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Curriculum vitae

Jamel EDDOUZI, Ph.D. in Microbiology and Molecular Biology

* Laboratory of Biochemistry and Molecular Biology, Faculty of Sciences of Tunis, University of Tunis El-Manar, Tunis, Tunisia/ Institute of Microbiology, Lausanne University Hospital and University of Lausanne.

* Morris Park Ave (Apt2), Bronx, NY, USA, 10462.

Mobile: 530-***-****

Email: ad46il@r.postjobfree.com / ad46il@r.postjobfree.com Linkedin : www.linkedin.com/in/jamel-eddouzi

EDUCATION

University of Tunis ElManar, Tunis, Tunisia & Institute of Microbiology, University of Lausanne, Lausanne, Switzerland.

PhD, Microbiology and Molecular Biology 2009 – 2013

- Identification of Candida species associated with hospital infections in Tunisia.

- Molecular characterization of transcriptional regulatory networks involved in antifungal drug resistance in isolated species such as C. albicans and C. tropiclais using functional genomics approaches.

Supervisors: Dr. Mohamed Manai, Laboratory of Biochemistry and Molecular Biology, Faculty of Sciences of Tunis. &

Dr. Dominique Sanglard, Institute of Microbiology, Lausanne University Hospital and University of Lausanne.

University of Tunis ElManar, Institut Pasteur de Tunis (IPT).

Internship in Molecular Biology. A genetic approach to improve heterologous protein expression in Yarrowia lipolytica. (Student scholar in Biotechnology).

Supervisor: Dr. Hela Kallel, Yeast Molecular Biology unit. 2008

Faculty of Sciences of Tunis, University of Tunis ElManar, Tunis, Tunisia.

M.Sc., Microbiology 2005 – 2007

- Morphological and molecular characterization of Candida species associated with hospital infections in Tunisia.

- Biofilm formation and virulence properties of Candida spp. isolated from hospitalised patients in Tunisia.

Supervisors: Dr. Kacem Mahdouani and Dr. Kamel Chaieb, Laboratory of Bacteriology and Molecular Biology, Faculty of Pharmacy of Monastir. Faculty of Sciences of Tunis, University of Tunis ElManar, Tunis, Tunisia.

B.Sc., Life and Earth Sciences 2001 – 2005

RESEARCH EXPERIENCE

Visiting scholar, Department of Plant Pathology, University of California Davis_Eskalen Lab. 2023

- Identification, biology, epidemiology, and control of fungal and bacterial pathogens on vines, tree fruits, and small fruits.

- Fungicide efficacy trials using conventional and novel programs to treat various fungal diseases of wine grapes, apples, pears and other small fruit crops.

- Supervise and train the undergraduate and graduate students.

Supervisor: Dr. Akif Eskalen.

February –

July

Visiting scholar, Instituto de Ciencias de la Vid y del Vino. 2022

- Biology, ecology, and control of fungal pathogens of Mediterranean crops with emphasis on grapevine trunk diseases.

- Supervise and train the undergraduate and graduate students.

Supervisor: Dr. David Gramaje.

October –

December

Postdoctoral Scholar, Institut National de la Recherche Agronomique de Tunisie. 2020 – 2022

- Molecular tools for detection and identification of plant pathogenic agents.

- Supervise, train, discipline and evaluate the performance of laboratory staff and trainees.

Supervisor: Dr. Mohamed Rabeh Hajalaoui.

Teaching Assistant, Department of Biology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunisia.

2016 – 2019

- Biochemistry of cellular communication.

- Microbiological analysis methods.

- Microbiology and Molecular biology.

Postdoctoral Scholar, Faculty of Pharmacy and Laboratory of Medical and Molecular Biology, CHU Ibn Eljazzar, Kairouan, Tunisia.

2016 – 2019

- Supervise, train, discipline and evaluate the performance of laboratory staff and trainees. Page 2 of 5

- Direct and coordinate the daily operations of laboratories providing diagnostic services with special supervisory responsibilities during routine testing.

- Relationship between genetic polymorphisms of MnSOD and GPx1 and obesity risk in Tunisia population (research part).

- Relationship between Oxidative stress and Colorectal cancer (research part).

Supervisor: Dr. Kacem Mahdouani

Postdoctoral Scholar, Laboratory of Virology, College of Pharmacy, Chung-Ang University, Seoul, South Korea.

2014 – 2015

- Antibodies against HPV antigens as biomarker for early detection of cervical cancer/ ELISA was used to detect serum antibodies against three antigens (E6, E7 and L1) of three serotypes of HPV

(16, 18 and 58) (research part).

- Endogenous Retrovirus type K (HERV-K HML-2): A Potential Biomarker for early detection of breast cancer/ (HERV-K HML-2) env gene (research part).

- Direct and coordinate the daily operations of laboratories providing diagnostic services with special supervisory responsibilities during routine testing.

- Supervise, train, discipline and evaluate the performance of laboratory staff and trainees.

Supervisor: Dr. Hong-Jin Kim

Teaching Assistant, Department of Biology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunisia.

2013 – 2014

- Microbiological analysis methods

- Microbiology and Molecular biology.

TRAINING and SCIENTIFIC EVENTS

Post-Doc Innovation Program, South Mediterranean University, Tunis, Tunisia. Oct-Nov – 2021

TenStep EPM Tunisia (REF N 1774): Fundamentals of Project Management. April – 2014

First International Conference of Tunisian Association of Microbial Ecology: Microbial Diversity: Challenges and Applications, Hammamet, Tunisia. November – 2013

Laboratory Safety, Institute of microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.

February – 2011

The International Food Microbiology Seminar, Hammamet, Tunisia. March – 2009

The third scientific days of Tunisian Society of Microbiology, Monastir, Tunisia November – 2007 FELLOWSHIP and SUPERVISION ACTIVITIES

FUNDING AGENCY FUNDING DATE or PERIOD

MOBIDOC Postdoctoral Fellowship Program. 2018 – 2020

The National Research Foundation of Korea Postdoctoral Fellowship Program 2014 – 2015

MOBIDOC Postdoctoral Fellowship Program. Jan- June – 2014

Swiss Government Excellence PhD Scholarships for foreign students Program 2010 – 2012 Co-supervisor for B.Sc./M.Sc./PharmD. Students

Meriam BEN CHAABANE (M.Sc. student, Faculty of Sciences of Tunis). December – 2018

Rihab MOKNI (B.Sc. student, Higher Institute of Biotechnology of Monastir). May – 2017

Amal HAMZAOUI (B.Sc. student, Higher Institute of Biotechnology of Monastir). May – 2017

Dorra DRIDI (PharmD. student, Faculty of Pharmacy of Monastir). March – 2017

Meriem OUERTANI (PharmD. student, Faculty of Pharmacy of Monastir). February – 2017

Ahmed ALLANI (PharmD. student, Faculty of Pharmacy of Monastir). May – 2016 AREA of COMPETENCE

Biochemistry • Cell biology • Immunology • Microbiology • Molecular Biology • Lab Skills:

Gel electrophoresis • Western Blotting • Cell culture • SDS-PAGE • Staining and Detecting Electrophoresis Bands • Recombinant fusion proteins for affinity purification • MALDI-TOF MS • GC/MS • ELISA • Flow cytometry • Immunoprecipitation • Production of polyclonal antibodies • Isolation and Identification of Bacteria and Fungi • Antimicrobial and Antifungal Susceptibility Testing • Extraction and purification of DNA, RNA and Proteins • Enzyme digestion • PCR • PFGE • RFLP • qRT-PCR • Expression vector construction • Bacterial transformation and Plasmid purification • DNA sequencing • Molecular Docking • LANGUAGE

Arabic : Native speaker

English : Proficient

French : Fluent

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PUBLICATIONS

Djebali R, Eddouzi J, Sebei A, Chaabane R, Rezgui M, Bahrouni H, Medini Z, Bchini H. Behavior of three cereals cultivated in Tunisia under saline constraints and cationic homeostasis between sodium and potassium. Env.Wat. Sci. pub. H. Ter. Int. J.2020; 4 (4): 534-545. https://doi.org/10.48421/IMIST.PRSM/ewash-ti-v4i4.23416.

Tarchoune I, Sgherri C, Eddouzi J, Zinnai A, Quartacci MF and Zarrouk M. Olive Leaf Addition Increases Olive Oil Nutraceutical Properties. Molecules2019, 24, 545: https://doi.org/10.3390/molecules24030545.

Hajlaoui MR, Nouri MT, Hamrouni N, Trouillas FP, Ben Yahmed N, Eddouzi J, Mnari- Hattab M. First record of dieback and decline of plum caused by Neoscytalidium dimidiatum in Tunisia. NewDisease Reports(2018) 38, 20: http://dx.doi.org/10.5197/j.2044-0588.2018.038.020.

Jin Y, Choi JW, Kim HJ, Eddouzi J, Kim SC, Ju W, Kim YH, KimHJ. Profiling of serum antibodies against human papillomavirus antigens in Korean women with cervical intraepithelial neoplasia and cervical cancer.Cancer Med. 2018. (11):5655-5664: https://doi.org/10.1002/cam4.1810.

Dahmani A, Noumi E, Trabelsi I, Eddouzi J, Sanglard D, Del Campo R, Snoussi M. Extracellular enzymes and adhesive properties of medically important Candida spp. strains from landfill leachate. Microbial Pathogenesis.2017: https://doi.org/10.1016/j.micpath.2018.01.042.

Zammouri S, Eddouzi J, Zaagueri T, Belkhadhi MS, Hajlaoui MR and Mnari-Hattab M. First report of Tomato Leaf Curl New Delhi Virus on Tomato Crop in Tunisia. Journal of Plant Pathology. 2017: http://dx.doi.org/10.4454/jpp.v99i3.3975.

Eddouzi J, Lohberger A, Vogne C, Manai M, Sanglard D. Identification and antifungal susceptibility of a large collection of yeast strains isolated in Tunisian hospitals. Med Mycol.2013; 51(7):737-46: https://doi.org/10.3109/13693786.2013.800239.

Eddouzi J, Parker JE, Vale-Silva LA, Coste A, Ischer F, Kelly S, Manai M, Sanglard D. Molecular mechanisms of drug resistance in clinical Candida species isolated from Tunisian hospitals. Antimicrob Agents Chemother.2013; 57(7):3182- 93: https://aac.asm.org/content/57/7/3182.

Eddouzi J, Hofstetter V, Groenewald M, Manai M, Sanglard D. Characterization of a new clinical yeast species, Candida tunisiensis sp. nov., isolated from a strain collection from Tunisian hospitals.J Clin Microbiol.2013; 51(1):31-9: https://jcm.asm.org/content/51/1/31.

Eddouzi J, Chaieb K, Souiden Y, Bakhrouf A, Mahdouani K. Biofilm formation and virulence properties of Candida spp. isolated from hospitalised patients in Tunisia. Annals of Microbiology.2010; 60(3):481-488: https://doi.org/10.1007/s13213-010-0066-8.

RREFERENCES

Pr. A. ESKALEN, 1 Shields Ave. Davis, CA, 95616, Department of Plant Pathology University of California Davis: ad46il@r.postjobfree.com

Pr. D. SANGLARD, Institut de Microbiologie, CHUV, rue du Bugnon 48, 1011 Lausanne, Switzerland : ad46il@r.postjobfree.com

Pr. M.R. HAJLAOUI, Institut National de la Recherche Agronomique de Tunisie (INRAT), Rue Hedi Karray, 1004 ElMenzah, Tunis, Tunisia : ad46il@r.postjobfree.com

Pr. A. COSTE, Institut de Microbiologie, CHUV, rue du Bugnon 48, 1011 Lausanne, Switzerland : ad46il@r.postjobfree.com

Pr. Hong Jin Kim, Laboratory of Virology, College of Pharmacy, Chung Ang University, Seoul, South Korea: ad46il@r.postjobfree.com RESEARCH TOPICS

Doctoral studies

1- Identification and antifungal susceptibility of a large collection of yeast strains isolated in Tunisian hospitals In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used as a rapid method to identify yeasts isolated from patients in Tunisian hospitals. When identification could not be exstablished with this procedure, sequencing of the internal transcribed spacer with 5.8S ribosomal DNA (rDNA)

(ITS1-5.8S-ITS2) and D1/D2 domain of large-subunit (LSU rDNA) were employed as a molecular approach for species differentiation. Candida albicans was the dominant species (43.37% of all cases), followed by C. glabrata

(16.55%), C. parapsilosis (13.23%), C. tropicalis (11.34%), C. dubliniensis (4.96%), and other species more rarely encountered in human diseases such as C. krusei, C. metapsilosis, C. lusitaniae The in vitro antifungal activities of fluconazole and voriconazole were determined by the agar disk diffusion test and Etest, while the susceptibility to additional antifungal agents was determined with the Sensititre YeastOne system. Our results showed low incidence of azole resistance in C. albicans (0.54%), C. tropicalis (2.08%) and C. glabrata (4.28%). In addition, caspofungin was active against most isolates of the collection with the exception of two K. ohmeri isolates. This is the first report to describe caspofungin resistant isolates of this yeast. 2- Characterization of a new clinical yeast species, Candida tunisiensis sp. nov. The yeast strain JEY63 (CBS 12513), isolated from a 50-year-old male that suffered from oral thrush, could not be identified to the species level using conventional methods used in clinical laboratories. These methods include

(MALDI-TOF MS), germ tube formation, and the use of CHROMagar Candida and metabolic galleries. Sequence analysis of the nuclear rRNA (18S rRNA, 5.8S rRNA, and 26S rRNA) and internal transcribed spacer regions (ITS1 and ITS2) indicated that the ribosomal DNA sequences of this species were not yet reported. Multiple gene phylogenic analyses suggested that this isolate clustered at the base of the Dipodascaceae (Saccharomycetales, Saccharomycetes, and Ascomycota). JEY63 was named Candida tunisiensis sp. nov. according to several phenotypic criteria and its geographical origin. C. tunisiensis exhibited most probably a haploid genome with an estimated size of 10 Mb on at least three chromosomes. Using European Committee for Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) Candida albicans susceptibility breakpoints as a reference, C. tunisiensis was resistant to fluconazole (MIC = 8 μg/ml), voriconazole (MIC = 0.5 μg/ml), itraconazole (MIC = 16 μg/ml), and amphotericin B (MIC = 4 μg/ml) but still susceptible to posaconazole (MIC = 0.008 μg/ml) and caspofungin (MIC = Page 4 of 5

0.5 μg/ml). In conclusion, MALDI-TOF MS permitted the early selection of an unusual isolate, which was still unreported in molecular databases but could not be unambiguously classified based on phylogenetic approaches. 3- Molecular mechanisms of antifungal drug resistance in yeast pathogens The goal of my research was to investigate the mechanisms of resistance to antifungal agents at the molecular level in clinical yeast isolates acquiring drug resistance. Antifungal resistance of Candida species is a clinical problem in the management of diseases caused by these pathogens. In this study we identified from a collection of 423 clinical samples taken from Tunisian hospitals two clinical Candida species (Candida albicans JEY355 and Candida tropicalis JEY162) with decreased susceptibility to azoles and polyenes. For JEY355, the fluconazole (FLC) MIC was 8 μg/ml. Azole resistance in C. albicans JEY355 was mainly caused by overexpression of a multidrug efflux pump of the major facilitator superfamily, Mdr1. The regulator of Mdr1, MRR1, contained a yet-unknown gain-of-function mutation (V877F) causing MDR1 overexpression. The C. tropicalis JEY162 isolate demonstrated cross-resistance between FLC (MIC > 128 μg/ml), voriconazole (MIC > 16 μg/ml), and amphotericin B (MIC > 32 μg/ml). Sterol analysis using gas chromatography-mass spectrometry revealed that ergosterol was undetectable in JEY162 and that it accumulated 14α-methyl fecosterol, thus indicating a perturbation in the function of at least two main ergosterol biosynthesis proteins (Erg11 and Erg3). Sequence analyses of C. tropicalis ERG11 (CtERG11) and CtERG3 from JEY162 revealed a deletion of 132 nucleotides and a single amino acid substitution (S258F), respectively. These two alleles were demonstrated to be nonfunctional and thus are consistent with previous studies showing that ERG11 mutants can only survive in combination with other ERG3 mutations. CtERG3 and CtERG11 wild- type alleles were replaced by the defective genes in a wild-type C. tropicalis strain, resulting in a drug resistance phenotype identical to that of JEY162. This genetic evidence demonstrated that CtERG3 and CtERG11 mutations participated in drug resistance. During reconstitution of the drug resistance in C. tropicalis, a strain was obtained harboring only defective Cterg11 allele and containing as a major sterol the toxic metabolite 14α-methyl-ergosta-8,24(28)-dien-3α,6β-diol, suggesting that ERG3 was still functional. This strain therefore challenged the current belief that ERG11 mutations cannot be viable unless accompanied by compensatory mutations. In conclusion, this study, in addition to identifying a novel MRR1 mutation in C. albicans, constitutes the first report on a clinical C. tropicalis with defective activity of sterol 14α- demethylase and sterol Δ(5,6)-desaturase leading to azole-polyene cross-resistance. Postdoctoral studies

1- Human papillomavirus (HPV) and cervical cancer

There has been limited number of serology markers and no standardized method or criteria for the serologic assay in HPV research field. Therefore, the study for searching new serologic biomarkers and establishing strategy for diagnosis based on serology assay for detecting cervical cancer are high priority. The main objective of this project is to search new serologic markers and develop serologic strategy using serum anti-HPV E6, E7 and L1 antibodies as markers for detecting cervical cancer in tissue and serum of cervical cancer. Expression and purification of viral proteins (Glutathione S transferase fused E6 proteins and 6 histidine tagged E7 proteins were expressed in Escherichia coli, for L1 proteins were expressed in Saccharomyces cerevisiae and then purified by specific chromatography for each antigens) for three serotypes (HPV16/18 and 58). Using Enzyme linked immunoSorbent assays (ELISAs), the prevalence of nine serum antibodies (anti E6, E7 and L1 antibodies of HPV types 16, 18, and 58) were evaluated in normal (control) women and women with cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and cervical cancer.

The results showed that the frequencies of all types of anti HPV antibodies were higher in the CIN stages and cervical cancer than in normal women, and those of anti HPV16 E6 and E7, anti HPV18 E6 and E7, and anti HPV58 E7 antibodies were higher in the cervical cancer group than in the CIN stages. The frequencies of antibodies against HPV16, 18, and 58 E7 tended to increase with increasing severity of cervical lesions. However, there were few differences in the frequencies of antibodies against the L1 antigens of HPV16, 18 and 58 in cervical cancer versus CIN stages. 2- Human endogenous retroviruses, type K (group HERV-K(HML-2)) and breast cancer A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K transcription may be increased in human breast tumors. We hypothesized that HERV-K (HML-2) reactivation can serve as a biomarker for early detection of breast cancer. In this study, we used the same strategy as described for HPV and cervical cancer but only one antigen was evaluated. Expression and purification of the env gene of HERV-K HML-2 subtype was used to product Env protein after expression in E. coli (Glutathione S transferase fused env HERV-K HML-2) and purified by GST-affinity chromatography. 3- Oxidative stress and human health

Experimental and clinical studies indicate that oxidative stress plays a critical role in the initiation and progression of many diseases. In this project, we check the relationship between genetic polymorphisms in genes encoding antioxidant enzymes and the risk of development of several different types of diseases (including: Cancer, diabetes, cardiovascular and neurological diseases) in Tunisia population.

4- Molecular tools for detection of plant pathogenic fungi Plant pathogenic fungi are the causal agents of the most detrimental diseases in plants, including economically important crops, provoking considerable yield losses worldwide. Detection and accurate identification of plant pathogens is one of the most important strategies for controlling plant diseases to initiate preventive or curative measures. In this study, the identification of fungi was based on the morphology of reproductive structures and phylogenetic analyses of the gene Page 5 of 5

regions ITS, translation elongation factor1 alpha (Tef1-α), Beta-tubulin and glyceraldehyde-3-phosphate dehydrogenase

(GPDH).

Enzymax 36-Laboratoires has developed different complex enzyme to fight phytopathogenic fungi. Under the supervision of Dr. MR Hajalaoui (Laboratoire Biotechnologie Appliquée à l'Agriculture, Institut National de la Recherche Agronomique de Tunisie), we have evaluated two enzymatic complexes: (i) for the control of postharvest fungal disease of citrus fruits. (ii) For the management of Grapevine trunk diseases. (Confidential data for the benefit of Enzymax 36-Laboratoires).

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