles and Responsibilities
- Lecturer on the MRes course "Stem Cells & Regenerative Medicine"
- Supervision of Postgraduates (PhD and MRes students)
- Supervision of Undergraduates
- PDR conduction
- Management of the 'Dermatological Sciences Journal Cub' and the 'Research in Progress' seminar series
- Venia legendi (PD), University of Bonn, Germany
- Habilitation (habil.) in Genetics, University of Bonn, Germany
- PhD in Human Biology (Dr. rer. physiol.), University of Marburg, Germany
- Diploma in Human Biology (major subjects: Biochemistry/Molecular Biology, Cell Biology and Immunology), University of Marburg, Germany
- PI, Biochemistry I, University of Cologne, Germany
- Assistant Professor, Institute of Physiological Chemistry, University of Bonn, Germany
- Postdoc, Institute of Physiological Chemistry, University of Bonn, Germany
- Postdoc, Institute of Genetics, University of Bonn, Germany
- The Physiological Society
- British Society for Investigative Dermatology (BSID)
- Deutscher Hochschulverband (DHV)
German, Spanish, French
Our research interest focuses on two areas: 1) keratinocyte stem cell regulation in normal and psoriatic skin, and 2) the development of gene therapies for blistering skin diseases aiming to treat patient’s keratinocyte stem cells ex vivo using the novel TALE nuclease technology. Furthermore, we have a strong background in intermediate filament research and contributed to the understanding of the role of intermediate filaments under physiological conditions and in disease.
Keratinocyte stem cells
Forcing stem cells out of their niche to improve wound healing
Skin stem cells are responsible for constant skin renewal and for wound healing. There is one population of extremely potent stem cells sitting in a niche at the interface between the hair follicle and a small muscle the contraction o which causes the hair to stand on end when we are freezing. It is known from other types of stem cells in our bodies, such as bone stem cells, that they are activated by force. Our group is investigating whether contraction of the hair follicle muscle resulting in stretching of the niche stem cells activates this cell population. If we find that skin stem cells are activated by stretch we will explore whether this mechanism may be harnessed to accelerate healing of difficult wounds.
Gene therapies for inherited skin disorders
Our research team is currently developing gene therapies for two inherited blistering skin diseases: epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EHK). The aim is to use ‘molecular scissors’ (novel tools called ‘TALE nucleases’) to destroy the disease-causing genes in skin cells from patients. As the ‘molecular scissors cannot be applied to the skin directly we will treat skin cells, derived from patient biopsies, in the laboratory and transplant successfully corrected cells back to the patient’s skin. The ‘molecular scissors’ will cause a permanent correction of the gene defects in the patient’s skin cells but will otherwise not leave any traces within the cells. The grafted cells will support regeneration of a healthy resilient skin.
Skin resilience relies on the keratin skeleton within its cells – but how does that work exactly?
Keratins are found in various cell types in our bodies, such as liver cells or skin cells. In cells of the top layer of the skin (epidermis) keratins are the most prominent proteins. The function of these cells, called keratinocytes, is to form the skin barrier which on the one side needs to be soft enough to provide flexibility for movement and on the other side needs to be resilient enough to protect us from environmental challenges such as trauma. Keratins are essential for the function of keratinocytes as they build the ‘skeleton’ of the cells. The importance of the keratin ‘skeleton’ for the stability of the skin is seen in patients with epidermolysis bullosa simplex (EBS) who carry mutations in keratins. Although the mutant keratins can still form a cell ‘skeleton’ it is extremely fragile and cannot withstand stress very well resulting in blistering and skin coming off upon the mildest touch. There is no cure for these inherited diseases and our team is currently developing a gene therapy for EBS.
There are more than 11 varieties of keratins present within distinct cell types within the epidermis but their specific roles for the stability of the skin are unknown. One of our projects addresses this question by investigating the response of keratinocytes grown in the lab and engineered to contain different sets of keratins to stretching.
Epidermal and keratinocyte response to mechanical stress.
Development of TALEN-mediated gene therapies for blistering skin diseases.
Peer reviewer for funding bodies: Wellcome Trust, British Skin Foundation (BSF), Medical Research Council (MRC), Sparks
Peer reviewer for scientific journals: Journal of Cell Science, British Journal of Dermatology, Stem Cells, BMC Cell Biology, BMC Dermatology, Experimental Dermatology, Archives of Dermatological Research, Integrative & Comparative Biology
Ichthyosis Support Group, British Skin Foundation
North Eastern Skin Research Fund, The Psoriasis Association,German Research Foundation (DFG), Newcastle Health Care Charity/Newcastle upon Tyne Hospitals NHS Charity, NorthEast England Stem Cell Institute (NESCI), The One NorthEast (ONE), Fritz Thyssen Stiftung, Bonner Forum Biomedizin, Köln Fortune
epidermal stem cells, keratinocyte stem cells, keratinocytes, epidermis, intermediate filaments, keratins, mechanical signalling, TALEN, gene therapy, epidermolysis bullosa
CMB 3000 Research Projects
MSci Biomedical Sciences Research Projects
MRes in Medical & Molecular Biosciences: Stem Cells & Regenerative Medicine
PhD student supervision
- Fischer H, Langbein L, Reichelt J, Buchberger M, Tschachler E, Eckhart L. Keratins K2 and K10 are essential for the epidermal integrity of plantar skin. Journal of Dermatological Science 2016, 81(1), 10-16.
- March O, Aushev M, Mussolino C, Cathomen T, Reichelt J. A TALEN-mediated gene therapy for epidermolytic ichthyosis. In: British Society for Gene and Cell Therapy Annual Conference. 2015, Glasgow, UK: Mary Ann Liebert, Inc. Publishers.
- Fischer H, Langbein L, Reichelt J, Praetzel-Wunder S, Buchberger M, Ghannadan M, Tschachler E, Eckhart L. Loss of Keratin K2 Expression Causes Aberrant Aggregation of K10, Hyperkeratosis, and Inflammation. Journal of Investigative Dermatology 2014, 134(10), 2579-2588.
- Kist R, Watson M, Crosier M, Robinson M, Fuchs J, Reichelt J, Peters H. The Formation of Endoderm-Derived Taste Sensory Organs Requires a Pax9-Dependent Expansion of Embryonic Taste Bud Progenitor Cells. PLoS Genetics 2014, 10(10), e1004709.
- Wang RC, Wei Y, An Z, Zou Z, White M, Reichelt J, Levine B. Akt and intermediate filaments inhibit autophagy and promote tumorigenesis through Beclin 1/14-3-3 sequestration. In: 2013 International Investigative Dermatology Meeting. 2013, Edinburgh, UK: Nature Publishing Group.
- Langbein L, Reichelt J, Eckhart L, Praetzel-Wunder S, Kittstein W, Gassler N, Schweizer J. New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice. Cell Tissue Research 2013, 354(3), 793-812.
- Fullard N, Moles A, O'Reilly S, van Laar JM, Faini D, Diboll J, Reynolds NJ, Mann DA, Reichelt J, Oakley F. The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice. American Journal of Pathology 2013, 182(6), 2109-2120.
- Wallace L, Reichelt J. Using 3D culture to investigate the role of mechanical signalling in keratinocyte stem cells. In: Turksen, K, ed. Skin Stem Cells: Methods and Protocols. New York: Springer, 2013, pp.153-164.
- Wang RC, Wei Y, Zou Z, An Z, Bhagat G, White M, Reichelt J, Levine B. Akt and keratin intermediate filaments collaborate to regulate autophagy and tumorigenesis. In: 75th Annual Meeting of the Society for Investigative Dermatology. 2012, Raleigh, North Carolina, USA: Nature Publishing Group.
- Wang RC, Wei Y, An Z, Zou Z, White M, Reichelt J, Levine B. Akt-Mediated Regulation of Autophagy and Tumorigenesis through Beclin 1 Phosphorylation. Science 2012, 338(6109), 956-959.
- Wallace L, Roberts-Thompson L, Reichelt J. Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity. Journal of Cell Science 2012, 125(7), 1750-1758.
- Höher T, Wallace L, Khan K, Cathomen T, Reichelt J. Highly Efficient Zinc-Finger Nuclease-Mediated Disruption of an eGFP Transgene in Keratinocyte Stem Cells without Impairment of Stem Cell Properties. Stem Cell Reviews and Reports 2012, 8(2), 426-434.
- Roth W, Kumar V, Beer HD, Richter M, Wohlenberg C, Reuter U, Thiering S, Staratschek-Jox A, Hofmann A, Kreusch F, Schultze JL, Vogl T, Roth J, Reichelt J, Hausser I, Magin TM. Keratin 1 maintains skin integrity and participates in an inflammatory network in skin via interleukin-18. Journal of Cell Science 2012, 125(22), 5269-5279.
- Brown AM, Todd C, Darlington H, Reynolds NJ, Reichelt J. Mitogen and stress-activated kinase 1 activation is impaired in psoriatic keratinocytes in response to mechanical stress. In: 42nd Annual Meeting of the European Society for Dermatological Research (ESDR). 2012, Venice, Italy: Nature Publishing Group.
- Vollmers A, Wallace L, Fullard N, Höher T, Alexander MD, Reichelt J. Two- and Three-Dimensional Culture of Keratinocyte Stem and Precursor Cells Derived from Primary Murine Epidermal Cultures. Stem Cell Reviews and Reports 2012, 8(2), 402-413.
- Roberts-Thompson L, Reichelt J. K1/K10 filaments are dispensable for epidermal barrier formation. In: British Journal of Dermatology. 2011, Manchester, UK: Wiley-Blackwell Publishing Ltd.
- Reichelt J, Haase I. Establishment of spontaneously immortalised keratinocyte lines from wild-type and mutant mice. In: K Turksen, ed. Epidermal Cells: Methods and Protocols. Totowa, NJ, USA: The Humana Press Inc, 2009, pp.59-69.
- Loeher M, Luebken H, Reichelt J. Keratin 10-deficient keratinocytes show altered mechanical signalling in response to stretch in differentiated cultures. In: British Journal of Dermatology: Annual Meeting of the British Society for Investigative Dermatology. 2008, Oxford, UK: Wiley-Blackwell Publishing Ltd.
- Reichelt J. Mechanotransduction of keratinocytes in culture and in the epidermis. European Journal of Cell Biology 2007, 86(11-12), 807-816.
- Hubbers CU, Clemen CS, Kesper K, Boddrich A, Hofmann A, Kamarainen O, Tolksdorf K, Stumpf M, Reichelt J, Roth U, Krause S, Watts G, Kimonis V, Wattjes MP, Reimann J, Thal DR, Biermann K, Evert BO, Lochmuller H, Wanker EE, Schoser BG, Noegel AA, Schroder R. Pathological consequences of VCP mutations on human striated muscle. Brain 2007, 130(2), 381-393.
- Fischer D, Clemen CS, Olive M, Ferrer I, Goudeau B, Roth U, Badorf P, Wattjes MP, Lutterbey G, Kral T, van der Ven PF, Furst DO, Vicart P, Goldfarb LG, Moza M, Carpen O, Reichelt J, Schroder R. Different early pathogenesis in myotilinopathy compared to primary desminopathy. Neuromuscular Disorders 2006, 16(6), 361-367.
- Magin TM, Hesse M, Meier-Bornheim R, Reichelt J. Developing mouse models to study intermediate filament function. Methods in Cell Biology 2004, 78, 65-94.
- Magin TM, Reichelt J, Hatzfeld M. Emerging functions: diseases and animal models reshape our view of the cytoskeleton. Experimental Cell Research 2004, 301(1), 91-102.
- Reichelt J, Breiden B, Sandhoff K, Magin TM. Loss of keratin 10 is accompanied by increased sebocyte proliferation and differentiation. European Journal of Cell Biology 2004, 83(11-12), 747-759.
- Reichelt J, Furstenberger G, Magin TM. Loss of Keratin 10 Leads to Mitogen-Activated Protein Kinase (MAPK) Activation, Increased Keratinocyte Turnover, and Decreased Tumour Formation in Mice. The Journal of Investigative Dermatology 2004, 123(5), 973-981.
- Kirfel J, Magin TM, Reichelt J. Keratins: a structural scaffold with emerging functions. Cellular and Molecular Life Sciences 2003, 60(1), 56-71.
- Porter R, Jahoda C, Lunny D, Henderson G, Ross J, McLean W, Whittock N, Wilson N, Reichelt J, Magin T, Lane E. 26 Mouse models for human hair loss disorders. Journal of Anatomy 2002, 201(5), 424.
- Porter RM, Jahoda CAB, Lunny DP, Henderson G, Ross J, McLean IWH, Whittock NV, Wilson NJ, Reichelt J, Magin TM, Lane EB. Defolliculated (Dfl): A dominant mouse mutation leading to poor sebaceous gland differentiation and total elimination of pelage follicles. Journal of Investigative Dermatology 2002, 119(1), 32-37.
- Reichelt J, Magin TM. Hyperproliferation, induction of c-Myc and 14-3-3σ, but no cell fragility in keratin-10-null mice. Journal of Cell Science 2002, 115(13), 2639-2650.
- Reichelt J, Schachtschabel DO. Energetic stress induces premature aging of diploid human fibroblasts (Wi-38) in vitro. Archives of Gerontology and Geriatrics 2001, 32(3), 219-231.
- Reichelt J, Bussow H, Grund C, Magin TM. Formation of a Normal Epidermis Supported by Increased Stability of Keratins 5 and 14 in Keratin 10 Null Mice. Molecular Biology of the Cell 2001, 12(6), 1557-1568.
- Reichelt J, Doering T, Schnetz E, Fartasch M, Sandhoff K, Magin TM. Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis. Journal of Investigative Dermatology 1999, 113(3), 329-34.
- Porter RM, Reichelt J, Lunny DP, Magin TM, Lane EB. The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE. J Invest Dermatol 1998, 110, 951-7.
- Reichelt J, Bauer C, Porter R, Lane E, Magin, T. Out of balance: consequences of a partial keratin 10 knockout. J Cell Sci 1997, 110, 2175-86.
- Behrens SE, Tyc K, Kastner B, Reichelt J, Luhrmann R. Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. Mol Cell Biol 1993, 13, 307-19.