Regents Professor, Department of Pediatrics, and Pediatric Blood and Marrow Transplant (BMT) Center
Dr. Blazar's lab is undertaking research in the following areas:
2. Improving murine and human regulatory T cell potency in suppressing inflammatory responses. Regulatory T cells will be directed homing to sites of inflammation using gene editing and gain- and loss- of function techniques. Studies include miRNA-RNA analyses and gain-and-loss of function including use of antagomirs. Potency will be increased by regulating signaling and structural pathways.
3. Transcriptional regulation by gain-and-loss of function studies in human T cells reprogrammed into induced pluripotent stem cells (IPSCs) that are redifferentiated into various types of T cell populations. Such studies include gene editing of IPSCs. Epigenetic changes will be monitored to identify new regulatory controls on T cell subsets.
4. High throughput screening of human induced pluripotent stem cells (IPSCs) using runx1 reporter knockin constructs.This project will identify master regulators of definitive human hematopoiesis.
Executive Vice Dean, Medical School
Distinguished McKnight Professor, Department of Pediatrics
Director, Stem Cell Institute
Edmund Wallace Tulloch and Anna Marie Tulloch Chair, Stem Cell Biology, Genetics and Genomics
Jakub Tolar's research focuses on using stem cell biology and genome engineering to provide therapies for incurable genetic disorders like epidermolysis bullosa (EB), Hurler syndrome, dyskeratosis congenita, and Fanconi anemia. This research is a logical outgrowth of his specific expertise in stem cell therapy and his primary goal of developing patient- and genetic disease-specific therapies that are safe and effective.
As director of the University of Minnesota Stem Cell Institute, he builds on many years of basic science work in stem cell gene therapy and many years of clinical experience with children born with genetic disorders. He has extensive knowledge of the biology of genome engineering and transplantation of stem cells (MSCs, iPSCs, hematopoietic and non-hematopoietic bone marrow, and cord blood cells). This work is supported by his excellent laboratory staff and facilities. His laboratory group has successfully generated induced pluripotent stem cells (iPSCs, embryonic stem cell equivalents derived from adult differentiated cells) from patients with Fanconi anemia and with the two most severe genodermatoses: recessive dystrophic EB and junctional EB. They have further differentiated these iPSCs to produce both keratinocytes and hematopoietic progenitor cells. They recently performed the seamless, transgene-free gene editing of a mutant collagen gene in the natural genomic context of iPSCs from a patient with EB, the first time this has been done in any human genetic disease. Current efforts focus on the next generation of safer gene therapy, genome editing with transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9.
Presentation captured from Oct. 20th CGE Meeting.
FEATURED PHD STUDENT:
About the CGE:
Advances in DNA sequencing technology have made it possible to identify the many genes within an organism’s genome. Two current challenges are to understand how these genes work together to dictate how an organism grows and develops and how to make changes in genomes for medical and commercial purposes. Meeting these challenges requires sophisticated tools to manipulate genes. The mission of the Center for Genome Engineering is to develop and disseminate the tools that enable efficient, responsible genome engineering.
At the heart of the CGE’s genome engineering technology are transposable elements – segments of DNA capable of changing their chromosomal position or moving from one DNA molecule to another. Transposable elements constitute a large portion of DNA in many organisms. They naturally shape the genetic code by causing mutations, rearrangements and sequence duplications. At the Center for Genome Engineering, scientists are harnessing these naturally occurring genome engineers to enable precise changes to the genetic code.
We are excited by the progress of the Center since its establishment in 1999 and by the many discoveries of Center scientists that enable new approaches to genome engineering. The Center is poised for the next decade of discovery and is ready to implement its technologies to solve real world problems.