Çocuk Karaciğer Hastalıkları Araştırma Laboratuvarı-KUTTAM
https://kuttam.ku.edu.tr/
Scope and future perspectives of the group:
Our group aims at the investigation and treatment of paediatric liver diseases and the post liver transplantation immune monitoring of the patients. Specifically, we will utilize flow cytometry, FACS and next generation sequencing (NGS) method to discover respectively the immunopathology and underlying mutations in general and cholestasis related genes. These studies will identify mechanisms of disease and will guide the development of new diagnostics and therapeutics. To that end, our group has applied to several funding bodies to initiate and sustain several projects, applied to Koç university ethical committee and has initiated postgraduate immunology courses for Phd students and candidates.
As of 2020, the Immunology Phd/Msc programs have initiated at Koç University. Even more, this program provides detailed Transplantation immunology courses and will encompass a top-notch immunology lab required for tissue typing and panel reactive antigen detection by multi-colour flow cytometry. This set-up will also enable us to expedite translational research.
As most of our team-members have international connections, we envisage to increase our participation with international networks. (https://kuttam.ku.edu.tr).
Ongoing projects:
- Identify biomarkers and genetic traits associated with cholestatic and autoimmune liver diseases allowing improved risk stratification and personalized therapies.
- Immuno-genetic investigation in pre and post liver transplant paediatric patients
- Bregs in the monitoring of liver graft in paediatric liver transplantation
- Immunologic investigation of non-responders in autoimmune hepatitis
- Immunologic investigation of DILI in paediatrics
- Investigation of the pathogenesis of eosinophilic oesophagitis (EoE)
- Investigation of IgE and non IgE mediated allergies post liver transplant in children
- Investigation of Immune and genetic mechanisms in EBV mediated post-transplant immune mediated disorders
DOKTORA ÖĞRENCİLERİ
Dr Muhammed Yüksel
Dr Muhammed Yüksel has acquired his Bachelor, Master and PhD degrees at Ghent University Hospital in Belgium. His PhD in immunology was about the “Validation of a mouse model of autoimmune hepatitis (AIH)” and after the first 1,5 years at Ghent University, he went to Yale University (USA) for over 2 years and established two mouse models of AIH in NOD mouse expressing HLA-DR3 or HLA-DR4. Following his extensive immunologic training at Yale he went on to apply this knowledge at The Institute of Liver Studies at King’s College London (UK), elucidating human AIH. Consequently, Dr Yuksel is investigating the pathophysiology of AIH in children, adults and pregnant women since 2010 gaining awards from European/American institutions such as EASL, AASLD, VVGE and ESGHAN. Notably, the complex interplay between class-II HLA’s (DR3, DR7 and DR13 among others) and regulatory T cells (Tregs) dysfunction and mechanisms of treatment failure in AIH is his main interest. There is compelling evidence that new agents such as interleukin-2 and short chain fatty acids can correct Tregs dysfunction. Even more, the elucidation of genetic variations in AIH through an unbiased method such as next generation sequencing (NGS) is paramount to (i) understand and on long-term to (ii) control and eventually cure AIH
Selected Publications
Yuksel M, Akturk H, Arikan C. Immune monitoring of a child with autoimmune hepatitis and type 1 diabetes during COVID-19 infection. Eur J Gastroenterol Hepatol 2020 Sep;32(9):1251-1255
Jassem W, Xystrakis E*, Ghnewa YG*, Yuksel M, Pop O, Martinez-Llordella M, Jabri Y, Huang X, Lozano JJ, Quaglia A, Sanchez-Fueyo A, Coussios CC, Rela M, Friend P, Heaton N, Ma Y. Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the
liver and promotes regeneration. Hepatology. 2018 Dec 18. doi: 10.1002/hep.30475. (IF=14) * Shared first authorship.
Yuksel M*, Xiao X*, Tai N, Manakkat Vijay G, Gülden E, Beland K, Lapierre P, Alvarez F, Hu Z, Colle I, Ma Y and Wen L. The induction of autoimmune hepatitis in HLA-DR4 NOD mice. Clinical Experimental Immunology 2016 July doi: 10.1111/cei.1284 (IF=3.148) * Shared first authorship
Yuksel M*, Wang Y*, Tai N, Peng J, Guo J, Beland K, Lapierre P, David C, Alvarez F, Colle I, Yan H, Mieli-Vergani G, Vergani D, Ma Y and Wen L. A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation. Hepatology 2015 July;62(5):1536-50. (IF:11.055) * Shared first authorship
Xystrakis E*, Yuksel M*, Lin F, Huang X, Tiberiu PO, Quaglia A, Heaton N, Prachalias A, Rela M, Fuggle S, Ma Y and Jassem W. Impact of donation mode on the proportion and function of T lymphocytes in the liver. PLOS One 2015 Oct 29;10(10):e0139791. doi: 10.1371 (IF:3.234) * Shared first authorship
Liberal R, Grant C, Yuksel M, Graham J, Kalbasi A, Ma Y, Heneghan M, Diego Vergani, Vergani GM, Vergani D, Longhi MS. Treg conditioning endows activated Teff with suppressor function in autoimmune hepatitis/autoimmune sclerosing cholangitis. Hepatology 2017 (IF:11.71)
Halim L, Romano M, McGregor R, Correa I, Pavlidis P, Grageda N, Hoong SJ, Yuksel M, Jassem W, Hannen RF, Ong M, Mckinney O, Hayee B, Karagiannis SN, Powell N, Lechler RI, Nova-Lamperti E, Lombardi G. An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment. Cell Rep.2017 Jul 18;20(3):757-770.
Dr Farinaz Nazmi
I acquired my Bachelor in cellular and molecular biology- Biochemistry and Molecular Genetic master’s degrees at Tabriz University, Iran. My Master thesis was “Evaluating combination effects of All-trans retinoic acid (ATRA) & nucleostemin gene knock down in human acute promyelocytic leukemia NB4 cells”. At the same time, I presented a predicted 3D structure of the nucleostemin protein using structure prediction software. After graduation, I became a research assistant in the Colorectal Cancer Department of Iran University Hospital, working on the use of long noncoding RNAs as diagnosis biomarkers in colorectal cancer. I started on the next stage of my career working in a medical genetic laboratory, being extensively trained in the field of chromosome karyotyping and analysis.
Currently, I am PhD student at Koç University Graduate School of Health Sciences Immunology program. I am working in the field of monitoring pediatric liver transplantation in the Prof. Dr. Çiğdem Arıkan laboratory.
Ms. Zeynep Ece Kuloğlu
Zeynep Ece Kuloğlu, Date of Birth:13/01/1999. She Graduated from İstanbul Technical University- Molecular Biology and Genetics Department with Bachelor’s degree in 2020. She has been a Project Manager of a financially supported Tübitak 2209-A Project. As of 2020 She is a Master student in Arıkan Lab.
Publications
Previous publications: ‘Investigation of the effects of HDACi on the eosinophil maturation and inflammasome activation’ (Turkish Journal of Immunology) 2020.