Staff Profile
Dr Ralf Kist
Senior Lecturer in Oral Biology
- Email: ralf.kist@ncl.ac.uk
- Telephone: +44 (0) 191 208 8390
- Address: School of Dental Sciences
Oral Biology (Level 7, Room 7.020)
Biosciences Institute
Centre for Cancer
Faculty of Medical Sciences
Framlington Place
Newcastle upon Tyne, NE2 4BW
Introduction
I studied at the University of Freiburg, Germany and received a Diploma in Biology (equivalent to a BSc/MSc) in 1997. With a background in human genetics research, I became interested in developing mouse models for human diseases. During my PhD studies at the Helmholtz Centre for Environmental Health in Munich, I generated and characterised a mouse model for the skeletal malformation syndrome campomelic dysplasia. From 2001 to 2007, I worked as a research associate in the laboratory of Dr. Heiko Peters at the Institute of Human Genetics in Newcastle where I focused on craniofacial and tooth development in mice. In 2007, I was awarded a University Research Fellowship to develop a research theme into genetic mechanisms of oral epithelial differentiation and disease. In 2010, I was appointed Lecturer in Oral Biology at the School of Dental Sciences.
Qualifications
1997 Diploma (BSc/MSc) in Biology (University of Freiburg, Germany)
2004 PhD in Genetics (University of Freiburg, Germany)
2016 Postgraduate Certificate in Advanced Studies in Academic Practice (Newcastle University, UK)
Previous positions
2001-2007 Research Associate, Institute of Human Genetics, Newcastle University, UK
2007-2009 University Research Fellow, Institute of Human Genetics, Newcastle University, UK
2009-2010 Scientific Officer, Northgene Ltd, Newcastle upon Tyne, UK
Area of expertise
Craniofacial and tooth development
Taste and filiform papilla development
Oral and tongue epithelial differentiation
Oral disease
Oral cancer
Memberships
International Association for Dental Research
The Pathological Society of Great Britain and Ireland
Honours and Awards
2005 Mammalian Genome Prize, Mammalian Genetics and Development Workshop, London
2008 Poster Prize, Gordon Research Conference “Craniofacial Morphogenesis and Tissue Regeneration”, Lucca, Italy
2013 BDIAP Poster Prize, Edinburgh Pathology Meeting, Edinburgh
2017 Visiting Research Scholarship (3 months), Kyoto University, Japan
Google scholar: Click here.
SCOPUS: Click here.
Undergraduate Teaching
Stage 1 BDS courses: Cell Biology, Dental Physiology, Orientation and Study skills
Stage 1 BSc courses: Cellular Physiology
Stage 2 BDS course: Craniofacial and Tooth Biology
Board of Examiners (Stage 1 and Stage 2)
Personal Tutor for BDS students (all stages)
Supervisor of Biomedical Sciences BSc Research Projects (CMB3000)
Postgraduate Teaching
MRes Oral and Dental Sciences (MMB8051): Module and Programme lead
MRes Genetics of Human Development (MMB8031)
Orthodontic Postgraduate Craniofacial Study Day
Esteem Indicators
2013: Nomination for Newcastle Teaching Excellence Award ('Taught Supervisor of the Year')
2016: Shortlisted for Newcastle Teaching Excellence Award ('Taught Supervisor of the Year')
2016: Nomination for Newcastle Teaching Excellence Award ('Innovative Teaching Methods')
2016: Fellow of the Higher Education Academy
2017: Nomination for Newcastle Teaching Excellence Award ('Outstanding Contribution to Teaching; FMS')
2018: Nomination for Newcastle Teaching Excellence Award ('Outstanding Contribution to Teaching; FMS')
2021: Winner of Newcastle Teaching Excellence Award ('Taught Supervisor of the Year')
Research Interests
Craniofacial and tooth development
Taste and filiform papilla development
Cell differentiation of the oral and tongue epithelium
Genetic mechanisms of oral disease and cancer
Current Research
The epidermis of the skin and the epithelia lining the tongue and oral cavity are classified as stratified squamous epithelia and develop from a common embryological origin, the ectoderm. However, their individual characteristics and functions are substantially different suggesting that different genetic pathways regulate this regional specification. For example, the epidermis contains hair whereas filiform and taste papillae develop on the dorsal surface of the tongue. These ‘mini organs’ are comprehensively termed ectodermal appendages and their formation is regulated by reciprocal molecular interactions between epithelial and mesenchymal cells. In contrast to the intensive research efforts to understand skin development and disease, very little is known about the molecular mechanisms that control epithelial cell differentiation of the tongue and oral mucosa. As a consequence, the genetic causes or risk factors for many oral diseases have not yet been identified.
My research focuses on the identification of genes and the analysis of their interactions and functions during development and differentiation of the tongue and oral epithelium. We compare normal and abnormal formation of oral tissues in mice and humans using histology, molecular biology, transcriptomic profiling and imaging techniques. This work will lead to a better understanding of the causes of oral diseases and oral cancer and could eventually be used to develop novel or refined diagnostic tools and therapeutic approaches.
Collaborations
Dr Max Robinson, Newcastle upon Tyne Hospitals NHS Foundation Trust
Prof Nick Jakubovics, School of Dental Sciences
Dr Richard Holliday, School of Dental Sciences
Prof Neil Rajan, Translational and Clinical Research Institute
Other Expertise
I have extensive experience in mouse genetics and the generation and analysis of disease models. In my laboratory, we use a wide range of techniques such as standard molecular biology techniques, transcriptomic profiling (DNA microarrays, RNA-Sequencing, Nanostring nCounter), quantitative real-time PCR, histology, RNA in situ hybridisation, immunohistochemical staining; microscopy and image analysis, (embryonic stem) cell culture, tissue micro-dissection and organ culture.
Postgraduate Research Student Supervision
PhD Students
MRes Students
Research Administration
Dental School Research Executive Committee
FMS PGR Committee
Postgraduate Research Student Coordinator for School of Dental Sciences
Esteem Indicators
Editor: Scientific Reports
Reviewer for various journals: https://www.webofscience.com/wos/author/record/1343100
Funding
Newcastle Healthcare Charity
The Pathological Society of Great Britain and Ireland
Japan Society for the Promotion of Science
NIHR
Myrovlytis Trust
NIHR Newcastle Biomedical Research Centre
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Articles
- Trogisch FA, Abouissa A, Keles M, Birke A, Fuhrmann M, Dittrich GM, Weinzierl N, Wink E, Cordero J, Elsherbiny A, Martin-Garrido A, Grein S, Hemanna S, Hofmann E, Nicin L, Bibli SI, Airik R, Kispert A, Kist R, Quanchao S, Kürschner SW, Winkler M, Gretz N, Mogler C, Korff T, Koch PS, Dimmeler S, Dobreva G, Heineke J. Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9. Science Translational Medicine 2024, 16(736), eabq4581.
- Sathasivam HP, Kist R, Sloan P, Thomson P, Nugent M, Alexander J, Haider S, Robinson M. Predicting the clinical outcome of oral potentially malignant disorders using transcriptomic-based molecular pathology. British Journal of Cancer 2021, 125, 413-421.
- Holliday R, Chaffee BW, Jakubovics NS, Kist R, Preshaw PM. Electronic Cigarettes and Oral Health. Journal of Dental Research 2021, 100(9), 906-913.
- Khasawneh RR, Kist R, Queen R, Hussain R, Coxhead J, Schneider JE, Mohun TJ, Zaffran S, Peters H, Phillips HM, Bamforth SD. Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype. BMC Developmental Biology 2021, 21, 14.
- Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, Kist R. Gene expression changes associated with malignant transformation of oral potentially malignant disorders. Journal of Oral Pathology & Medicine 2020, 50(1), 60-67.
- Nakatomi M, Ludwig KU, Knapp M, Kist R, Lisgo S, Ohshima H, Mangold E, Peters H. Msx1 deficiency interacts with hypoxia and induces a morphogenetic regulation during lip development. Development 2020, 147(21), dev189175.
- Arai HN, Sato F, Yamamoto T, Woltjen K, Kiyonari H, Yoshimoto Y, Shukunami C, Akiyama H, Kist R, Sehara-Fujisawa A. Metalloprotease-Dependent Attenuation of BMP Signaling Restricts Cardiac Neural Crest Cell Fate. Cell Reports 2019, 29(3), 603-616.e5.
- Scharf GM, Kilian K, Cordero J, Wang Y, Grund A, Hofmann M, Froese N, Wang X, Kispert A, Kist R, Conway SJ, Geffers R, Wollert KC, Dobreva G, Bauersachs J, Heineke J. Inactivation of Sox9 in fibroblasts reduces cardiac fibrosis and inflammation. JCI Insight 2019, 4(15), e126721.
- Phillips HM, Stothard CA, Shaikh Qureshi WM, Kousa AI, BrionesLeon JA, Khasawneh RR, Sanders R, O'Loughlin C, Mazzotta S, Dodds R, Seidel K, Bates T, Nakatomi M, Cockell SJ, Schneider JE, Mohun TJ, Maehr R, Kist R, Peters H, Bamforth SD. Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis. Development 2019, 146, dev177618.
- Xiong Z, Ren S, Chen H, Liu Y, Huang C, Zhang YL, Odera JO, Chen T, Kist R, Peters H, Garman K, Sun Z, Chen X. PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-esophageal epithelium. Journal of Pathology 2018, 244(2), 164-175.
- Holliday R, Kist R, Bauld L, Preshaw PM. E-cigarettes and oral health: a balanced viewpoint. Oral Diseases 2017, 23(8), 1180-1181.
- Feederle R, Gerber JK, Middleton A, Northrup E, Kist R, Kremmer E, Peters H. Generation of Pax1/PAX1-Specific Monoclonal Antibodies. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy 2016, 35(5), 259-262.
- Holliday R, Kist R, Bauld L. E-cigarette vapour is not inert and exposure can lead to cell damage. Evidence-Based Dentistry 2016, 17, 2-3.
- Bates T, Kennedy M, Diajil A, Goodson M, Thomson P, Doran E, Farrimond H, Thavaraj S, Sloan P, Kist R, Robinson M. Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis. Cancer Epidemiology Biomarkers and Prevention 2016, 25(6), 927-935.
- Masuda T, Wahlin K, Wan J, Hu JF, Maruotti J, Yang X, Iacovelli J, Wolkow N, Kist R, Dunaief JL, Qian J, Zack DJ, Esumi N. Transcription Factor SOX9 Plays a Key Role in the Regulation of Visual Cycle Gene Expression in the Retinal Pigment Epithelium. Journal of Biological Chemistry 2014, 289(18), 12908-12921.
- 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.
- Sugimoto Y, Takimoto A, Akiyama H, Kist R, Scherer G, Nakamura T, Hiraki Y, Shukunami C. Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. Development 2013, 140(11), 2280-2288.
- Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XY, Dickman CT, Fulton DL, Lim JS, Schnabl JM, Ramos OH, Vasseur-Cognet M, de Leeuw CN, Simpson EM, Ryffel GU, Lam EW, Kist R, Wilson MS, Marco-Ferreres R, Brosens JJ, Beccari LL, Bovolenta P, Benayoun BA, Monteiro LJ, Schwenen HD, Grontved L, Wederell E, Mandrup S, Veitia RA, Chakravarthy H, Hoodless PA, Mancarelli M, Torbett BE, Banham AH, Reddy SP, Cullum RL, Liedtke M, Tschan MP, Vaz M, Rizzino A, Zannini M, Frietze S, Farnham PJ, Eijkelenboom A, Brown PJ, Laperriere D, Leprince D, de Cristofaro T, Prince KL, Putker M, Del Peso L, Camenisch G, Wenger RH, Mikula M, Rozendaal M, Mader S, Ostrowski J, Rhodes SJ, VanRechem C, Boulay G, Olechnowicz SW, Breslin MB, Lan MS, Nanan KK, Wegner M, Hou J, Mullen RD, Colvin SC, Noy PJ, Webb CF, Witek ME, Ferrell S, Daniel JM, Park J, Waldman SA, Peet DJ, Taggart M, Jayaraman PS, Karrich JJ, Blom B, Vesuna F, O'Geen H, Sun Y, Gronostajski RM, Woodcroft MW, Hough MR, Chen E, Europe-Finner N, Karolczak-Bayatti M, Bailey J, Hankinson O, Raman V, Lebrun DP, Biswal S, Harvey CJ, Debruyne JP, Hogenesch JB, Hevner RF, Heligon C, Luo XM, Blank MC, Millen KJ, Sharlin DS, Forrest D, Dahlman-Wright K, Zhao C, Mishima Y, Sinha S, Chakrabarti R, Portales-Casamar E, Sladek FM, Bradley PH, Wasserman WW. The Transcription Factor Encyclopedia. Genome Biology 2012, 13(3), R24.
- Aust JG, Gays F, Hussain F, Butcher GW, Kist R, Peters H, Brooks CG. Mice Lacking Ly49E Show Normal NK Cell Development and Provide Evidence for Probabilistic Expression of Ly49E in NK Cells and T Cells. Journal of Immunology 2011, 186(4), 2013-2023.
- Trowe MO, Shah S, Petry M, Airik R, Schuster-Gossler K, Kist R, Kispert A. Loss of Sox9 in the periotic mesenchyme affects mesenchymal expansion and differentiation, and epithelial morphogenesis during cochlea development in the mouse. Developmental Biology 2010, 342(1), 51-62.
- Airik R, Trowe MO, Foik A, Farin HF, Petry M, Schuster-Gossler K, Schweizer M, Scherer G, Kist R, Kispert A. Hydroureternephrosis due to loss of Sox9-regulated smooth muscle cell differentiation of the ureteric mesenchyme. Human Molecular Genetics 2010, 19(24), 4918-4929.
- Nakatomi M, Wang XP, Key D, Lund JJ, Turbe-Doan A, Kist R, Aw A, Chen YP, Maas RL, Peters H. Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Developmental Biology 2010, 340(2), 438-449.
- Hargus G, Kist R, Kramer J, Gerstel D, Neitz A, Scherer G, Rohwedel J. Loss of Sox9 function results in defective chondrocyte differentiation of mouse embryonic stem cells in vitro. International Journal of Developmental Biology 2008, 52(4), 323-332.
- Ehrmann I, Dalgliesh C, Tsaousi A, Paronetto MP, Heinrich B, Kist R, Cairns P, Li W, Mueller C, Jackson M, Peters H, Nayernia K, Saunders P, Mitchell M, Stamm S, Sette C, Elliott DJ. Haploinsufficiency of the germ cell-specific nuclear RNA binding protein hnRNP G-T prevents functional spermatogenesis in the mouse. Human Molecular Genetics 2008, 17(18), 2803-2818.
- Bastide P, Darido C, Pannequin J, Kist R, Robine S, Marty-Double C, Bibeau F, Scherer G, Joubert D, Hollande F, Blache P, Jay P. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. Journal of Cell Biology 2007, 178(4), 635-648.
- Lincoln J, Kist R, Scherer G, Yutzey KE. Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. Developmental Biology 2007, 305(1), 120-132.
- Seymour PA, Freude KK, Tran MN, Mayes EE, Jensen J, Kist R, Scherer G, Sander M. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(6), 1865-1870.
- Kist R, Greally E, Peters H. Derivation of a mouse model for conditional inactivation of Pax9. Genesis 2007, 45(7), 460-464.
- Barrionuevo F, Bagheri-Fam S, Klattig J, Kist R, Taketo MM, Englert C, Scherer G. Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biology of Reproduction 2006, 74(1), 195-201.
- Kist R, Watson M, Wang X, Cairns P, Miles C, Reid DJ, Peters H. Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia. Human Molecular Genetics 2005, 14(23), 3605-3617.
- Perl A-KT, Kist R, Shan Z, Scherer G, Whitsett JA. Normal lung development and function after Sox9 inactivation in the respiratory epithelium. Genesis: The Journal of Genetics and Development 2005, 41(1), 23-32.
- Jonker L, Kist R, Aw A, Wappler I, Peters H. Pax9 is required for filiform papilla development and suppresses skin-specific differentiation of the mammalian tongue epithelium. Mechanisms of Development 2004, 121(11), 1313-1322.
- Kist R, Schrewe H, Balling R, Scherer G. Conditional inactivation of Sox9: a mouse model for campomelic dysplasia. Genesis: The Journal of Genetics and Development 2002, 32(2), 121-123.
- Pfeifer D, Kist R, Dewar K, Devon K, Lander ES, Birren B, Korniszewski L, Back E, Scherer G. Campomelic dysplasia translocation breakpoints are scattered over 1 Mb proximal to SOX9: evidence for an extended control region. American Journal of Human Genetics 1999, 65(1), 111-124.
- Pusch C, Hustert E, Pfeifer D, Sudbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G. The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor. Human Genetics 1998, 103(2), 115-123.
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Review
- Chen X, Li Y, Paiboonrungruang C, Li Y, Peters H, Kist R, Xiong Z. PAX9 in cancer development. International Journal of Molecular Sciences 2022, 23(10), 5589.