Sirinart Aromseree

Name: Sirinart Aromseree, Ph.D.

POSITION TITLE: Lecturer, Department of Microbiology, Faculty of Medicine, Khon Kaen University

EDUCATION/TRAINING

A. Positions and Honors

Positions

2017-current Lecturer, Department of Microbiology, Faculty of Medicine, Khon Kaen University, Thailand

2016-2017 Postdoctoral researcher in DENGUE-INDEX project funded by Research Council of Norway

B. Significant contributions to science:

1. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) associated with squamous cell carcinoma

High risk HPVs are recognized as cause of cervical cancer and associated with several malignancies such as oral squamous cell carcinoma (OSCC). EBV, also a well-known DNA tumor virus, has been linked to development of several kinds of malignancies. Under intensive investigation of our research group named “HPV, EBV and carcinogenesis (HEC)”, cervical cancer in northeastern populations have been studied providing common HPV genotypes in this population, innate immune modulation by HPV E2 protein and suggesting about the episomal status of HPV is involved in cervical cancer development. Our novel finding supported the hypothesis that differential methylation of the E2BSs 1, 3 and 4 is related to the activation of viral oncogene expression in cervical lesions as long as the viral genome remains in the episomal state. Once the virus becomes integrated into host cell chromosomes these methylation patterns may be substantially altered due to complex epigenetic changes of integrated HPV genomes. However, episomal status of HPV is still needed to be elucidated for the potential role in HPV carcinogenesis. We also introduced the specific risk factors and potential role of HPV and EBV in OSCC. However, the molecular pathogenesis is needed to be further investigated. In addition, co-infection of EBV is commonly found in HPV-associated cancer corresponding with our study. Until now, roles of HPV and EBV co-infection or co-detection in squamous cell carcinoma (SCC) is controversial. Therefore, we are interested to investigate of the possible contributing role of EBV in tumorigenesis of HPV-associated cancers such as cervical cancer and head and neck squamous cell carcinomas (HNSCCs) especially oral and nasal cancers. To achieve our objectives, we havecollectedvarious types of specimens including blood,fresh-frozen tissues, formalin-fixed paraffin embedded (FFPE) tissues, etc. of different lesions of cervix, and also from oral and nasal cancer patients. Using thesesamples providing by clinicians in our research group, we have been investigating the interaction of HPV and EBV and virus-host interaction using proteomic analysis, RNA sequencing, cancer cell line establishment and tumorigenesis studying in vitro. The findings give rise to the new insights of HPV, EBV and other DNA tumor viruses as well as co-infection-associated carcinogenesis. We aim to apply the knowledge in the aspect of cancer prevention, diagnosis and therapy.

2. Roles ofextracellular microvesicles in viral associatedcancers and other viraldiseases.

As emerging of extracellular vesicles (EVs) roles in several types of cancers, they are attracting interest in the scientific community due to their role in intercellular communication and have been recognized as powerful mediators of extracellular communication. We succeeded in determining the mechanism of EBV-modified exosomes in the induction of proinflammatory cytokines in monocyte-derived dendritic cells (MoDCs) that may influence on the imbalance of a proinflammatory cytokine production in tumor microenvironment. This result mightdescribe some roles of EBV coinfection with HPV-associated cervical cancer. We are going to investigate the mechanism of EVs in viral-associated cancer development and in other viral diseases that are focused on some mosquito-borne viruses such as dengue virus and chikungunya virus.

3. New emerging viruses in mosquitoes

Emerging and re-emerging viruses are important event in new disease emergence. Genetic changes in the pathogen is the most important event that make the virus possible to become established in a new host species, productively infect new individuals in the new hosts (typically humans) and create local, regional or worldwide health threats. One of our interest is about emerging and re-emerging arboviruses. Despite various vector control measures, there continues to be emergence and resurgence of such diseases. We collected mosquitoes from the houses of selected communities in northeast of Thailand and some provinces in Laos. We aim to find some emerging or re-emerging viruses in mosquitoes using metagenomic analysis. The information can be used to apply in planning for the diagnosis method development, prevention of the disease outbreak.

C. Research ongoing and support

1. Determination of entomological indices to assess dengue transmission, predict dengue outbreaks, and evaluate vector control interventions (DENGUE-INDEX)

Funding:Research Council of Norway (2016-2019)

Roleinthisproject: co-investigator

2. Extracellular Microvesicles and their role(s) in pathogenesis of dengue virus.

Funding:Research Council of Norway (2016-2019)

Role in this project: Primary investigator

3. Effects of climate change and variability on community vulnerability and exposure to dengue in South East Asia (DENCLIM)

Funding:Norwegian University of Life Sciences, Norway (2018-2021)

Role in this project:co-investigator

4. The roles of tumor viruses in epigenetic alteration, immune evasion on carcinogenesis and new immune stimulation strategy for cancer therapy

Funding:Khon Kaen University, Khon Kaen, Thailand (2017-2018)

Role in this project:co-investigator

5. Development of screening test for oral squamous cell carcinoma from saliva using lateral flow immunochromatography

Funding:National Science Technology and Innovation Policy Office, Thailand(2017-2018)

Role in this project:co-investigator

D. Supervision

Under the supervision of

Prof. Chamsai Pientong,M.D., Ph.D.

Head of HEC research group

Principal investigator (Thai) of DENGUE-INDEX and DENCLIM

Assoc. Prof. Tipaya Ekalaksananan, M.D.

Deputy head of HEC research group

E. Publication

1. Sirinart Aromseree, Jaap M. Middeldorp, Chamsai Pientong, Monique van Eijndhoven, Octavia Ramayanti, Sinead M. Lougheed, D. Michiel Pegtel, Renske D. M. Steenbergen, Tipaya Ekalaksananan. 2017. High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7. PLoS ONE, 12 (1): e0169290. http://doi:10.1371/journal.pone.0169290.

2. Sirinart Aromseree, Chamsai Pientong, Piyawut Swangphon, Arkom Chaiwongkot, Natcha Patarapadungkit, Pilaiwan Kleebkaow, Thumwadee Tungsiriwattana, Bunkerd Kongyingyoes, Tineke Vendrig, Jaap M. Middeldorp and Tipaya Ekalaksananan. 2015. Possible contributing role of Epstein-Barr virus (EBV) as a cofactor in human papillomavirus (HPV)-associated cervical carcinogenesis. Journal of Clinical Virology, Volume 73, Pages 70-76. http://dx.doi.org/10.1016/j.jcv.2015.10.015.

3. Sirinart Aromseree, Arkom Chaiwongkot, Tipaya Ekalaksananan, Bunkerd Kongyingyoes, Natcha Patarapadungkit, and Chamsai Pientong. 2014. The Three Most Common Human Papillomavirus Oncogenic Types and Their Integration State in Thai Women with Cervical Precancerous Lesions and Carcinomas. Journal of Medical Virology, Volume 86, Issue 11, Pages 1911-1919. http://dx.doi.org/10.1002/jmv.24034.