Vinod Kumar Magadi Gopalaiah, PhD
Vasiliki Matzaraki, PhD student: Genetic susceptibility to candidemia
Kieu Le, PhD student: Functional genomics approach to sepsis
Isis Ricaño-Ponce, PhD student: Genetics and genomics of celiac disease associated variants
Overview of my current research
My research team aims to identify human genes and molecular mechanisms that regulate appropriate immune response and may contribute to susceptibility to infectious and immune diseases.
I have always had a strong interest in deciphering the molecular mechanisms in disease, particularly in infectious diseases. I first focused on discovering susceptibility genes, but have also made the transition to gene function characterization by integrating different types of molecular data and by bridging the fields of bioinformatics, genetics, immunology and clinical sciences.
1. Systems genetics approach to immunity Research into infectious diseases has only recently started to look for causal factors using genetics. However, the traditional approaches have not been very successful. By taking advantage of state-of-the-art technologies and by simultaneously assessing genetics, transcriptomics and immune-profiling in the context of host-pathogen interaction, we are generating new hypotheses to open avenues for further investigation and targeted drug discovery. For this we have initiated an important collaboration with Prof. Mihai Netea (Radboud University, Nijmegen) to explore the impact of genetic variation on immune parameters in large population-based cohorts ( http://www.humanfunctionalgenomics.org/ ).
Li Y*, Oosting M*, Smeekens S*, Jaeger M*... Joosten LAB*, Wijmenga C*, Netea M*, Kumar V*. A functional genomics approach identifies a strong genetic component in human cytokine responses. Nature Medicine 2016; Epub ahead of print 4 July 2016. doi:10.1038/nm.4139
Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. mTOR-and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity. SCIENCE 2014;345(6204):1250684.
Saeed S, Quintin J, Rao AN, Kerstens H, … Kumar V, et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. SCIENCE 2014; 345(6204):1251086.
2. Candidemia as a model disease for infectious disease Candidemia is a systemic fungal infection in the bloodstream, mainly caused by Candida albicans; it leads to approximately 150,000 deaths worldwide every year. The only treatments are anti-fungal drugs, which are often ineffective. However, it is difficult to develop new treatment options with our limited knowledge of the host genetic susceptibility factors and their impact on host-Candida interactions, which are central to the development of candidemia. We hypothesize that comprehensive characterization of the genetic and molecular basis of the Candida-specific immune response will pinpoint key susceptibility factors. Identifying the susceptibility pathways will aid the development of new therapies for candidemia.
Currently we are testing our hypothesis by : (1) identifying the molecular and immune pathways induced by C.albicans in immune cells isolated from a population cohort , (2) discovering the impact of genetic variation on Candida-induced pathways and individual susceptibility to candidemia, and (3) constructing and validating a Candida-specific regulatory network. This information will not only offer insight into the molecular mechanism of Candida infection, but also provide leads for therapeutic targets.
We are also applying this new interdisciplinary approach to identify susceptibility genes for other complex fungal infectious diseases, such as Recurrent vulvovaginal candidiasis (RVVC) and Allergic Bronchopulmonary Aspergillosis (ABPA).
Kumar V *, Cheng S*, Johnson MD*… Wijmenga C, Netea MG. Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia . Nature Communications 2014;5:4675.
Kumar V * , Smeekens SP*, Ng A*, Johnson AD, Platinga TS, Diemen C, et al. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nature Communications 2013;4:1342.
3. Tuberculosis risk in type 2 diabetes Diabetes (DM) triples the risk of developing yuberculosis (TB). Consequently, the alarming growth of type 2 diabetes in TB-endemic countries and among people originating from these countries poses a serious threat to global TB control. There is a lack of evidence to support many of the recently advocated guidelines for the care and control of TB and DM, and a lack of understanding of the mechanisms underlying the effect of DM on TB susceptibility and treatment outcome. As part of a KP7 EU project called “TANDEM” ( http://www.tandem-fp7.eu/), we are unravelling the genetic susceptibility to concurrent tuberculosis and diabetes.
For the TANDEM Consortium Reinout van Crevel, Hazel M Dockrell. TANDEM: understanding diabetes and tuberculosis. The Lancet Diabetes and Endocrinology 2014
Selected recent publications
See full list of papers in Google Scholar, *equal contribution, IF impact factor according to Web of Science
- Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs
- I Ricaño-Ponce, DV Zhernakova, P Deelen, O Luo, X Li, A Isaacs, ... Journal of autoimmunity 2016;68:62-74
- GWAS as a Driver of Gene Discovery in Cardiometabolic Diseases. B Atanasovska, V Kumar, J Fu, C Wijmenga, MH Hofker. Trends in Endocrinology & Metabolism 2015;26 (12):722-732
- A systems genetics approach to Candida infection. V Matzaraki, I Ricano, I Jonkers, L Franke, Y Li, C Wijmenga, MG Netea, ... MYCOSES 2015;58:177-177
- Contrasting the genetic background of type 1 diabetes and celiac disease autoimmunity. J Gutierrez-Achury, J Romanos, SF Bakker, V Kumar, EC de Haas, ... Diabetes Care 2015;38 (Supplement 2):S37-S44
- The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections. M Jaeger, R van der Lee, SC Cheng, MD Johnson, V Kumar, A Ng, ... European Journal of Clinical Microbiology & Infectious Diseases 2015;34 (5):963-974
- Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism. V Kumar, C Wijmenga, RJ Xavier. Current Opinion in Immunology 2014;31:51-57
- Kumar V *, Cheng S*, Johnson MD*… Wijmenga C, Netea MG. Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidemia. Nature Communications 2014 Sept ;5:4675 (IF 10.74)
- Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. Epigenetic profiling identifies mTOR/HIF1α-dependent induction of glycolysis as the cellular metabolic basis of trained immunity. SCIENCE 2014 Sept;345(6204):1250684. (IF 31.03)
- Saeed S, Quintin J, Rao AN, Kerstens H, … Kumar V, et al. Epigenetic programming during monocyte to macrophage differentiation and trained immunity. SCIENCE 2014 Sept;345(6204):1251086. (IF 31.03)
- Kumar V , Westra HJ, Karjalainen J., et al. Human disease-associated genetic variation impacts large non-coding RNA expression. PloS Genet. 2013;9(1):e1003201. (IF 8.16) Free PMC aricle
- Kumar V* , Smeekens SP*, Ng A*, Johnson AD, Platinga TS, Diemen C, et al. Functional genomics identifies type 1 interferon pathway as central host defense against Candida albicans. Nature Communications 2013;4:1342. (IF 10.74)
- Romanos J, Rosén A, Kumar V, Trynka G, ... Wijmenga C; PreventCD Group. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants. Gut 2013 Jun 7. Free article
- Kumar V, Wijmenga C, Withoff S. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Semin Immunopathol . 2012 Jul;34(4):567-80. doi: 10.1007/s00281-012-0312-1. Free review
During my MSc work (Bangalore, India), I was the first person to isolate and characterize a bacteriophage which is currently being used as an effective therapeutic tool to control Vibrio harveyi infection in shrimp (Aquaculture, 2006). During my PhD I showed that polymorphisms within innate immunity genes significantly modulate disease severity by influencing Pseudomonas aeruginosa infection among cystic fibrosis patients (Human Genetics, 2006; Genes and Immunity, 2008; Am J Med Gen, 2011), which could be potential biomarkers to identify cystic fibrosis patients with greater risk.
In my first postdoctoral project (2008-2011), I identified genetic susceptibility variants for hepatitis C virus induced hepatocellular carcinoma (Nature Genetics, 2011), hepatitis B virus infection (Human Molecular Genetics, 2011) by GWAS. I also showed that the results of genetic association studies can be translated into clinical application by demonstrating that soluble MICA quantification has a potential as a biomarker for HBV-induced liver cancer patients survival (Plos One 2012).
I obtaining a University Merit Scholarship for my Master’s course and was therefore able to specialize in microbiology (2001–2003) at GKVK University of Agricultural Sciences, Bangalore, India. I was later awarded a German Research Council (DFG) PhD fellowship (2003–2007) to participate in an international research programme at the University of Hannover.
After completing my PhD in infection genetics, I obtained a 3-year postdoctoral position (2008–2011) at the University of Tokyo, one of the top 10 universities in the world. In 2011, I moved to UMCG, Groningen, the Netherlands to take up a postdoc position with Prof. Cisca Wijmenga and was appointed assistant professor in 2016.
|Laatst gewijzigd:||05 juli 2016 11:32|