Vinod Kumar Magadi Gopalaiah, PhD

PhD thesis, 2007. European CF Twin and Sibling Study; Genetic Susceptibility to Infectious Diseases. Hannover University, Germany

Email, Full list of papers in Google Scholar

News

• 2018: Appointed Assistant Professor and Hypatia Fellow, Radboud Institute for Health Sciences, Infectious Diseases and Global Health, Radboud University Medical Center, Nijmegen
• 2018: Awarded a Hypatia Fellowship (€1 million). Radbound UMC, Nijmegen. "Systems Genetics Approach to Infectious Diseases"
• 2015: Appointed Assistant Professor, Department of Genetics, University Medical Center Groningen

Research

Vinod Kumar leads the immune-genetics and infectious disease research group in identifying the human genes and molecular mechanisms that regulate appropriate immune response to infections, and which may contribute to susceptibility to sepsis and other infectious diseases.

Infections have an enormous impact on human health. My team is interested in deciphering the genetic and molecular mechanisms in disease, particularly infectious diseases. By taking advantage of state-of-the-art technologies and simultaneously assessing genetics and multi-omics in the context of host-pathogen interaction (http://www.humanfunctionalgenomics.org/), we are discovering druggable pathways to treat infectious diseases and developing genetic and genomic biomarkers for precision medicine.

Sepsis, a heterogeneous disorder caused by infections

Sepsis is a major global health problem primarily caused by bacterial and fungal infections. It is a life-threatening disorder characterized by a dysregulated immune response and multi-organ dysfunction. Current strategies using a “one-size-fits-all” treatment approach for sepsis have failed because of the extreme heterogeneity in disease outcome. Factors such as host genetics, pathogens and environmental factors, as well as the unique interaction between these factors in every individual, may contribute to heterogeneity in sepsis. Understanding the impact of these complex interactions on the function of the relevant cell types is therefore crucial to delineating the molecular basis of heterogeneity in outcome.

To do this, we are currently performing systems genetic studies using both patient and population-based cohorts. In particular, we are investigating how genetically determined inter-individual differences in molecular responses to infections contribute to the heterogeneity of fungal and bacterial sepsis outcome. Dissecting the genetic basis of sepsis heterogeneity to infections is a major step towards novel patient-specific therapeutic strategies, which depend on a deep understanding of the molecular interactions between host and pathogens.

Research group members

Current

• 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

Former

• Rodrigo Almeida, PhD 2014, "Beyond genome wide association studies in celiac disease by exploring the non-coding genome"
• Barbara Hrdlickova, PhD 2014, "Finding the missing 'LiNCs' in celiac disease"
• Luz Maria Medrano de Dios, Postdoc, now at University of Valenica, Spain

Selected publications

See full list of papers in Google Scholar, *equal contribution

• Functional Annotation of Genetic Loci Associated With Sepsis Prioritizes Immune and Endothelial Cell Pathways. Le KTT, Matzaraki V, Netea MG, Wijmenga C, Moser J, Kumar V. Front Immunol. 2019 Aug 14;10:1949. doi: 10.3389/fimmu.2019.01949. eCollection 2019.
• A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans. Jaeger M, Matzaraki V, Aguirre-Gamboa R, Gresnigt MS, Chu X, Johnson MD, Oosting M, Smeekens SP, Withoff S, Jonkers I, Perfect JR, van de Veerdonk FL, Kullberg BJ, Joosten LAB, Li Y, Wijmenga C, Netea MG, Kumar V. J Infect Dis. 2019 Jul 31;220(5):862-872. doi: 10.1093/infdis/jiz206.
• An integrative genomics approach identifies novel pathways that influence candidaemia susceptibility V Matzaraki, MS Gresnigt, M Jaeger, I Ricaño-Ponce, MD Johnson, ...V Kumar. PloS one 2017;12(7)
• Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi Y Li, M Oosting, P Deelen, I Ricaño-Ponce, S Smeekens, M Jaeger, ... C Wijmenga*, LA Joosten*, MG Netea*, V Kumar*. Nature Medicine 2016;22, 952–960.
• A functional genomics approach to understand variation in cytokine production in humans Y Li, M Oosting, SP Smeekens, M Jaeger, R Aguirre-Gamboa, KTT Le, ... MG Netea*, V Kumar*. Cell 2016;167(4), 1099-1110. e14
• 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
• Systematic annotation of celiac disease loci refines pathological pathways and suggests a genetic explanation for increased interferon-gamma levels V Kumar, J Gutierrez-Achury, K Kanduri, R Almeida, B Hrdlickova, ... Human Molecular Genetics 2015;24(2), 397-409
• 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
• Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia V Kumar*, S Cheng*, MD Johnson*, … C Wijmenga, MG Netea. Nature Communications 2014;5:4675
• Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity B Hrdlickova, V Kumar, K Kanduri, DV Zhernakova, S Tripathi, ...
  Genome Medicine 2014;6(10), 88
• mTOR-and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity SC Cheng, J Quintin, RA Cramer, KM Shepardson, S Saeed, V Kumar, ... Science 2014;345(6204):1250684.
• Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity S Saeed, J Quintin, HHD Kerstens, …V Kumar, ... Science 2014;345(6204):1251086.
• Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants J Romanos, A Rosén, V Kumar, G Trynka, L Franke, A Szperl, ... Gut 2014;63(3), 415-422. Free article
• Human disease-associated genetic variation impacts large intergenic non-coding RNA expression V Kumar , HJ Westra, J Karjalainen, ... PloS Genet. 2013;9(1):e1003201.
• Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans V Kumar* , SP Smeekens*, A Ng*, Johnson AD, ... Nature Communications 2013;4:1342.
• From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. V Kumar, C Wijmenga, S Withoff. Semin Immunopathol . 2012;34(4), 567-80. Free review
• Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma V Kumar, N Kato, Y Urabe, A Takahashi, R Muroyama, N Hosono, ... Nature Genetics 2011;43(5), 455

Research achievements

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).

Academic background

I obtained 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.