Ipatimup

Name: Leonor David

E-mail: ldavid@ipatimup.pt

Leonor David

Member of

Researcher of Differentiation and cancer

Short CV

Leonor David was born in Porto, Portugal, in 1955. Leonor David is a Pathologist and Full Professor of Pathology at the Medical Faculty of Porto, Porto, Portugal. She received a degree in medicine and earned her Ph.D. degree from the Medical Faculty of Porto, Portugal, in 1979 and 1993, respectively. She did part of her Ph.D. and postdoctoral research at the Radium Hospital in Oslo, Norway and at the University of Copenhagen, Denmark. Her main interest is focused on mucins and mucin glycosylation in gastric carcinogenesis. She is also particularly interested in the regulation of events leading to intestinal metaplasia. Leonor David participated in the organizing committee of several international meetings on cancer and mucin/mucin glycosylation, published over 100 papers in journals with peer-review, wrote 6 book chapters, is Member of the Council of the European Association for Cancer Research. Leonor David is president of ASPIC (Portuguese Association for Cancer Research).

Highlights

Characterization and regulation of mucin glycosylation in carcinogenesis processes using different approaches, from glycopeptide characterization using Proximity Ligation Assays (PLA), to zinc-finger strategies to manipulate CDX2 dependent glycoproteome modifications, to classical approaches like luciferase assays, ChIP assays and immunofluorescence. Recently I have focused on the study of MUC16 mucin and its glycoforms in different cancer models, on production and characterization of MUC16 monoclonal antibodies and in dissecting the role of MUC16-mesothelin interaction in cancer progression.

Supervisor of

Lara Marcos da Silva, Visiting Researcher

Luísa Melo, Project Manager

Mariana Nunes, Master Student (thesis)

Nuno Teixeira Marcos, Lab Manager

Ricardo Coelho, PhD Student

Sara Ricardo, Junior Researcher

PI (running)

"Bloqueio da interacção MUC16-mesotelina para inibir a metastização peritoneal do carcinoma do ovário"

PI (closed)

"Mucin MUC16 - CA125 cancer biomarker - biological functions and development of new biomarker assays"

Differentiation in cancer with emphasis on glycoproteome alterations

"MUC1 mucin transcriptional regulation by the maternal hormones progesterone and oestrogen and by the embryo in bovine endometrium cells - a crucial process on implantation"

"Manutenção, caracterização e comercialização dos anticorpos monoclonais para mucinas"

"Discovery of novel cancer serum biomarkers based on aberrant post translational modifications of O-glycoproteins (O-PTM-Biomarkers) and their application to early detection of cancer"

Secretor and Lewis phenotypes/genotypes in Helicobacter pylori and calicivirus infection

"Genes associated to intestinal metaplasia of the gastric mucosa (MUC2 mucin and fucosyltransferase FUT3): regulation of transcription and role in Helicobacter pylori adhesion."

"Caracterização de factores biológicos e estilos de vida com impacto de ocorrência e na forma de apresentação do cancro – Lesões da mucosa gástrica em Moçambique e Portugal: o enigma Africano"

First Author

1. David L, Silva F, Seruca R, Pinto M, Reis C, Sobrinho-Simões M

Correspondence re: A. E. Biemer-Huttmann et al., Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis. Clin. Cancer Res., 6: 1909-1916, 2000. Clinical cancer research : an official journal of the American Association for Cancer Research 6: 4461-2, 2000. [Letter]

PMID: 11106267.

4.6

2. David L, Sobrinho Simões M

Tenascin and oncofetal fibronectin--oncofetal markers or indicators of extracellular matrix remodelling? British journal of cancer 74: 990-1, 1996. [Letter]

PMID: 8826873.

3. David L, Nesland JM, Holm R, Sobrinho-Simões M

Expression of laminin, collagen IV, fibronectin, and type IV collagenase in gastric carcinoma. An immunohistochemical study of 87 patients. Cancer 73: 518-27, 1994. [Article]

PMID: 8299074.

4. David L, Mandel U, Clausen H, Sobrinho-Simões M

Immunohistochemical expression of oncofetal fibronectin in benign and malignant lesions of the stomach. European journal of cancer (Oxford, England : 1990) 29A: 2070-1, 1993. [Letter]

PMID: 8280503.

5. David L, Nesland JM, Funderud S, Sobrinho-Simões M

CDw75 antigen expression in human gastric carcinoma and adjacent mucosa. Cancer 72: 1522-7, 1993. [Article]

PMID: 8348485.

Senior Author

1. Coelho R, Marcos-Silva L, Ricardo S, Ponte F, Costa A, Lopes JM, David L

Peritoneal dissemination of ovarian cancer: role of MUC16-mesothelin interaction and implications for treatment. Expert review of anticancer therapy 18: 177-186, 2018. [Review]

doi: 10.1080/14737140.2018.1418326 PMID: 29241375.

2.3 (*)

2. Ricardo S, Marcos-Silva L, Valente C, Coelho R, Gomes R, David L

Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors. Virchows Archiv : an international journal of pathology 468: 715-22, 2016. [Article]

doi: 10.1007/s00428-016-1929-6 PMID: 27003157.

2.8

3. Ricardo S, Marcos-Silva L, David L

Mucin carriers of TF in ovarian cancer. Journal of cancer research and clinical oncology 142: 1867-8, 2016. [Letter]

doi: 10.1007/s00432-016-2186-4 PMID: 27277091.

3.5

4. Ricardo S, Marcos-Silva L, Pereira D, Pinto R, Almeida R, Söderberg O, Mandel U, Clausen H, Felix A, Lunet N, David L

Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours. Molecular oncology 9: 503-12, 2015. [Article]

doi: 10.1016/j.molonc.2014.10.005 PMID: 25454345.

5.4

5. Pinto R, Barros R, Pereira-Castro I, Mesquita P, da Costa LT, Bennett EP, Almeida R, David L

CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia. Laboratory investigation; a journal of technical methods and pathology 95: 718-27, 2015. [Article]

doi: 10.1038/labinvest.2015.52 PMID: 25867765.

4.2

6. Silva ML, Gutiérrez E, Rodríguez JA, Gomes C, David L

Construction and validation of a Sambucus nigra biosensor for cancer-associated STn antigen. Biosensors & bioelectronics 57: 254-61, 2014. [Article]

doi: 10.1016/j.bios.2014.02.006 PMID: 24594592.

6.4

7. Carrilho C, Gouveia P, Yokohama H, Lopes JM, Lunet N, Ferro J, Ismail M, Walboomers J, Sobrinho-Simões M, David L

Human papillomaviruses in intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva: a study from Mozambique. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 22: 566-8, 2013. [Article]

doi: 10.1097/CEJ.0b013e328363005d PMID: 23752127.

2.8

8. Pinto R, Carvalho AS, Conze T, Magalhães A, Picco G, Burchell JM, Taylor-Papadimitriou J, Reis CA, Almeida R, Mandel U, Clausen H, Söderberg O, David L

Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation. Journal of cellular and molecular medicine 16: 1474-84, 2012. [Article]

doi: 10.1111/j.1582-4934.2011.01436.x PMID: 21883895.

4.8

9. Reis CA, Osorio H, Silva L, Gomes C, David L

Alterations in glycosylation as biomarkers for cancer detection. Journal of clinical pathology 63: 322-9, 2010. [Review]

doi: 10.1136/jcp.2009.071035 PMID: 20354203.

231

2.5

10. Silva LM, Carvalho AS, Guillon P, Seixas S, Azevedo M, Almeida R, Ruvoën-Clouet N, Reis CA, Le Pendu J, Rocha J, David L

Infection-associated FUT2 (Fucosyltransferase 2) genetic variation and impact on functionality assessed by in vivo studies. Glycoconjugate journal 27: 61-8, 2010. [Article]

doi: 10.1007/s10719-009-9255-8 PMID: 19757028.

2.7

11. Azevedo M, Eriksson S, Mendes N, Serpa J, Figueiredo C, Resende LP, Ruvoën-Clouet N, Haas R, Borén T, Le Pendu J, David L

Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype. The Journal of pathology 215: 308-16, 2008. [Article]

doi: 10.1002/path.2363 PMID: 18498114.

5.1

12. Serpa J, Mesquita P, Mendes N, Oliveira C, Almeida R, Santos-Silva F, Reis CA, LePendu J, David L

Expression of Lea in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation. Cancer letters 242: 191-7, 2006. [Article]

doi: 10.1016/j.canlet.2005.11.009 PMID: 16427187.

3.3

13. Pinto de Sousa J, David L

Role of immunohistochemical expression of MUC5B in gastric carcinoma. In: Handbook of immunohistochemistry and in situ hybridization of human carcinomas. Handbook of immunohistochemistry and in situ hybridization of human carcinomas 4 4: 191-194, 2006. []

14. Mesquita P, Raquel A, Nuno L, Reis CA, Silva LF, Serpa J, Van Seuningen I, Barros H, David L

Metaplasia--a transdifferentiation process that facilitates cancer development: the model of gastric intestinal metaplasia. Critical reviews in oncogenesis 12: 3-26, 2006. []

PMID: 17078204.

3.4 (*)

15. Almeida R, Almeida J, Shoshkes M, Mendes N, Mesquita P, Silva E, Van Seuningen I, Reis CA, Santos-Silva F, David L

OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells. The Journal of pathology 207: 396-401, 2005. [Article]

doi: 10.1002/path.1861 PMID: 16278805.

6.2

16. Carrilho C, Cirnes L, Alberto M, Buane L, Mendes N, David L

Distribution of HPV infection and tumour markers in cervical intraepithelial neoplasia from cone biopsies of Mozambican women. Journal of clinical pathology 58: 61-8, 2005. [Article]

doi: 10.1136/jcp.2004.020552 PMID: 15623485.

2.2

17. Carrilho C, Alberto M, Buane L, David L

Keratins 8, 10, 13, and 17 are useful markers in the diagnosis of human cervix carcinomas. Human pathology 35: 546-51, 2004. [Article]

PMID: 15138927.

3.4

18. Serpa J, Mendes N, Reis CA, Santos Silva LF, Almeida R, Le Pendu J, David L

Two new FUT2 (fucosyltransferase 2 gene) missense polymorphisms, 739G-->A and 839T-->C, are partly responsible for non-secretor status in a Caucasian population from Northern Portugal. The Biochemical journal 383: 469-74, 2004. [Article]

doi: 10.1042/BJ20040803 PMID: 15250822.

4.3

19. Mesquita P, Almeida R, Van Seuningen I, David L

Coordinated expression of MUC2 and CDX-2 in mucinous carcinomas of the lung can be explained by the role of CDX-2 as transcriptional regulator of MUC2. The American journal of surgical pathology 28: 1254-5, 2004. [Letter]

PMID: 15316331.

4.7

20. Reis CA, Teixeira A, David L

Role of mucins in Helicobacter pylori adhesion to the gastric mucosa. Helicobacter 9: 181; author reply 181-2, 2004. [Letter]

doi: 10.1111/j.1083-4389.2004.00216.x PMID: 15068421.

2.3

21. Serpa J, Lunet N, Mendes N, Barros H, David L

Lewis and Secretor status and Helicobacter pylori eradication. Epidemiology and infection 132: 997-8; author reply 998-9, 2004. [Letter]

PMID: 15473165.

1.6

22. Almeida R, Silva E, Santos-Silva F, Silberg DG, Wang J, De Bolós C, David L

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. The Journal of pathology 199: 36-40, 2003. [Article]

doi: 10.1002/path.1246 PMID: 12474224.

205

4.9

23. Mesquita P, Jonckheere N, Almeida R, Ducourouble MP, Serpa J, Silva E, Pigny P, Silva FS, Reis C, Silberg D, Van Seuningen I, David L

Human MUC2 mucin gene is transcriptionally regulated by Cdx homeodomain proteins in gastrointestinal carcinoma cell lines. The Journal of biological chemistry 278: 51549-56, 2003. [Article]

doi: 10.1074/jbc.M309019200 PMID: 14525978.

106

6.5

24. Simpson RH, Prasad AR, Lewis JE, Skálová A, David L

Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases. The American journal of surgical pathology 27: 1070-9, 2003. [Article]

PMID: 12883239.

4.5

25. Mesquita P, Peixoto AJ, Seruca R, Hanski C, Almeida R, Silva F, Reis C, David L

Role of site-specific promoter hypomethylation in aberrant MUC2 mucin expression in mucinous gastric carcinomas. Cancer letters 189: 129-36, 2003. [Article]

PMID: 12490305.

2.6

26. Silva F, Carvalho F, Peixoto A, Teixeira A, Almeida R, Reis C, Bravo LE, Realpe L, Correa P, David L

MUC1 polymorphism confers increased risk for intestinal metaplasia in a Colombian population with chronic gastritis. European journal of human genetics : EJHG 11: 380-4, 2003. [Article]

doi: 10.1038/sj.ejhg.5200978 PMID: 12734543.

3.7

27. Carrilho C, Gouveia P, Cantel M, Alberto M, Buane L, David L

Characterization of human papillomavirus infection, P53 and Ki-67 expression in cervix cancer of Mozambican women. Pathology, research and practice 199: 303-11, 2003. [Article]

PMID: 12908520.

0.8

28. Serpa J, Almeida R, Oliveira C, Silva FS, Silva E, Reis C, Le Pendu J, Oliveira G, Ribeiro LM, David L

Lewis enzyme (alpha1-3/4 fucosyltransferase) polymorphisms do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population. Journal of human genetics 48: 183-9, 2003. [Article]

doi: 10.1007/s10038-003-0007-5 PMID: 12730721.

2.3

29. Silva F, Carvalho F, Peixoto A, Seixas M, Almeida R, Carneiro F, Mesquita P, Figueiredo C, Nogueira C, Swallow DM, Amorim A, David L

MUC1 gene polymorphism in the gastric carcinogenesis pathway. European journal of human genetics : EJHG 9: 548-52, 2001. [Article]

doi: 10.1038/sj.ejhg.5200677 PMID: 11464247.

3.2

30. Carrilho C, Cantel M, Gouveia P, David L

Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix. Virchows Archiv : an international journal of pathology 437: 173-9, 2000. [Article]

PMID: 10993278.

1.7

31. Garcia E, Carvalho F, Amorim A, David L

MUC6 gene polymorphism in healthy individuals and in gastric cancer patients from northern Portugal. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 6: 1071-4, 1997. [Article]

PMID: 9419405.

32. Marinho A, Moura A, Baptista M, Macedo G, Pimenta A, David L

Granular cell tumour and leiomyomatosis of the esophagus--a non-coincidental association? Pathology, research and practice 192: 492-5, 1996. [Article]

PMID: 8832756.

33. David L, Sobrinho Simões M

Tenascin and oncofetal fibronectin--oncofetal markers or indicators of extracellular matrix remodelling? British journal of cancer 74: 990-1, 1996. [Letter]

PMID: 8826873.