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Stem Cell Regulators

Larsson group

Our research

The focus of the research in the Larsson group is to define genes and pathways that regulate human hematopoietic stem cells (HSCs) and to develop novel strategies for ex vivo stem cell expansion to enhance current cell therapies of hematological disorders. Over the last few years the laboratory has developed strategies to screen for modifiers of self-renewal/proliferation in primary human hematopoietic stem- and progenitor cells (HSCPs) using complex viral vector libraries expressing shRNA. Previous work in the lab has demonstrated the feasibility of pooled shRNA screens in conjunction with next generation sequencing to identify genes and pathways that regulate primary human stem cell populations. A major focus is now to further develop the screening paradigms by implementing the CRISPR/Cas9 system to target human HSPCs. The goal is to develop robust GMP compatible conditions for HSC expansion that can be exploited in clinical transplantation settings and in the future facilitate gene editing of HSCs or the derivation of transplantable HSCs from ES/iPS cells.

Aims

  • To screen primary human HSCs for novel modifiers of self-renewal and differentiation using shRNA and CRISPR/Cas9 lentiviral libraries
  • To develop ex vivo HSC expansion strategies by targeting candidate genes from the screens in human HSCs
  • To study functional and mechanistic aspects of novel candidate genes in both normal and malignant hematopoiesis

Impact

Our studies involve novel and innovative approaches to tackle the long-standing challenge of ex vivo HSCs expansion. By applying modern techniques and strategies to study both normal and malignant HSCs we will unravel genes and pathways that govern their growth and self-renewal. Successful development of strategies for expansion of HSCs could enable curable HSC transplantation for large numbers of patients with hematological malignancies currently non-eligible for transplantation therapy. This would further address current challenges to generate transplantable HSCs from ES and iPS cells and development of HSC gene therapy applications for inherited hematological disorders. The work may further advance our understanding of leukemia development and regulation of leukemic stem cells and could pave the way for new and more specific therapeutic options.

List of Team Larsson's publications


Team

(name linked to profile in Lund University research portal)

Jonas Larsson 

Principal investigator, MD, PhD, Associate Professor
Jonas [dot] Larsson [at] med [dot] lu [dot] se 

Roman Galeev

Postdoc, roman [dot] galeev [at] med [dot] lu [dot] se 

Natsumi Miharada 

Postdoc, natsumi [dot] miharada [at] med [dot] lu [dot] se 

Mehrnaz Safaee 

Postdoc, mehrnaz [dot] safaee_talkhoncheh [at] med [dot] lu [dot] se 

Agatheeswaran Subramaniam 

Postdoc, Agatheeswaran [dot] Subramaniam [at] med [dot] lu [dot] se

Alexandra Bäckström

PhD student,

Ludwig Schmiderer 

PhD student, ludwig [dot] schmiderer [at] med [dot] lu [dot] se 

David Yudovich 

PhD student, david [dot] yudovich [at] med [dot] lu [dot] se 

Kristijonas Zemaitis

PhD student, Kristijonas [dot] Zemaitis [at] med [dot] lu [dot] se

Ineke De Jong

Research Engineer, ineke [dot] de_jong [at] med [dot] lu [dot] se

Anna Rydström 

Research Engineer, anna [dot] rydstrom [at] med [dot] lu [dot] se 


Co-supervision:

Els Mansell

Postdoctoral Fellow (Enver group), Els [dot] Mansell [at] med [dot] lu [dot] se

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