KEYWORDS

Cancer Epigenetics

Molecular Pathology

uropathology

Biobank

BIO

Prof. Carmen Jerónimo is Invited Associate Professor in Pathology and Molecular Genetics and the Director of the Master Course in Oncology at the University of Porto, as well as Group Leader of the Cancer Epigenetics Group at the Portuguese Oncology Institute of Porto (IPO Porto), Portugal.

She obtained her BSc in Biology (1994), MSc in Oncology (1998), PhD in Biomedical Sciences (2001) and Habilitation in Pathology and Molecular Genetics (2011) at the University of Porto.

She performed her PhD project at Johns Hopkins University (JHU) School of Medicine, Baltimore, MD, USA under the GABBA Programme, working on prostate cancer genetic and epigenetic alterations.

From 2002 until 2007, she was a Post-doctoral Fellow and Invited researcher at IPO Porto, in collaboration with JHU, working on detection of neoplastic cells by DNA-based technology in clinical samples obtained from non-invasive or minimal invasive methods.

In 2008 she established her independent group at IPO Porto, working on Cancer Biology and Epigenetics (FCT-2008 Science Program).

Her research interests are focused on the characterization of the epigenome of tumor cells, as well as the identification of functional changes involved in the breakdown of cell epigenetic homeostasis. In the context of Personalized Medicine, she is especially interested in the development of new of cancer epigenetic biomarkers based in liquid biopsies as well as in the drug discovery for cancer based on the modulation of cancer-related epigenetic aberrations. Owing to the relevance that Immuno-oncology has demonstrated in recent years, she is also investigating the epigenetic modulation of expression of biomolecules involved in immune checkpoint regulation, aiming at the improvement of immunotherapeutic strategies by combination with epi-drugs. More recently, she started tackling the contribution of deregulated non-coding RNAs expression and its interaction with other epigenetic mechanisms that may induce/promote malignant transformation.

She has supervised 3 PhD students and co-supervised 5 PhD students, as well as supervised 27 master students and several undergraduate students. Presently she mentors 2 Post-doctoral fellows, 3 PhD students, and 4 Master students. As scientific leader, She has collaborated in a patent submission (Methods and biomarkers for detection of bladder cancer US 20130210011/ EP 2630261 A1/ WO 2012052844 A1), based in a study from a collaboration with the Norwegian Radium Hospital and has participated in international projects funded by European Commission, within the Seventh Framework Programme (EpiDiaCan) and several nationally wide funded projects (FCT, Calouste Gulbenkian Foundation and LPCC-NRN). She has authored or co-authored more than 160 international scientific publications including four book chapters and several review articles and she serve as Section Editor of Clinical Epigenetics and Associate Editor of International Journal of Molecular Sciences and BMC Cancer.

She was MC substitute member of Action TD0905 (CMST) – Epigenetics: Bench to Bedside and presently she is MC member and Chair of Working group WG2 of COST Action CM1406 (CMST) – Epigenetic Chemical Biology (EPICHEM) and MC member of COST Action European Epitranscriptomics Network- CA16120-EPITRAN.

KNOW-HOW

-Quantitative methylation specifi PCR

-Bisulfite sequencing,

-Analysis of histone marks in a cellular context (IHC, WB, ChiP),

-In Vitro phenotypic Assyas: in vitro proliferation (MTT), apoptosis, Invasion, and wound healing and pharmacological assays,

-In vitro systems for genetic alterations: siRNA, shRNA, crispr/cas9 technology, genetic transfection,

-Tumor and bodily fluids banking.

KEY PUBLICATIONS

1.       Jerónimo C, Nomoto S, Caballero O, Usadel H, Henrique R, Varzim G, Oliveira J, Lopes C, Fliss M, Sidransky D. Mitochondrial mutations in early stage prostate cancer and bodily fluids. Oncogene 20 (37): 5195-5198, 2001.

2.       Jerónimo C, Usadel H, Henrique R, Oliveira J, Lopes C, Nelson WG, Sidransky D. Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ confined prostate adenocarcinoma. J Natl Cancer Inst 93(22): 1747-52, 2001.

3.       Jerónimo C, Costa I, Martins MC, Monteiro P, Lisboa S, Sousa CP, Henrique R, Teixeira MR, Lopes C. Detection of gene promoter hypermethylation in fine needle washings from breast lesions. Clin Cancer Res 9 (9): 3413-3417, 2003.

4.       Jerónimo C*, Henrique R*, Hoque MO, Ribeiro FR, Oliveira J, Fonseca D, Teixeira MR, Lopes C, Sidransky D. Quantitative RARβ2 hypermethylation: a promising prostate cancer marker. Clin Cancer Research 10(12): 4010-4014, 2004 (*Joint first authors).

5.       Hoque MO, Begum S, Topaloglu O, Jerónimo C, Mambo E, Westra WH, Califano III JA, Sidransky D. Detection of promoter hypermethylation of multiple genes in the tumor, urine and serum of patients with renal cancer. Cancer Res 64(15): 5511-7, 2004.

6.       Jerónimo C*, Henrique R*, Hoque MO, Mambo E, Ribeiro FR, Varzim G, Oliveira J, Teixeira MR, Lopes C, Sidransky D. A quantitative promoter methylation profile of prostate cancer. Clin Cancer Res 10(24): 8472-8478, 2004 (*Joint first authors).

7.       Henrique R*, Jerónimo C*, Teixeira MR, Hoque MO, Carvalho AL, Pais I, Ribeiro FR, Oliveira J, Lopes C, Sidransky D. Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues for clonal progression in prostate carcinogenesis. Mol Cancer Res 4(1):1-8, 2006, (*Joint first authors).

8.       Ribeiro FR, Jerónimo C, Henrique R, Fonseca D, Oliveira J, Lothe RA, Teixeira MR. 8q gain is an independent predictor of poor survival in diagnostic needle biopsies from prostate cancer suspects. Clin Cancer Res 12(13):3961-70, 2006.

9.       Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, Wood T, Jerónimo C, Rosenbaum E, Stern J, Yu M, Trink B, Kiviat NB, Sidransky D. Detection of Aberrant Methylation of Four Genes in Plasma DNA for the Detection of Breast Cancer. J Clin Oncol 24: 24(26): 4262-9, 2006.

10.   Ribeiro FR, Henrique R, Hektoen M, Berg M, Jerónimo C, Teixeira MR, Lothe RA. Genomic profiling of primary prostate carcinomas: novel amplified loci, recurrent regions of homozygous deletion, and methodological considerations regarding automated array-CGH scoring approaches. Mol Cancer, 5: 33, 2006.

11.   Carvalho AL, Chuang A, Jiang WW, Lee J, Begum S, Poeta L, Zhao M, Jerónimo C, Henrique R, Nayak CS, Park HML, Brait MRO, Liu C, Zhou S, Koch W, Fazio VM, Ratovitski E, Trink B, Sidransky D, Moon C, Califano JA.  DCC is a putative conditional tumor suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma. Cancer Res 66(19):9401-9406, 2006.

12.   Ribeiro FR, Henrique R, Martins AT, Jerónimo C, Teixeira MR. Relative copy number gain of MYC in diagnostic needle biopsies is an independent prognostic factor in prostate cancer patients. Eur Urol 52(1):116-25, 2007.

13.   Henrique R, Ribeiro FR, Fonseca D, Hoque MO, Carvalho AL, Costa VL, Pinto M, Oliveira J, Teixeira MR, Sidransky D, Jerónimo C. High Promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin Cancer Res 13(20):6122 -6129, 2007.

14.   Carvalho AL, Jeronimo C, Kim MM, Henrique R, Zhang Z, Hoque MO, Chang S, Brait M, Nayak CS, Jiang WW, Claybourne Q, Tokumaru Y, Lee J, Goldenberg D, Garrett-Mayer E, Goodman S, Moon CS, Koch W, Westra WH, Sidransky D, Califano JA. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin Cancer Res 14(1):97-107, 2008.

15.   Hoque MO, Kim MS, Ostrow KL, Liu J, Wisman GB, Park HL, Poeta ML, Jeronimo C, Henrique R, Lendvai A, Schuuring E, Begum S, Rosenbaum E, Ongenaert M, Yamashita K, Califano J, Westra W, van der Zee AG, Van Criekinge W, Sidransky D. Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res 68(8):2661-70, 2008.

16.   Costa VL, Henrique R, Ribeiro FR, Carvalho JR, Oliveira J, Lobo F. Teixeira MR, Jerónimo C. Epigenetic regulation of Wnt-signaling pathway in urological tumors. Epigenetics 16;5(4):343-51, 2010.

17.   Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, Rodrigues A, Magalhães JS, Oliveira J, Lothe RA, Teixeira MR, Jeronimo C*, Lind GE*.Three epigenetic biomarkers, GDF15, TMEFF2 and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin Cancer Res 16(23):5842-51, 2010 (*Joint senior authors).

18.   Duarte-Pereira S, Paiva F, Costa VL, Ramalho-Carvalho J, Savva-Bordalo J, Rodrigues A, Ribeiro FR, Silva VM, Oliveira J, Henrique R, Jerónimo C. Prognostic value of opioid binding protein/cell adhesion molecule-like promoter methylation in bladder carcinoma. Eur J Cancer 47(7):1106-14, 2011.

19.   Carvalho AL, Henrique R, Jeronimo C, Nayak C, Reddy A, Hoque MO, Chang SS, Brait M, Claybourne Q, Goldenberg DM, Khan Z, Khan T, Westra WH, Sidransky D, Koch WM, Califano JA. Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clin Cancer Res 17(14):4782-9, 2011.

20.   Martins AT, Monteiro P, Ramalho-Carvalho J, Costa VL, Dinis-Ribeiro M, Leal C, Henrique R, Jerónimo C. High RASSF1A promoter methylation levels are predictive of poor prognosis in fine-needle aspirate washings of breast cancer lesions. Breast Cancer Res Treat 129(1):1-9, 2011.

21.   Costa VL, Henrique R, Danielsen SA, Eknaes M, Skotheim RI, Patrício P, Morais A, Oliveira J, Lothe RA, Teixeira MR, Lind GE, Jeronimo C. TCF21 and PCDH17 methylation: an innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics 6 (9):1-11, 2011.

22.   Sousa EJ, Graça I, Baptista T, Vieira FQ, Palmeira C, Henrique R, Jerónimo C. Enoxacin inhibits growth of prostate cancer cells and effectively restores microRNA processing. Epigenetics 8(5):548-58, 2013.

23.   Jin Y, Qu S, Tesikova M, Wang L, Kristian A, Mælandsmo GM, Kong H, Zhang T, Jerónimo C, Teixeira MR, Yuca E, Tekedereli I, Gorgulu K, Alpay N, Sood AK, Lopez-Berestein G, Danielsen HE, Ozpolat B, Saatcioglu F. Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer. Proc Natl Acad Sci U S A. 110(28):E2572-81, 2013.

24.   Baptista T, Graça I, Sousa EJ, Oliveira AI, Costa NR, Costa-Pinheiro P, Amado F, Henrique R, Jerónimo C. Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer. Oncotarget. 4(10):1673-85, 2013.

25.   Silva-Santos RM, Costa-Pinheiro P, Luis A, Antunes L, Lobo F, Oliveira J, Henrique R, Jerónimo C. MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Br J Cancer. 109(10):2646-53, 2013.

26.   Henrique R, Oliveira AI, Costa VL, Baptista T, Martins AT, Morais A, Oliveira J, Jerónimo C. Epigenetic regulation of MDR1 gene through post-translational histone modifications in prostate cancer. BMC Genomics. 14: 898, 2013.

27.   Monteiro-Reis S, Leça L, Almeida M, Antunes L, Monteiro P, Dias PC, Morais A, Oliveira J, Henrique R, Jerónimo C. Accurate detection of upper tract urothelial carcinoma in tissue and urine by means of quantitative GDF15, TMEFF2 and VIM promoter methylation. Eur J Cancer 50(1):226-33, 2014.

28.   Vieira FQ, Costa-Pinheiro P, Ramalho-Carvalho J, Pereira A, Menezes FD, Antunes L, Carneiro I, Oliveira J, Henrique R, Jeronimo C. Deregulated expression of selected histone methylases and demethylases in prostate carcinoma. Endocr Relat Cancer 16;21(1):51-61, 2014.

29.   Graça I, Sousa EJ, Costa-Pinheiro P, Vieira FQ, Torres-Ferreira J, Martins MG, Henrique R, Jerónimo C. Anti-neoplastic properties of hydralazine in prostate cancer. Oncotarget. 5(15): 5950-64, 2014.

30.   Chen LM, Chang M, Dai Y, Chai KX, Dyrskjøt L, Sanchez-Cabayo M, Szarvas T, Zwarthoff EC, Lokeswhar V, Jeronimo C, Parker AS, Ross S, Borre M, Orntoft TF, Jaeger T, Beukers W, Lopez LE, Henrique R, Young PR, Urquidi V, Goodison S, Rosser CJ. External Validation of a Multiplex Urinary Protein Panel for the Detection of Bladder Cancer in a Multicenter Cohort. Cancer Epidemiol Biomarkers Prev 23(9):1804-12, 2014.

31.   Costa-Pinheiro P, Quintela Vieira F, Ramalho-Carvalho J, Torres-Ferreira J, Gonçalves CS, Costa BM, Oliveira J, Henrique R, Jeronimo C. MicroRNA-375 plays a dual role in prostate carcinogenesis, Clinical Epigenetics 7:42, 2015.

32.   Vieira FQ, Costa-Pinheiro P, Almeida-Rios D., Graça I, Monteiro-Reis S, Simões-Sousa S, Carneiro I, Sousa EJ, Godinho MI, Baltazar F, Henrique R, Jerónimo C. SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3. Oncotarget 6(15):13644-57, 2015.

33.   Junqueira-Neto S, Vieira FQ, Montezuma D, Costa NR, Antunes L, Baptista T, Oliveira AI, Graça I, Rodrigues A, Magalhães JS, Oliveira J, Henrique R, Jerónimo C. Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder. Mol Carcinog. 54(7):523-31, 2015.

34.   Bartosch C, Monteiro-Reis S, Almeida-Rios D, Vieira R, Castro A, Moutinho M, Rodrigues M, Graça I, Lopes JM, Jerónimo C. Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium. Oncotarget 12;7(2):1144-54, 2016.

35.   Almeida-Rios D, Graça I, Vieira FQ, Ramalho-Carvalho J, Pereira-Silva E, Martins AT, Oliveira J, Gonçalves CS, Costa BM, Henrique R, Jerónimo C. Histone methyltransferase PRMT6 plays an oncogenic role of in prostate cancer. Oncotarget 16;7(33):53018-53028, 2016.

36.   Ramalho-Carvalho J, Martins JB, Cekaite L, Sveen A, Torres-Ferreira J, Graça I, Costa-Pinheiro P, Eilertsen IA, Antunes L, Oliveira J, Lothe RA, Henrique R, Jerónimo C. Epigenetic disruption of miR-130a promotes prostate cancer by targeting SEC23B and DEPDC1. Cancer Lett 385:150-159, 2017.

37.   Padrão NA, Monteiro-Reis S, Torres-Ferreira J, Antunes L, Leça L, Montezuma D, Ramalho-Carvalho J, Dias PC, Monteiro P, Oliveira J, Henrique R, Jerónimo C. MicroRNA promoter methylation: a new tool for accurate detection of urothelial carcinoma. Br J Cancer 116(5):634-639, 2017.

38.   Torres-Ferreira J, Ramalho-Carvalho J, Gomez A, Menezes FD, Freitas R, Oliveira J, Antunes L, Bento MJ, Esteller M, Henrique R, Jerónimo C. MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors. Mol Cancer 16(1):26, 2017.

39.   Ramalho-Carvalho J, Graça I, Gomez A, Oliveira J, Henrique R, Esteller M, Jerónimo C. Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer. J Hematol Oncol 10(1):43, 2017.

40.   Monteiro FL, Vitorino R, Wang J, Cardoso H, Laranjeira H, Simões J, Caldas M, Henrique R, Amado F, Williams C, Jerónimo C, Helguero LA. The histone H2A isoform Hist2h2ac is a novel regulator of proliferation and epithelial-mesenchymal transition in mammary epithelial and in breast cancer cells. Cancer Lett 396:42-52, 2017

41.   Barros-Silva D, Costa-Pinheiro P, Duarte H, Sousa EJ, Evangelista AF, Graça I, Carneiro I, Martins AT, Oliveira J, Carvalho AL, Marques MM, Henrique R, Jerónimo C. MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis. Cell Death Dis 9(2):167, 2018.

42.   Vilela-Salgueiro B, Barros-Silva D, Lobo J, Costa AL, Guimarães R, Cantante M, Lopes P, Braga I, Oliveira J, Henrique R, Jerónimo C. Germ cell tumour subtypes display differential expression of microRNA371a-3p. Philos Trans R Soc Lond B Biol Sci. 373(1748), 2018.

43.   Schrijver W, Schuurman K, van Rossum A, Droog M, Jeronimo C, Salta S, Henrique R, Wesseling J, Moelans C, Linn SC, van den Heuvel M, van Diest P, Zwart W. FOXA1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome. Mol Oncol. 12(11):1884-1894, 2018.

44.   Lobo J, Costa AL, Vilela-Salgueiro B, Rodrigues Â, Guimarães R, Cantante M, Lopes P, Antunes L, Jerónimo C, Henrique R. Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists. Hum Pathol. pii: S0046-8177 (18) 30283-1, 2018.

45.   Nunes SP, Moreira-Barbosa C, Salta S, Palma de Sousa S, Pousa I, Oliveira J, Soares M, Rego L, Dias T, Rodrigues J, Antunes L, Henrique R, Jerónimo C. Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women. Cancers 10(10). pii: E357, 2018.

46.   Moreira-Barbosa C, Barros-Silva D, Costa-Pinheiro P, Torres-Ferreira J, Constâncio V, Freitas R, Oliveira J, Antunes L, Henrique R, Jerónimo C. Comparing diagnostic and prognostic performance of two-gene promoter methylation panels in tissue biopsies and urines of prostate cancer patients. Clin Epigenetics. 10(1):132, 2018.

47.   Salta S, Nunes SP, Fontes-Sousa M, Lopes P, Freitas M, Caldas M, Antunes L, Castro F, Antunes P, Palma de Sousa S, Henrique R, Jerónimo C. A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA. J Clin Med. 7;7(11). pii: E420, 2018.

48.   Costa AL, Moreira-Barbosa C, Lobo J, Vilela-Salgueiro B, Cantante M, Guimarães R, Lopes P, Braga I, Oliveira J, Antunes L, Henrique R, Jerónimo C. DNA methylation profiling as a tool for testicular germ cell tumors subtyping. Epigenomics. 10(12):1511-1523, 2018.

49.   Stelloo S, Nevedomskaya E, Kim Y, Schuurman K, Valle-Encinas E, Lobo J, Krijgsman O, Peeper DS, Chang SL, Feng FY, Wessels LFA, Henrique R, Jerónimo C, Bergman AM, Zwart W. Integrative epigenetic taxonomy of primary prostate cancer. Nat Commun. 9(1):4900, 2018.

50.   Lobo J, Costa AL, Cantante M, Guimarães R, Lopes P, Antunes L, Braga I, Oliveira J, Pelizzola M, Henrique R, Jerónimo C.m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance. J Transl Med. 2019 Mar 12;17(1):79, 2019.

 

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