Stem cells to red blood cells

Our Research

84% of all cells in our bodies are red blood cells. Today many anemic patients suffer from inefficient production of these essential cells. We believe safer and more effective therapies can be developed based on advances in understanding the process of red cell production.

To understand the developmental process of red blood cell formation:

My group became the first to demonstrate direct lineage reprogramming of fibroblasts to red blood cell and megakaryocyte progenitors, two findings that define the genetic instructions for these two cell types important in transfusion medicine.

Through analysis of genome wide association studies and screening my group has identified several previously unknown genes that are essential for normal red cell production. These genes are currently studied in knockout mice and human systems to determine their molecular roles in erythropoiesis. Importantly some of these genes regulate hemoglobin synthesis and proliferation of erythroblasts.

To develop novel therapies for patients with anemia that today lack effective therapy:

From different screening and medicinal chemistry approaches we today have several promising drug candidates for treatment of anemia that are validated in anemic mouse models and on cells from patients with severe anemia. We are particularily focusing on developing therapies for patients with severe congenital disorder Diamond-Blackfan Anemia, where we in addition to small molecule therapy want to develop clinical gene therapy.

Aims

• To identify key intrinsic and extrinsic regulators of red blood cell progenitor development and homeostasis.
• To discover and develop novel therapies for bone marrow failure and anemia.

Impact

Our research program tackles important challenges at the frontier of our field, with potential for long-lasting impact on the medical care of patients that today lack safe and efficient therapies. Increased insight and control over red blood cell fate fills an important gap in understanding erythroid fate determination with implications for red blood cell-related research and therapy. Disease-specific and first-in-class drugs are developed and studied in collaboration with companies and hospitals in order to enable translation into the clinic treatment of bone marrow failure and anemia. Some of these therapies also have potential for cancer and bone disorders.

List of Team Flygare's publications

Team

(name linked to profile in Lund University research portal)

Johan Flygare

Principal Investigator, Johan [dot] Flygare [at] med [dot] lu [dot] se (Johan[dot]Flygare[at]med[dot]lu[dot]se) 

Kiyoka Saito

Postdoc, Kiyoka [dot] Saito [at] med [dot] lu [dot] se (Kiyoka[dot]Saito[at]med[dot]lu[dot]se)

Abdul Ghani Alattar 

Research Engineer, Abdul_Ghani [dot] Alattar [at] med [dot] lu [dot] se (Abdul_Ghani[dot]Alattar[at]med[dot]lu[dot]se) 

Jun Chen 

Research Engineer, Jun [dot] Chen [at] med [dot] lu [dot] se (Jun[dot]Chen[at]med[dot]lu[dot]se) 

Alexander Mattebo 

PhD student, Alexander [dot] Mattebo [at] med [dot] lu [dot] se (Alexander[dot]Mattebo[at]med[dot]lu[dot]se) 

Gustav Sundén

PhD student, Gustav [dot] Sunden [at] med [dot] lu [dot] se (Gustav[dot]Sunden[at]med[dot]lu[dot]se)