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CV-BiP-02-2015

This curriculum vitae summarizes the career and qualifications of Paul Lorenz Bigliardi. He is a Swiss citizen and Singapore permanent resident who has over 30 years of experience in dermatology and allergology. He currently holds several senior positions including director of the Clinical Research Unit for Skin, Allergy and Regeneration in Singapore. His research focuses on areas such as wound healing, skin toxicology, neurodermatology, and photobiology. He has over 50 peer-reviewed publications and has received several awards and research grants over his career.

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1 CURRICULUM VITAE BIGLIARDI PAUL LORENZ Personal Data Swiss citizen, Singapore Permanent Resident Academic/Medical Certifications 2013 Full Medical licence to practice in Singapore (SMC/SAB) 2011 Associate Professor on Clinical Investigator track, NUS, Yong Loo Lin School of Medicine (rank 24th in world university ranking 2013);Invited Professor at University of Lausanne, Switzerland 2005 Privatdocent and MER (maître d’enseignement et de recherche, type 1) at the University of Lausanne, Dept. of Dermatology 2003 Privatdozent at the University of Basel, Dept. of Dermatology. Thesis: Role of the -opiate receptor system in skin physiology and pathology. Title of oral defense: Pruritus – an unsolved Problem? 2002 Honorary Professor of Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College 1999 Board certified for “Allergology and Clinical Immunology” by the Swiss Medical Association (FMH) 1998 Board certified for “Dermatology and Venereology” by the Swiss Medical Association (FMH) 1991 MD Thesis: Das maligne Melanom im Kanton Thurgau von 1970 bis 1989; University of Zürich, Switzerland. Adviser: Prof Th. Hardmeier, Head Department of Pathology, Münsterlingen 1990 Full Medical licence to practice in Switzerland 1984-1990 Medical School, Universities of Fribourg and Bern, Switzerland Employments Period Employer Position Head of Clinic/ Department 2011-now  National University of Singapore National UniversityHealth System (NUHS)  Institute for Medical Biology (IMB), A*STAR, Singapore  Senior consultant in Rheumatology / UMC (Allergy/clinical Immunology)  Director of Academic Dermatology / Allergology in University Medicine Clinic  Senior PI Experimental Dermatology group  Director of CRUSAR Law rence Ho Khek Yu Tang Ching Lau Birgit Lane 2005-2011 Department of Dermatology, University of Lausanne (CHUV) Médecin adjoint (senior consultant) and Director of outpatient clinic, day care clinic (wound care) and dermato-allergology unit, introduction of eHealth Renato Panizzon 1999-2005 Kantonsspital Schaffhausen, Department of Internal Medicine Head of Dermatology and Allergology unit with private practice in Hospital Sigi Rüttimann 1996-2005 Department of Dermatology, University of Basel, Switzerland Principal investigator ofthe research group Department of Dermatology Theo Rufli 1997-1999 Department of Allergology, University of Basel, Switzerland Clinical fellowship for the title “Allergology and Clinical Immunology” Andreas Bircher 1993-1997 Department of Dermatology, University of Basel, Switzerland Clinical fellowship for the title “Dermatology and Venereology” Theo Rufli Stan Büchner 1991-1993 Department of Dermatology, University of Minnesota, Minneapolis, USA Postdoctoral Research Experience Topics: immunomodulatory activity of yeast cell wall mannan; Acetylcholine receptors on human keratinocytes Mark V. Dahl, Robert D. Nelson Sergei A. Grando Guest lecturer in Pharmacy Institute of ETH Zürich on Dermatology for Pharmacists (2000-2005) Current Positions  Director of Clinical Research Unit for Skin, Allergy and Regeneration CRUSAR
2  Senior PI Experimental Dermatology group, Institute of Medical Biology, Agency for Science and Technology and Advanced Research (A*STAR)  Senior consultant, NUHS (Rheumatology)  Associate Professor on Clinical Investigator track, NUS, Yong Loo Lin School of Medicine  Fully certified physician in Switzerland and Singapore (SAB/SMC)  Director of Academic Dermatology/Allergology, UMC/NUH  PD University of Basel and Invited Professor University of Lausanne, Switzerland  Honorary Professor, Institute of Dermatology, Nanjing, Beijing Union Hospital, Chin Acad Sci Research Interests and current projects  Clinical and Translational Research: design and execution of clinical trials in skin, allergy and wound healing and use of novel, non-invasive laser devices (e.g. Raman spectroscopy and photoacoustics) to study healthy and diseased skin in humans  Bioengineering: biomaterials supporting growth and differentiation of various skin cells, including stem cells; study of transcutaneous absorption and development of biocompatible, non-toxic and non- sensitizing materials for topical formulation such as anti-microbial hydrogel; development of novel allo- and autografts.  Wound healing: biofilm, wound infections; wound disorders; scar formation; novel wound dressings, allografts; cross-talk between dermal and epidermal cells in wound healing  Skin Toxicology and Transcutaneous Absorption: combine and cross-validate information’s from in-vitro human 3D skin models (organotypic cultures) on microchips with in-vivo studies using novel laser devices and evaluate skin toxicology, transcutaneous absorption and metabolism of various compounds in skin  Allergology and Immunology: drug induced allergies; immunologic interactions with microbiome in skin; ethnic differences in allergic reactions; effects of pollution on allergens and immune system; role of skin barrier in skin irritation and sensitization to microbial and contact allergens  Neurodermatology: effect of neuropeptides/neurotransmitters on skin homeostasis, differentiation, adhesion and migration and role of nerve system and re-innervation in wound healing; interactions between peripheral nerves endings and skin cells; peripheral pain and itch sensation, effects of Opioids and its receptors on skin sensation, wound healing/homeostasis and circadian rhythm.  Hair biology: differential expression of genes and proteins in healthy and diseased scalp skin; role of micro-RNA in hair biology  Photobiology: study immediate and delayed effects of various light qualities (from UV to Infrared) on various skin cells in-vitro (including Opsin receptors); design novel targeted photosensitizers for photodynamic therapy; develop novel devices to study standardized and reproducible the effects of defined wave lengths on skin cells in-vitro and human skin in-vivo Awards and Grants 2014 National Medical Research Council Bench to Bedside grant: Human umbilical cord Wharton's jelly stem cells for the treatment of non-healing wounds. 2013 Co-PI for Joint Council Office (JCO) Grant, A*STAR: “Skin-on-a-chip for Standardized, Reliable and High-throughput Skin Absorption and Irritation Evaluation” 2012 Lead PI for Strategic Positioning Fund (SPF), A*STAR for creation of: Clinical Research Unit for Skin, Allergy and Regeneration (CRUSAR) 2012 PI for Joint Council Office (JCO) Grant, A*STAR: Effects of different light qualities on skin and their use in photodynamic therapy in cosmetics and skin disorders 2009 Grant from Beiersdorf, Hamburg for 2 years together with Pharmacology UNIL : « Sensitive Skin », 2007 Research grant from University of Lausanne for 3 years together with Prof Christian Widmann, DBCM: « Stress-induced survivin expression: a protective mechanism in the skin against UV- mediated damages?” 2007 Swiss National Science Foundation Research grant (grant n° 3100A0-116811): Role of delta- (DOR) and mu- (MOR) opioid receptors in skin homeostasis and wound healing
3 2005 Research funding for 2 years from LVMH, France: Role of opioid receptors in skin aging of sun- and not-sun-exposed skin in Chinese population 2003 Roche Prize 2003 of the Swiss Dermatology Society; Annual Meeting, Lausanne 2002 UPSA Pain Institute Switzerland 2002 Pain Award: 70th Annual Meeting of the Swiss Society for Internal Medicine, Geneva 2000 Research funding for 5 years from Spirig AG, Egerkingen for basic and clinical research on skin opiate receptors and its relationship to pruritus 1997 Grant from Novartis Research Foundation 1996 Swiss National Foundation grant with the title “opiate receptor expression in keratinocytes and in situ studies of opiate receptors in different human skin diseases”. 1995: "Wilhelm Lutz Award 1995" of the "Alfred Marchionini Stiftung" for the research done in the USA. Collaborations  Engineers (Prof Soo Chin Chua, IMRE and Dr. Wang Zhiping, SimTech), Chemists (Dr. Brendan Burkett, ICES) and Physicists specialized in imaging (Prof. Malini Olivo, SBIC) from A*STAR with various joint industry and public grants  Prof. Walter Wahli, UNIL and NTU on circadian rhythm  Prof. Eugene Stulz, University of Southampton, UK; joint PhD program with A*STAR (Chemically Tagged DNA probes for sensing of DNA biomarkers using Lab-on-a-chip technology  Prof. Wang Xue Ming, Shanghai Skin Hospital; exchange of physicians, collaboration in clinical research and joint grant submitted on effects of pollution in allergies  Prof. Alex Eberle, Switzerland on development of targeted photosensitizers for photodynamic therapy  Prof. Axel Hillmer, GIS/A*STAR and Dr. Markus Wenk, Lipidomics group NUS on hair biology  Prof. Venkatesan Thirumalai, NUS-NNI on effects of bio-inorganic adaptive interfaces on skin cells  Prof. Christian Surber, Galderma/UniBas and Prof. Giorgia Pastorin, NUS Pharmacy on skin formulation Functions in Societies and Meeting organisations  Director of Swiss Contact Dermatitis Research Group SGDV from 2005-2010  Organizational and Scientific Director of 90th Annual Meeting of SGDV, Lausanne; 2008  Organizer of bi-annual Dermato-Allergology Workshop of SGDV; 2009  Board member of the International Narcotics Research Conference INRC since 2014 Industrial Experience Scientific collaborations, joint projects and scientific advisor with: - Spirig AG, Switzerland - Knorr/Unilever, Switzerland - LVMH, France - DSM, Switzerland - Beiersdorf, Germany - Organogenesis, USA - Biomed Inc., Singapore and Thermo Fischer, USA - L’Oréal, France - Procter & Gamble (P&G), USA - Mundipharma Gmbh, Switzerland, Germany and USA Memberships Schweizerische Gesellschaft für Dermatologie und Venereologie SGDV (since 1990) Schweizerische Gesellschaft für Allergologie und klinische Immunologie SGAI (since 1994) American Academy of Dermatology (since 1991) European Academy of Allergy and Clinical Immunology (since1999) European Tissue Repair Society (since 2004) International Narcotics Research Conf INRC (since 2005) Singapore Academy of Medical Sciences (since 2012)
4 References Professor Mark V. Dahl Professor R. Panizzon Chairman of Dept. of Dermatology Dept. of Dermatology Mayo Clinic University of Lausanne, CHUV Scottsdale, AZ 85259 Hôpital Beaumont USA CH-1011 Lausanne Dahl.MarkV@mayo.edu renato.panizzon@chuv.ch Prof. Yann Barrandon Prof. Stan Buechner Head of Laboratory of Stem Cell Dynamics Blumenrain 20 Ecole Polytechnique Federale de Lausanne (EPFL) Basel EPFL SV IBI LDCS stanislaw.buechner@hin.ch CH-1015 Lausanne yann.barrandon@epfl.ch Military rank and function Major; organizing officer International Committee of Military Medicine (ICMM), Swiss Armed Forces) Contact information’s phone : ++65 9137 2324 E-mail : paul_bigliardi@nuhs.edu.sg or paul.bigliardi@yahoo.com Private address: 222A Ocean Drive #06-28; Singapore 098619
5 List of publications # Peer-reviewed publications 1 Grando SA, Cabrera R, Hostager BS, Bigliardi PL, Blake JS, Herron MJ, Dahl MV and Nelson RD: Computerized microassay of keratinocyte cell-plastic attachment and proliferation for assessing net stimulatory, inhibitory and toxic effects of compounds on nonimmortalized cell lines. Skin Pharmacol 6: 135-47, 1993 2 Bigliardi PL, Herron MJ, Nelson RD and Dahl MV: Effects of detergents on proliferation and metabolism of human keratinocytes. Exp Dermatol 3: 89-94, 1994 3 Grando SA, Zelickson BD, Kist DA, Weinshenker D, Bigliardi PL, Wendelschafer-Crabb G, Kennedy WR and Dahl MV: Keratinocyte muscarinic acetylcholine receptors: immunolocalization and partial characterization. J Invest Dermatol 104: 95-100, 1995 4 Bigliardi PL, Bigliardi-Qi M, Büchner S and Rufli T: Expression of mu-opiate receptor in human epidermis and keratinocytes. J Invest Dermatol 111: 297-301, 1998 5 Moins-Teisserenc HT, Gadola SD, Cella M, Dunbar PR, Exley A, Blake N, Baykal C, Lambert J, Bigliardi P, Willemsen M, Jones M, Büchner S, Colonna M, Gross WL, Cerundolo V and Baycal C: Association of a syndrome resembling Wegener's granulomatosis with low surface expression of HLA class-I molecules. Lancet 354: 1598-603, 1999 6 Bircher AJ, Bigliardi P and Yilmaz B: Anaphylaxis resulting from selective sensitization to Americana grapes. J Allergy Clin Immunol 104: 1111-3, 1999 7 Bircher AJ, Bigliardi P, Langauer Messmer S and Surber C: Occupational airborne contact dermatitis from diphencyprone in a pharmacy employee. Contact Dermatitis 41: 52, 1999 8 Bigliardi-Qi M, Bigliardi PL, Büchner S and Rufli T: Characterization of mu-opiate receptor in human epidermis and keratinocytes. Ann N Y Acad Sci 885: 368-71., 1999 9 Bircher AJ, Bigliardi P, Zaugg T and Makinen-Kiljunen S: Delayed generalized allergic reactions to corticosteroids. Dermatology 200: 349-51, 2000 10 Bigliardi-Qi M, Bigliardi PL, Eberle AN, Büchner S and Rufli T: beta-endorphin stimulates cytokeratin 16 expression and downregulates mu-opiate receptor expression in human epidermis. J Invest Dermatol 114: 527-32, 2000 11 Bigliardi PL, Büchner S, Rufli T and Bigliardi-Qi M: Specific stimulation of migration of human keratinocytes by -opiate receptor agonists. J Recept Signal Transduct Res 22: 191-199, 2002 12 Bigliardi PL, Sumanovski LT, Büchner S, Eberle AN, Rufli T and Bigliardi-Qi M: Different expression of - opiate receptor in chronic and acute wounds and the effect of -endorphin on TGF- type II receptor and cytokeratin 16 expression. J Invest Dermatol 120: 145-152, 2003 13 Bigliardi PL, Izakovic J, Weber JM and Bircher AJ: Anaphylaxis to the carbohydrate carboxymethylcellulose in parenteral corticosteroid preparations. Dermatology 207: 100-103, 2003 14 Bigliardi PL, Braschler C, Kuhn P, Sigrist J, Büchner S and Rufli T: Unilateral aplasia cutis congenita on the leg. Pediatric Dermatol 21: 454 –457, 2004 15 Bigliardi-Qi M, Sumanovski L, Büchner S, Rufli T and Bigliardi PL: -opiate receptor and -endorphin expression in nerve endings and keratinocytes in human skin. Dermatology 209:183-189,2004 16 Bigliardi-Qi M, Lipp B, Sumanovski LT, Büchner S and Bigliardi PL: Changes of epidermal mu-opiate receptor expression and nerve endings in chronic atopic dermatitits. Dermatology 210: 91-99, 2005 17 Bigliardi PL and Bigliardi-Qi M: Controversies in Experimental Dermatology: How best to treat that nasty itch – From new insights into the neuroimmunology, neuroendocrinology and neurophysiology of pruritus to novel therapeutic approaches. Exp Dermatol 14: 236-237, 2005 18 Bigliardi PL: PRURIT: causes, diagnostic et traitement. Revue Medicale Suisse 2: 1115-21, 2006 19 Bigliardi-Qi M, Gaveriaux-Ruff C, Zhou H, Hell C, Bady P, Rufli T, Kieffer B and Bigliardi PL: Deletion of delta opioid receptor in mice alters skin differentiation and delays wound healing. Differentiation 74: 174-185, 2006 20 Bigliardi PL: Ursachen, Diagnose und Therapie von Pruritus. Aktuelle Dermatologie 32:468-473, 2006 21 Bigliardi-Qi M, Gaveriaux-Ruff C, Pfaltz K, Bady P, Baumann T, Rufli T, Kieffer B and Bigliardi PL: Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings and itch behavior. J Invest Dermatol 127: 1479-88, 2007 22 Bigliardi PL, Stammer H, Jost G, Rufli T, Büchner S and Bigliardi-Qi M: Treatment of chronic pruritus in atopic dermatitis with topically applied opiate-receptor antagonist Naltrexone: Open pilot study and randomized, placebo-controlled, cross-over trial. J Am Acad Dermatol 56: 979-88, 2007 23 Bigliardi PL, Raffoul W and Berger MM: Toxic Epidermal Necrolysis. Revue Medicale Suisse 3: 1112-8, 2007 24 Bigliardi PL: Wenn sich der Patient die Haut vom Leibe kratzen könnte – was hilft? Dermatologie Praxis 2: 24- 26, 2007
6 25 Bigliardi PL: Pruritus – Therapie bei verschiedenen Grunderkrankungen Dermatologie Praxis 32: 20-22, 2007 26 Bigliardi PL, Gabard B and Vogel-Kahmann I: Update – Kortikosteroide zur lokalen Anwendung auf der Haut. Pharmakritik 30 : 29-36, 8/9/2008. 27 Bigliardi-Qi M, Noblesse E, Chen ZQ, Gao FL, Bigliardi PL and Bonte F: Role of Opioid Receptors in Skin. Chinese Journal of Dermatology 41:8; 6-8, 2008 28 Bigliardi PL, Gaveriaux-Ruff C, Tobin D and Bigliardi-Qi M: Opioids and the skin – where do we stand?.Viewpoint-article. Experimental Dermatology 18:424-430, 2009 29 Grasset N, Raffoul W and Bigliardi PL: Pansements Bioactifs (nouveautés en medecine 2009). Revue Medicale Suisse 6:354-7, 2010 30 Grouzmann E, Bigliardi PL, Appenzeller M, Pannatier A, Buclin T: Substance P induced skin inflammation is not modulated by a single dose of Sitagliptin in human volunteers; J Biol Chem 392:217-21, 2011 31 Spring P and Bigliardi P: Chronic hand eczema, conventional and new treatments; Rev Med Suisse 4:8: 736-742, 2012 32 Peltzer N, Bigliardi P and Widmann C: UV-B induces cytoplasmic survivin expression in mouse epidermis; J Dermatol Sci, 67:3: 196-199, 2012 33 Khalil H, Peltzer N, Walicki J, Yang JY, Dubuis G, Gardiol N, Held W, Bigliardi P, Marsland B, Liaudet L and Widmann C: Caspase-3 protects stressed organs against cell death; Mol Cell Biol, 32:22: 4523-4533, 2012 34 Spring P, Angelillo-Scherrer A and Bigliardi PL: Chronic Idiopathic Urticaria successfully treated by anticoagulant drugs. Eur J Dermatol, 22:6:788-90, 2012 35 Bigliardi PL, Neumann C, Teo YL, Pant A and Bigliardi-Qi M: Activation of the delta-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration. Br J Pharmacol, ePub DOI 10.1111/bph.12687, 2014. 36 Bigliardi PL: Pruritus im Alter (Pruritus senilis). Dermatologie Praxis, Vol 24, No2, 2014 37 Thalayasingam M, Allameen NA, Soh JY, Bigliardi PL, Van Bever H and Shek LP: Wheat-Dependent Exercise- Induced Anaphylaxis: a retrospective case review from a tertiary hospital. Postgraduate Medical Journal, Vol 90/1067, p 488-92, 2014 38 Neumann C, Bigliardi-Qi M, Widmann C and Bigliardi PL: The δ-Opioid Receptor Affects Epidermal Homeostasis via ERK-Dependent Inhibition of Transcription Factor POU2F3. J Invest Dermatol, DOI 10.1038/jid.2014.370, 2014 39 Cerny D, Shin A, Haniffa M, Bigliardi PL, Tan BK, Lee B, Poidinger M, Tan EY, Ginhoux F and Fink K: Selective susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection. PLOS Pathogens, Published: December 04, 2014; DOI: 10.1371/journal.ppat.1004548 40 Bigliardi-Qi M and Bigliardi PL: The role of opioid receptors in migration and wound recovery in-vitro in cultured human keratinocytes and fibroblasts. Methods Mol Biol, 1230, p273-7, 2015 41 Santosa E, Andiappan A, Rotzschke O, Wong HC, Marti HP, Chang A, Bigliardi-Qi M, Wang DY and Bigliardi PL: Evaluation of the applicability of the Immuno-solid-phase allergen chip (ISAC) assay in atopic patients in Singapore. Clinical and Translational Allergy, 2015, 5:9 42 Jing Hui Yik, Sandeep Jacob Sebastin, Lingaraj Krishna, Bigliardi PL: Pyoderma Gangrenosum Mimicking Early Acute Infection Following Total Knee Arthroplasty. Annals Acad Med Singapore, accepted for publication 10.2014 (publication April 2015). 43 Bigliardi-Qi M and Bigliardi PL: Review article - The role of opioid receptors in wound healing. Submitted to Receptors and Clinical Investigation, 08.2014 44 Ford S, Sardella T, Urich A, Burton NC, Kacprowicz M, Bigliardi M, Olivo M, Bigliardi PL and Razansky D. Structural and functional analysis of intact hair follicles and pilosebaceous units by volumetric multispectral optoacoustic tomography. Submitted to J Invest Dermatol, 11. 2014 (JID-2014-1036) 45 Dancik Y, Bigliardi PL, Bigliardi-Qi M and Jaworska J: Integrating dermal exposure scenarios in developmental and reproductive toxicity studies. Submitted to Reproductive Toxicology 11.2014 46 Gopu S, Bigliardi PL & Bigliardi-Qi M:Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Submitted to European J Cell Biol, 04. 2015 Book chapters 1 Itch: Basic Mechanisms and Therapy. Edited by Yosipovitch G, Greaves MV, Fleischer AB, McGlone F. Chapter 10 “Peripheral Opiate Receptor System in Human Epidermis and Itch “ by Bigliardi-Qi M and Bigliardi PL; pages 97-107 in Marcel Dekker, Inc., New York, Basel, January, 2004 2 Itch: Mechanisms and Treatment. Edited by Carstens E and Akiyama T:Chapter “Peripheral Opioids“ by Bigliardi PL and Bigliardi-Qi M. Series title “Frontiers in Neuroscience”, Taylor & Francis Group, London, 2014 Patent filings
7 1 USE OF SELECTIVE DELTA-OPIOID RECEPTOR MODIFIERS AND SPECIFIC SENSORY RECEPTOR LIGANDS. Inventors: Bigliardi-Qi M and Bigliardi PL. Pending patent (PCP filed 02.2014; No PCT/SG2014/000025) 2 Multi-spectral calibrated light source for long term cell culture study. Inventors: Paul Lorenz BIGLIARDI (IMB); CHUA Soo Jin (NUS; IMRE); TAY Chuan Beng (NUS); WANG Ben Zhong (IMRE); Mei BIGLIARDI-QI (IMB); Institutions: IMB, IMRE, NUS, Provisional SG Patent application filed 6.3.2015; Application No: 10201501747P 3 SUBMITTED: Co-Culture Device With Self-Refilling Of Culture Media Inventors: Wu Ruige; Seah Yen Peng Daphne; Wang Zhiping; Paul Lorenz Bigliardi (IMB); Mei Bigliardi-Qi (IMB); Viknish Krishnan Kutty (IMB). ETPL Ref: SIM/Z/08863; SIMTech Ref: rgwu-688 4 SUBMITTED: Thin Film Deposited Inorganic Metal Oxide as a Selective Substrate for Mammalian Cell Culture Inventors: Dykas Michal Marcin, Poddar Kingshuk, Thirumalai Venky Venkatesan, Krishnan Kutty Viknish, Bigliardi Paul, Bigliardi Mei. NUS Ref.

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CV-BiP-02-2015

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    1 CURRICULUM VITAE BIGLIARDI PAULLORENZ Personal Data Swiss citizen, Singapore Permanent Resident Academic/Medical Certifications 2013 Full Medical licence to practice in Singapore (SMC/SAB) 2011 Associate Professor on Clinical Investigator track, NUS, Yong Loo Lin School of Medicine (rank 24th in world university ranking 2013);Invited Professor at University of Lausanne, Switzerland 2005 Privatdocent and MER (maître d’enseignement et de recherche, type 1) at the University of Lausanne, Dept. of Dermatology 2003 Privatdozent at the University of Basel, Dept. of Dermatology. Thesis: Role of the -opiate receptor system in skin physiology and pathology. Title of oral defense: Pruritus – an unsolved Problem? 2002 Honorary Professor of Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College 1999 Board certified for “Allergology and Clinical Immunology” by the Swiss Medical Association (FMH) 1998 Board certified for “Dermatology and Venereology” by the Swiss Medical Association (FMH) 1991 MD Thesis: Das maligne Melanom im Kanton Thurgau von 1970 bis 1989; University of Zürich, Switzerland. Adviser: Prof Th. Hardmeier, Head Department of Pathology, Münsterlingen 1990 Full Medical licence to practice in Switzerland 1984-1990 Medical School, Universities of Fribourg and Bern, Switzerland Employments Period Employer Position Head of Clinic/ Department 2011-now  National University of Singapore National UniversityHealth System (NUHS)  Institute for Medical Biology (IMB), A*STAR, Singapore  Senior consultant in Rheumatology / UMC (Allergy/clinical Immunology)  Director of Academic Dermatology / Allergology in University Medicine Clinic  Senior PI Experimental Dermatology group  Director of CRUSAR Law rence Ho Khek Yu Tang Ching Lau Birgit Lane 2005-2011 Department of Dermatology, University of Lausanne (CHUV) Médecin adjoint (senior consultant) and Director of outpatient clinic, day care clinic (wound care) and dermato-allergology unit, introduction of eHealth Renato Panizzon 1999-2005 Kantonsspital Schaffhausen, Department of Internal Medicine Head of Dermatology and Allergology unit with private practice in Hospital Sigi Rüttimann 1996-2005 Department of Dermatology, University of Basel, Switzerland Principal investigator ofthe research group Department of Dermatology Theo Rufli 1997-1999 Department of Allergology, University of Basel, Switzerland Clinical fellowship for the title “Allergology and Clinical Immunology” Andreas Bircher 1993-1997 Department of Dermatology, University of Basel, Switzerland Clinical fellowship for the title “Dermatology and Venereology” Theo Rufli Stan Büchner 1991-1993 Department of Dermatology, University of Minnesota, Minneapolis, USA Postdoctoral Research Experience Topics: immunomodulatory activity of yeast cell wall mannan; Acetylcholine receptors on human keratinocytes Mark V. Dahl, Robert D. Nelson Sergei A. Grando Guest lecturer in Pharmacy Institute of ETH Zürich on Dermatology for Pharmacists (2000-2005) Current Positions  Director of Clinical Research Unit for Skin, Allergy and Regeneration CRUSAR
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    2  Senior PIExperimental Dermatology group, Institute of Medical Biology, Agency for Science and Technology and Advanced Research (A*STAR)  Senior consultant, NUHS (Rheumatology)  Associate Professor on Clinical Investigator track, NUS, Yong Loo Lin School of Medicine  Fully certified physician in Switzerland and Singapore (SAB/SMC)  Director of Academic Dermatology/Allergology, UMC/NUH  PD University of Basel and Invited Professor University of Lausanne, Switzerland  Honorary Professor, Institute of Dermatology, Nanjing, Beijing Union Hospital, Chin Acad Sci Research Interests and current projects  Clinical and Translational Research: design and execution of clinical trials in skin, allergy and wound healing and use of novel, non-invasive laser devices (e.g. Raman spectroscopy and photoacoustics) to study healthy and diseased skin in humans  Bioengineering: biomaterials supporting growth and differentiation of various skin cells, including stem cells; study of transcutaneous absorption and development of biocompatible, non-toxic and non- sensitizing materials for topical formulation such as anti-microbial hydrogel; development of novel allo- and autografts.  Wound healing: biofilm, wound infections; wound disorders; scar formation; novel wound dressings, allografts; cross-talk between dermal and epidermal cells in wound healing  Skin Toxicology and Transcutaneous Absorption: combine and cross-validate information’s from in-vitro human 3D skin models (organotypic cultures) on microchips with in-vivo studies using novel laser devices and evaluate skin toxicology, transcutaneous absorption and metabolism of various compounds in skin  Allergology and Immunology: drug induced allergies; immunologic interactions with microbiome in skin; ethnic differences in allergic reactions; effects of pollution on allergens and immune system; role of skin barrier in skin irritation and sensitization to microbial and contact allergens  Neurodermatology: effect of neuropeptides/neurotransmitters on skin homeostasis, differentiation, adhesion and migration and role of nerve system and re-innervation in wound healing; interactions between peripheral nerves endings and skin cells; peripheral pain and itch sensation, effects of Opioids and its receptors on skin sensation, wound healing/homeostasis and circadian rhythm.  Hair biology: differential expression of genes and proteins in healthy and diseased scalp skin; role of micro-RNA in hair biology  Photobiology: study immediate and delayed effects of various light qualities (from UV to Infrared) on various skin cells in-vitro (including Opsin receptors); design novel targeted photosensitizers for photodynamic therapy; develop novel devices to study standardized and reproducible the effects of defined wave lengths on skin cells in-vitro and human skin in-vivo Awards and Grants 2014 National Medical Research Council Bench to Bedside grant: Human umbilical cord Wharton's jelly stem cells for the treatment of non-healing wounds. 2013 Co-PI for Joint Council Office (JCO) Grant, A*STAR: “Skin-on-a-chip for Standardized, Reliable and High-throughput Skin Absorption and Irritation Evaluation” 2012 Lead PI for Strategic Positioning Fund (SPF), A*STAR for creation of: Clinical Research Unit for Skin, Allergy and Regeneration (CRUSAR) 2012 PI for Joint Council Office (JCO) Grant, A*STAR: Effects of different light qualities on skin and their use in photodynamic therapy in cosmetics and skin disorders 2009 Grant from Beiersdorf, Hamburg for 2 years together with Pharmacology UNIL : « Sensitive Skin », 2007 Research grant from University of Lausanne for 3 years together with Prof Christian Widmann, DBCM: « Stress-induced survivin expression: a protective mechanism in the skin against UV- mediated damages?” 2007 Swiss National Science Foundation Research grant (grant n° 3100A0-116811): Role of delta- (DOR) and mu- (MOR) opioid receptors in skin homeostasis and wound healing
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    3 2005 Research fundingfor 2 years from LVMH, France: Role of opioid receptors in skin aging of sun- and not-sun-exposed skin in Chinese population 2003 Roche Prize 2003 of the Swiss Dermatology Society; Annual Meeting, Lausanne 2002 UPSA Pain Institute Switzerland 2002 Pain Award: 70th Annual Meeting of the Swiss Society for Internal Medicine, Geneva 2000 Research funding for 5 years from Spirig AG, Egerkingen for basic and clinical research on skin opiate receptors and its relationship to pruritus 1997 Grant from Novartis Research Foundation 1996 Swiss National Foundation grant with the title “opiate receptor expression in keratinocytes and in situ studies of opiate receptors in different human skin diseases”. 1995: "Wilhelm Lutz Award 1995" of the "Alfred Marchionini Stiftung" for the research done in the USA. Collaborations  Engineers (Prof Soo Chin Chua, IMRE and Dr. Wang Zhiping, SimTech), Chemists (Dr. Brendan Burkett, ICES) and Physicists specialized in imaging (Prof. Malini Olivo, SBIC) from A*STAR with various joint industry and public grants  Prof. Walter Wahli, UNIL and NTU on circadian rhythm  Prof. Eugene Stulz, University of Southampton, UK; joint PhD program with A*STAR (Chemically Tagged DNA probes for sensing of DNA biomarkers using Lab-on-a-chip technology  Prof. Wang Xue Ming, Shanghai Skin Hospital; exchange of physicians, collaboration in clinical research and joint grant submitted on effects of pollution in allergies  Prof. Alex Eberle, Switzerland on development of targeted photosensitizers for photodynamic therapy  Prof. Axel Hillmer, GIS/A*STAR and Dr. Markus Wenk, Lipidomics group NUS on hair biology  Prof. Venkatesan Thirumalai, NUS-NNI on effects of bio-inorganic adaptive interfaces on skin cells  Prof. Christian Surber, Galderma/UniBas and Prof. Giorgia Pastorin, NUS Pharmacy on skin formulation Functions in Societies and Meeting organisations  Director of Swiss Contact Dermatitis Research Group SGDV from 2005-2010  Organizational and Scientific Director of 90th Annual Meeting of SGDV, Lausanne; 2008  Organizer of bi-annual Dermato-Allergology Workshop of SGDV; 2009  Board member of the International Narcotics Research Conference INRC since 2014 Industrial Experience Scientific collaborations, joint projects and scientific advisor with: - Spirig AG, Switzerland - Knorr/Unilever, Switzerland - LVMH, France - DSM, Switzerland - Beiersdorf, Germany - Organogenesis, USA - Biomed Inc., Singapore and Thermo Fischer, USA - L’Oréal, France - Procter & Gamble (P&G), USA - Mundipharma Gmbh, Switzerland, Germany and USA Memberships Schweizerische Gesellschaft für Dermatologie und Venereologie SGDV (since 1990) Schweizerische Gesellschaft für Allergologie und klinische Immunologie SGAI (since 1994) American Academy of Dermatology (since 1991) European Academy of Allergy and Clinical Immunology (since1999) European Tissue Repair Society (since 2004) International Narcotics Research Conf INRC (since 2005) Singapore Academy of Medical Sciences (since 2012)
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    4 References Professor Mark V.Dahl Professor R. Panizzon Chairman of Dept. of Dermatology Dept. of Dermatology Mayo Clinic University of Lausanne, CHUV Scottsdale, AZ 85259 Hôpital Beaumont USA CH-1011 Lausanne [email protected] [email protected] Prof. Yann Barrandon Prof. Stan Buechner Head of Laboratory of Stem Cell Dynamics Blumenrain 20 Ecole Polytechnique Federale de Lausanne (EPFL) Basel EPFL SV IBI LDCS [email protected] CH-1015 Lausanne [email protected] Military rank and function Major; organizing officer International Committee of Military Medicine (ICMM), Swiss Armed Forces) Contact information’s phone : ++65 9137 2324 E-mail : [email protected] or [email protected] Private address: 222A Ocean Drive #06-28; Singapore 098619
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    5 List of publications #Peer-reviewed publications 1 Grando SA, Cabrera R, Hostager BS, Bigliardi PL, Blake JS, Herron MJ, Dahl MV and Nelson RD: Computerized microassay of keratinocyte cell-plastic attachment and proliferation for assessing net stimulatory, inhibitory and toxic effects of compounds on nonimmortalized cell lines. Skin Pharmacol 6: 135-47, 1993 2 Bigliardi PL, Herron MJ, Nelson RD and Dahl MV: Effects of detergents on proliferation and metabolism of human keratinocytes. Exp Dermatol 3: 89-94, 1994 3 Grando SA, Zelickson BD, Kist DA, Weinshenker D, Bigliardi PL, Wendelschafer-Crabb G, Kennedy WR and Dahl MV: Keratinocyte muscarinic acetylcholine receptors: immunolocalization and partial characterization. J Invest Dermatol 104: 95-100, 1995 4 Bigliardi PL, Bigliardi-Qi M, Büchner S and Rufli T: Expression of mu-opiate receptor in human epidermis and keratinocytes. J Invest Dermatol 111: 297-301, 1998 5 Moins-Teisserenc HT, Gadola SD, Cella M, Dunbar PR, Exley A, Blake N, Baykal C, Lambert J, Bigliardi P, Willemsen M, Jones M, Büchner S, Colonna M, Gross WL, Cerundolo V and Baycal C: Association of a syndrome resembling Wegener's granulomatosis with low surface expression of HLA class-I molecules. Lancet 354: 1598-603, 1999 6 Bircher AJ, Bigliardi P and Yilmaz B: Anaphylaxis resulting from selective sensitization to Americana grapes. J Allergy Clin Immunol 104: 1111-3, 1999 7 Bircher AJ, Bigliardi P, Langauer Messmer S and Surber C: Occupational airborne contact dermatitis from diphencyprone in a pharmacy employee. Contact Dermatitis 41: 52, 1999 8 Bigliardi-Qi M, Bigliardi PL, Büchner S and Rufli T: Characterization of mu-opiate receptor in human epidermis and keratinocytes. Ann N Y Acad Sci 885: 368-71., 1999 9 Bircher AJ, Bigliardi P, Zaugg T and Makinen-Kiljunen S: Delayed generalized allergic reactions to corticosteroids. Dermatology 200: 349-51, 2000 10 Bigliardi-Qi M, Bigliardi PL, Eberle AN, Büchner S and Rufli T: beta-endorphin stimulates cytokeratin 16 expression and downregulates mu-opiate receptor expression in human epidermis. J Invest Dermatol 114: 527-32, 2000 11 Bigliardi PL, Büchner S, Rufli T and Bigliardi-Qi M: Specific stimulation of migration of human keratinocytes by -opiate receptor agonists. J Recept Signal Transduct Res 22: 191-199, 2002 12 Bigliardi PL, Sumanovski LT, Büchner S, Eberle AN, Rufli T and Bigliardi-Qi M: Different expression of - opiate receptor in chronic and acute wounds and the effect of -endorphin on TGF- type II receptor and cytokeratin 16 expression. J Invest Dermatol 120: 145-152, 2003 13 Bigliardi PL, Izakovic J, Weber JM and Bircher AJ: Anaphylaxis to the carbohydrate carboxymethylcellulose in parenteral corticosteroid preparations. Dermatology 207: 100-103, 2003 14 Bigliardi PL, Braschler C, Kuhn P, Sigrist J, Büchner S and Rufli T: Unilateral aplasia cutis congenita on the leg. Pediatric Dermatol 21: 454 –457, 2004 15 Bigliardi-Qi M, Sumanovski L, Büchner S, Rufli T and Bigliardi PL: -opiate receptor and -endorphin expression in nerve endings and keratinocytes in human skin. Dermatology 209:183-189,2004 16 Bigliardi-Qi M, Lipp B, Sumanovski LT, Büchner S and Bigliardi PL: Changes of epidermal mu-opiate receptor expression and nerve endings in chronic atopic dermatitits. Dermatology 210: 91-99, 2005 17 Bigliardi PL and Bigliardi-Qi M: Controversies in Experimental Dermatology: How best to treat that nasty itch – From new insights into the neuroimmunology, neuroendocrinology and neurophysiology of pruritus to novel therapeutic approaches. Exp Dermatol 14: 236-237, 2005 18 Bigliardi PL: PRURIT: causes, diagnostic et traitement. Revue Medicale Suisse 2: 1115-21, 2006 19 Bigliardi-Qi M, Gaveriaux-Ruff C, Zhou H, Hell C, Bady P, Rufli T, Kieffer B and Bigliardi PL: Deletion of delta opioid receptor in mice alters skin differentiation and delays wound healing. Differentiation 74: 174-185, 2006 20 Bigliardi PL: Ursachen, Diagnose und Therapie von Pruritus. Aktuelle Dermatologie 32:468-473, 2006 21 Bigliardi-Qi M, Gaveriaux-Ruff C, Pfaltz K, Bady P, Baumann T, Rufli T, Kieffer B and Bigliardi PL: Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings and itch behavior. J Invest Dermatol 127: 1479-88, 2007 22 Bigliardi PL, Stammer H, Jost G, Rufli T, Büchner S and Bigliardi-Qi M: Treatment of chronic pruritus in atopic dermatitis with topically applied opiate-receptor antagonist Naltrexone: Open pilot study and randomized, placebo-controlled, cross-over trial. J Am Acad Dermatol 56: 979-88, 2007 23 Bigliardi PL, Raffoul W and Berger MM: Toxic Epidermal Necrolysis. Revue Medicale Suisse 3: 1112-8, 2007 24 Bigliardi PL: Wenn sich der Patient die Haut vom Leibe kratzen könnte – was hilft? Dermatologie Praxis 2: 24- 26, 2007
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    6 25 Bigliardi PL:Pruritus – Therapie bei verschiedenen Grunderkrankungen Dermatologie Praxis 32: 20-22, 2007 26 Bigliardi PL, Gabard B and Vogel-Kahmann I: Update – Kortikosteroide zur lokalen Anwendung auf der Haut. Pharmakritik 30 : 29-36, 8/9/2008. 27 Bigliardi-Qi M, Noblesse E, Chen ZQ, Gao FL, Bigliardi PL and Bonte F: Role of Opioid Receptors in Skin. Chinese Journal of Dermatology 41:8; 6-8, 2008 28 Bigliardi PL, Gaveriaux-Ruff C, Tobin D and Bigliardi-Qi M: Opioids and the skin – where do we stand?.Viewpoint-article. Experimental Dermatology 18:424-430, 2009 29 Grasset N, Raffoul W and Bigliardi PL: Pansements Bioactifs (nouveautés en medecine 2009). Revue Medicale Suisse 6:354-7, 2010 30 Grouzmann E, Bigliardi PL, Appenzeller M, Pannatier A, Buclin T: Substance P induced skin inflammation is not modulated by a single dose of Sitagliptin in human volunteers; J Biol Chem 392:217-21, 2011 31 Spring P and Bigliardi P: Chronic hand eczema, conventional and new treatments; Rev Med Suisse 4:8: 736-742, 2012 32 Peltzer N, Bigliardi P and Widmann C: UV-B induces cytoplasmic survivin expression in mouse epidermis; J Dermatol Sci, 67:3: 196-199, 2012 33 Khalil H, Peltzer N, Walicki J, Yang JY, Dubuis G, Gardiol N, Held W, Bigliardi P, Marsland B, Liaudet L and Widmann C: Caspase-3 protects stressed organs against cell death; Mol Cell Biol, 32:22: 4523-4533, 2012 34 Spring P, Angelillo-Scherrer A and Bigliardi PL: Chronic Idiopathic Urticaria successfully treated by anticoagulant drugs. Eur J Dermatol, 22:6:788-90, 2012 35 Bigliardi PL, Neumann C, Teo YL, Pant A and Bigliardi-Qi M: Activation of the delta-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration. Br J Pharmacol, ePub DOI 10.1111/bph.12687, 2014. 36 Bigliardi PL: Pruritus im Alter (Pruritus senilis). Dermatologie Praxis, Vol 24, No2, 2014 37 Thalayasingam M, Allameen NA, Soh JY, Bigliardi PL, Van Bever H and Shek LP: Wheat-Dependent Exercise- Induced Anaphylaxis: a retrospective case review from a tertiary hospital. Postgraduate Medical Journal, Vol 90/1067, p 488-92, 2014 38 Neumann C, Bigliardi-Qi M, Widmann C and Bigliardi PL: The δ-Opioid Receptor Affects Epidermal Homeostasis via ERK-Dependent Inhibition of Transcription Factor POU2F3. J Invest Dermatol, DOI 10.1038/jid.2014.370, 2014 39 Cerny D, Shin A, Haniffa M, Bigliardi PL, Tan BK, Lee B, Poidinger M, Tan EY, Ginhoux F and Fink K: Selective susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection. PLOS Pathogens, Published: December 04, 2014; DOI: 10.1371/journal.ppat.1004548 40 Bigliardi-Qi M and Bigliardi PL: The role of opioid receptors in migration and wound recovery in-vitro in cultured human keratinocytes and fibroblasts. Methods Mol Biol, 1230, p273-7, 2015 41 Santosa E, Andiappan A, Rotzschke O, Wong HC, Marti HP, Chang A, Bigliardi-Qi M, Wang DY and Bigliardi PL: Evaluation of the applicability of the Immuno-solid-phase allergen chip (ISAC) assay in atopic patients in Singapore. Clinical and Translational Allergy, 2015, 5:9 42 Jing Hui Yik, Sandeep Jacob Sebastin, Lingaraj Krishna, Bigliardi PL: Pyoderma Gangrenosum Mimicking Early Acute Infection Following Total Knee Arthroplasty. Annals Acad Med Singapore, accepted for publication 10.2014 (publication April 2015). 43 Bigliardi-Qi M and Bigliardi PL: Review article - The role of opioid receptors in wound healing. Submitted to Receptors and Clinical Investigation, 08.2014 44 Ford S, Sardella T, Urich A, Burton NC, Kacprowicz M, Bigliardi M, Olivo M, Bigliardi PL and Razansky D. Structural and functional analysis of intact hair follicles and pilosebaceous units by volumetric multispectral optoacoustic tomography. Submitted to J Invest Dermatol, 11. 2014 (JID-2014-1036) 45 Dancik Y, Bigliardi PL, Bigliardi-Qi M and Jaworska J: Integrating dermal exposure scenarios in developmental and reproductive toxicity studies. Submitted to Reproductive Toxicology 11.2014 46 Gopu S, Bigliardi PL & Bigliardi-Qi M:Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Submitted to European J Cell Biol, 04. 2015 Book chapters 1 Itch: Basic Mechanisms and Therapy. Edited by Yosipovitch G, Greaves MV, Fleischer AB, McGlone F. Chapter 10 “Peripheral Opiate Receptor System in Human Epidermis and Itch “ by Bigliardi-Qi M and Bigliardi PL; pages 97-107 in Marcel Dekker, Inc., New York, Basel, January, 2004 2 Itch: Mechanisms and Treatment. Edited by Carstens E and Akiyama T:Chapter “Peripheral Opioids“ by Bigliardi PL and Bigliardi-Qi M. Series title “Frontiers in Neuroscience”, Taylor & Francis Group, London, 2014 Patent filings
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    7 1 USE OFSELECTIVE DELTA-OPIOID RECEPTOR MODIFIERS AND SPECIFIC SENSORY RECEPTOR LIGANDS. Inventors: Bigliardi-Qi M and Bigliardi PL. Pending patent (PCP filed 02.2014; No PCT/SG2014/000025) 2 Multi-spectral calibrated light source for long term cell culture study. Inventors: Paul Lorenz BIGLIARDI (IMB); CHUA Soo Jin (NUS; IMRE); TAY Chuan Beng (NUS); WANG Ben Zhong (IMRE); Mei BIGLIARDI-QI (IMB); Institutions: IMB, IMRE, NUS, Provisional SG Patent application filed 6.3.2015; Application No: 10201501747P 3 SUBMITTED: Co-Culture Device With Self-Refilling Of Culture Media Inventors: Wu Ruige; Seah Yen Peng Daphne; Wang Zhiping; Paul Lorenz Bigliardi (IMB); Mei Bigliardi-Qi (IMB); Viknish Krishnan Kutty (IMB). ETPL Ref: SIM/Z/08863; SIMTech Ref: rgwu-688 4 SUBMITTED: Thin Film Deposited Inorganic Metal Oxide as a Selective Substrate for Mammalian Cell Culture Inventors: Dykas Michal Marcin, Poddar Kingshuk, Thirumalai Venky Venkatesan, Krishnan Kutty Viknish, Bigliardi Paul, Bigliardi Mei. NUS Ref.