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Denis


LIFE SCIENTIST || EPIGENETICIST || DATA ANALYST || COMPUTATIONAL BIOLOGIST

I am a research engineer focusing on applications of systems biology approaches in immune-epigenomics. During my education, I gathered broad knowledge in genetics, cancer biology, environmental effects on cancer etiology, epigenetics, immunology, and computational systems biology. I have leveraged cutting-edge technologies and innovative computational approaches to study human physiology and disease in all my projects. The algorithms that I developed have revealed novel concepts in cancer and immunology. My multidisciplinary background, diverse skills, and proactive personality have afforded me collaborative projects published in Science and corresponding authorships in high-impact journals, highlighting early scientific independence in my career.

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Denis


LIFE SCIENTIST || EPIGENETICIST || DATA ANALYST || COMPUTATIONAL BIOLOGIST

I am a research engineer focusing on applications of systems biology approaches in immune-epigenomics. During my education, I gathered broad knowledge in genetics, cancer biology, environmental effects on cancer etiology, epigenetics, immunology, and computational systems biology. I have leveraged cutting-edge technologies and innovative computational approaches to study human physiology and disease in all my projects. The algorithms that I developed have revealed novel concepts in cancer and immunology. My multidisciplinary background, diverse skills, and proactive personality have afforded me collaborative projects published in Science and corresponding authorships in high-impact journals, highlighting early scientific independence in my career.

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Education


2014

Ph.D. in Genetics
Department of Biosciences
University of Helsinki - Finland

Thesis: Biochemical effects of inherited MMR gene mutations and diet on colorectal cancer risk 

2009

M.Sc. with honors in Biotechnology
Faculty of Food Technology and Biotechnology, 
University of Zagreb, Croatia 

Education


2014

Ph.D. in Genetics
Department of Biosciences
University of Helsinki - Finland

Thesis: Biochemical effects of inherited MMR gene mutations and diet on colorectal cancer risk 

2009

M.Sc. with honors in Biotechnology
Faculty of Food Technology and Biotechnology, 
University of Zagreb, Croatia 

PhD Education

Awards & Grants

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Projects | Scientific interests


Projects | Scientific interests


ACTIVE:

SINGLE CELL TECHNOLOGIES AND DEVELOPMENT OF ANALYSIS METHODS

High-dimensional immunophenotyping (FACS/CyTOF/single cell RNA-seq) of developing and renewing cell populations holds the potential to elucidate developmental sequences or ‘trajectories’. Differentiated cells develop from stem and progenitor cells through a sequential series of phenotypic and gene expression changes. Recent advances in the trajectory analysis show promise in ordering cells along predefined developmental pathways, but existing algorithms lack the ability to elucidate complex branching developmental paths or relationships in an unsupervised manner. To address this, I have developed the concept of ‘trajectory space’, in which each cell in a population is described not by its expression of phenotypic markers, but by its shortest ‘trajectory’ distance to every other cell, within k-nearest neighbor graph. Visualization of cell relationships in high-dimensional trajectory space is achieved through standard dimensionality reduction approaches (e.g. PCA, tSNE) to reveal complex developmental sequences. More


Thymic Trafficking of Mucosal Dendritic Cells in Oral Tolerance

We seek to understand the thymic mechanisms in oral tolerance. Insights from the ongoing studies may lead to rational approaches for more effective clinical oral tolerance protocols such as targeting younger individuals with a higher thymic T cell output or designing Ag peptides that elicit the development of immunosuppressive thymic T cell populations versus clonal deletion of Ag-specific thymocytes.


Effect of interplay between DNA mismatch repair proteins and chromatin on local mutation frequency

One of the most common inherited colorectal cancers (CRC), Lynch syndrome (LS), accounts for 2-4% of all CRC cases. The susceptibility is caused by germline mutations in the genes MLH1, MSH2, MSH6, MSH3 and PMS2, which encode proteins responsible for DNA mismatch repair (MMR). MutS⍺ (MSH2/MSH6 heterodimer) or MutSβ (MSH2/MSH3 heterodimer) recognize, bind to, and initiate the repair of base-base mismatches and small insertions/deletions. MutSβ recruits MutL⍺ (MLH1/PMS2 heterodimer), which recruits proteins responsible for the downstream repair processes. Moreover, it has been shown that MSH6, but not MSH3, has a strong binding affinity to histone 3 lysine 36 trimethylation (H3K36me3), through a PWWP (Pro-Trp-Trp-Pro) domain and postulated that the H3K36me3 directs human MMR in vivo by recruiting MutS onto chromatin. However, it is unknown, (i) how H3K36me3 landscape affects the local mutation frequency in normal cells and (ii) how mutations in the PWWP domain of MSH6 found in putative LS families affect the MutS binding affinity to H3K36me3.

We study the interplay between MMR, H3K36me3 and repair efficiency, in the context of normal and defective MMR. The main hypothesis is that local abundance of H3K36me3 in chromatin affects the recruitment of MutS⍺, which is reflected in de novo mutations rates. We are examining effects of H3K36me3 in a study using T cells of a wild type (WT) and Mlh1 -/- mice; the latter are MMR-deficient and develop T cell lymphomas by the age of 7 months.

Moreover, we are interested in the effect of mutations within the PWWP domain of MSH6, found in putative LS families, on its interaction with H3K36me3. This study holds potential to clarify novel layer of MMR regulation in vivo and have direct impact on clinical work since verification of pathogenic mutations allows correct counseling of Lynch syndrome patients.


  • PAST: GENETIC AND ENVIRONMENTAL FACTORS IN COLORECTAL CANCER TUMORIGENESIS

    Genetic and lifestyle factors have been shown to predispose to cancer. In particular aim is to understand how Western diet affects normal colon mucosa and creates environment that promotes tumorigenesis.  

  • PAST: FUNCTIONAL CHARACTERIZATION OF MUTATIONS IN MISMATCH REPAIR GENES ASSOCIATED WITH LYNCH SYNDROME

    Lynch syndrome (LS), inherited colorectal cancer, is linked to germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS2. In order to offer contiguous pre-symptomatic surveillance and predictive gene counseling to mutation carriers, we need to asses level of pathogenicity of a mutation. I am interested in applying novel assay to characterize MSH6 mutations that are associated with cancers but showing no defects in commonly used assays such as in vitro mismatch repair assay.

  • PAST: Sequencing and genotyping of Siberian Jay
  • PAST: Effect of mutagens and antimutagens on the molecular processes in the cell
     
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Blog news


Blog news


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Free time


“For most gulls it was not flying that matters, but eating. For this gull, though, it was not eating that mattered, but flight.” 
― Richard Bach, Jonathan Livingston Seagull

Experience of war in Croatia taught me to appreciate present moments, be focused but keep open eyes on future perspectives and that truly lasting in this world is knowledge and wisdom that we gain. 

Free time


“For most gulls it was not flying that matters, but eating. For this gull, though, it was not eating that mattered, but flight.” 
― Richard Bach, Jonathan Livingston Seagull

Experience of war in Croatia taught me to appreciate present moments, be focused but keep open eyes on future perspectives and that truly lasting in this world is knowledge and wisdom that we gain. 

Most of my activities and interests are in the gallery, but I do like great science fiction books (e.g., by Isaac Asimov, Roger Zelazny, Orson Scott, Arthur C. Clarke...), which tackle some other important aspects of society or human nature and behaviour. 

I am quite social person and moving from town to town during my life as well as changing countries made certain pressure to build up social circle fast, so I participate in CouchSurfing because it is great way to meet diverse people all over the world.