Jacob Giehm Mikkelsen

Group Leader

Jacob Giehm Mikkelsen
Associate Professor, PhD
More information 

 

RESEARCH
Efficient insertion of transgenes into chromosomal DNA is a fundamental aim in both therapeutic gene transfer and genetic engineering for animal transgenesis. We study the biology and therapeutic properties of mobile nucleic acids. Our main focus is the insertion of foreign DNA into chromosomal DNA of mammalian cells and animals. We explore viral and nonviral gene delivery technologies in relation to transgenesis, genetic therapy, and translational medicine.

We are devoted to basic studies of vector methodology and biology as well as to studies of therapeutic vector applicability in relevant animal models. Major emphasis is given to integrating vector technologies including DNA transposon-based vector systems – such as Sleeping Beauty – as a tool for nonviral gene insertion and retro- and lentiviral vector systems for efficient in vivo gene transfer and ex vivo applications. Recent efforts in the lab have included the development of tools for animal transgenesis with particular emphasis on engineering of transgenic cloned pigs as animal models for human disease. This work aims primarily at developing large animal models of inflammatory disease.

A substantial part of our work explores non-coding RNAs (shRNAs and miRNAs) and the use of vector-encoded miRNA inhibitors for investigation of miRNA function in vivo and in hard-to-transfect cell types. Our work has brought attention to the use of lentivirally delivered shRNAs as a novel platform for target validation in human disease with particular focus on cytokine targeting and biomedical studies of chronic inflammatory disease. With our current techniques, we are able to potently and specifically target miRNAs based on expression of designed small RNA inhibitors, allowing managing of miRNAs for in vivo purposes. Current interests include miRNA function in the vascular system, inflamed skin, B-cell lymphoma, and as modulators of the innate immune response.

RESEARCH INTERESTS
Efficient insertion of transgenes into chromosomal DNA is a fundamental aim in both therapeutic gene transfer and genetic engineering for animal transgenesis. Based on our expertise in gene vector engineering with particular focus on DNA transposon-based technologies and lentiviral vector systems - our scientific interests are diverse and numerous and include creation of hybrid vector technologies, protection against transcriptional silencing, miRNA inhibition, RNA-directed intervention of disease, and development of disease models in transgenic cloned pigs just to mention a few.

Our current research interests include:

Development and use of vectors that combine the beneficial properties of DNA transposons - like the Sleeping Beauty transposon - and lentiviral vectors with particular focus on altering the integration profile of HIV-1-derived vectors.

Studies of the molecular properties of genomic vector insertion sites, potentially related mechanisms of vector silencing, and means of evading transcriptional silencing.

Analysis of the inherent gene-regulatory properties of DNA transposons.

Development of new strategies for vector-based inhibition of miRNAs in vitro and in vivo.

Gene and small RNA transfer to xenotransplanted human skin with particular focus on cytokine and miRNA expression/regulation.

Lentivirus-based gene and small RNA transfer to the vascular system with particular focus on miRNA inhibition in vascular smooth muscle cells of the arterial wall.

Lentiviral gene transfer to B-cells with the purpose of studying gene and miRNA functions in B-cell lymphoma.

Genetic engineering of transgenic cloned pigs as large animal disease models with emphasis on creation of transgenic pigs with genetic predisposition for development of chronic skin inflammation and atherosclerosis. In addition, we are exploring site-directed engineering approaches and genetic sensoring systems for use in transgenic animals and

METHODOLOGIES
The lab specializes in lentivirus- and DNA transposon-based vector technologies and offer students detailed insight in retrovirology and lentiviral vector production as well as DNA transposon technologies. We are delighted to share these core technologies with collaborators and welcome local collaborations involving lentiviral and/or DNA transposon-directed gene transfer. With the increasing focus on miRNA biology, we offer expertise and education within the field of miRNA-directed gene regulation and has specialized in the use of engineered vector-encoded miRNA inhibitors.

Standard methodologies in the laboratory include plasmid construction/cloning, qPCR, tissue culture, ELISA, fluorescence microscopy, flow cytometry, and DNA, RNA, and protein blotting techniques. Also, our work includes engineering of DNA transposon-based vectors, immunostaining, siRNA screening methods, and viral vector production, purification, and in vivo administration.

COLLABORATORS & Centers

The work in the research group is founded on numerous local, national, and international collaborations. The JGM group was a partner in an EU-consortium (FP6, INTHER) from 2005-08 and has since collaborated with several partners of the consortium and contributed to the creation of a strong network within the field of DNA transposon-based gene transfer technologies in Europe.

The JGM research group is currently a partner in Aarhus Research Center for Innate Immunity (ARCII).

The JGM Lab, July 2011

Research Group Members

Nynne Sharma, PhD student

Rasmus O. Bak, PhD student

Yujia Cai, PhD student

Moslem Ranjbar, PhD student

Lisbeth Dahl Schrøder, technician

Maria do Nascimento Lopes Primo, Master’s student

Anne Kruse Hollensen, Master’s student

Kristian Skipper, Master’s student

Helle Christiansen, Master’s student

Henvendelse om denne sides indhold: 
Revideret 03.08.2016