Molecular Physiology

Our Research

Where do the roads of normal and tumor development converge?
The sympathetic nervous system (SNS) derives from neural crest, a transient stem cell population during vertebrate embryogenesis. The neural crest is remarkable in its ability to differentiate into diverse cell types including cartilage, glia, neuronal cells of the SNS and chromaffin cells. Incorrect embryonic development can lead to neural crest derived cristopathies, including cancer. We aim to understand the function of SNS related proteins in cancer and the function of cancer related proteins in SNS development.

Childhood tumor form neuroblastoma as well as paragangliomas and pheochromocytomas (PPGLs) derive from neural crest sharing a common ancestor cell. Neuroblastoma is a tumor of infancy, being the most common tumor form in children less than 1 year. The majority of patients are diagnosed before the age of 5 and there are rare cases where children are born with their tumor. Tumor formation, or priming, thus occur already during embryogenesis. While the overall survival rate of neuroblastoma has steadily and impressively increased during the last decades there is a fraction of patients diagnosed with high-risk tumors presenting with dismal prognosis. PPGLs are slow-growing neuroendocrine tumors and there are virtually no treatment options for patients with metastases. We are establishing embryonic models using the chick embryo and human induced pluripotent stem cells to mimic the environment when these tumors are formed.

Aims

• To unravel how trunk neural crest specific genes can function as driver genes in cancer
• To elucidate the role of cancer associated proteins, including HIF-2a, in neural crest development and their potential role in tumor onset 
• Develop models for normal neural crest and tumor initiation using chick embryos and human induced pluripotent stem cells

Impact

Cancer patients, including children, mainly die from organ failure as a consequence of metastatic disease. It is clear that early detection and thus early treatment correlate to improved outcome, better response to therapy and less metastatic spread. We seek diagnostic markers and the possibility to treat at early stages by pinpointing genes that are specific to both tumor and neural crest cells. Basic research of tumor initiation and progenitor cell migration indeed lay the foundation for these clinical implications.

Team

Sofie Mohlin

Principal Investigator, Sofie [dot] Mohlin [at] med [dot] lu [dot] se (Sofie[dot]Mohlin[at]med[dot]lu[dot]se)

Niklas Engström

Laboratory Engineer, Niklas [dot] Engstrom [at] med [dot] lu [dot] se (Niklas[dot]Engstrom[at]med[dot]lu[dot]se)

Marina Mazariegos León

Laboratory Engineer, %20marina [dot] mazariegos [at] med [dot] lu [dot] se (marina[dot]mazariegos[at]med[dot]lu[dot]se)

Perrine Burdeyron

Postdoc, perrine [dot] burdeyron [at] med [dot] lu [dot] se (perrine[dot]burdeyron[at]med[dot]lu[dot]se)

Tomas Gregor

Postdoc, Tomas [dot] Gregor [at] med [dot] lu [dot] se (Tomas[dot]Gregor[at]med[dot]lu[dot]se)

Sinan Karakaya

Postdoc, Sinan [dot] Karakaya [at] med [dot] lu [dot] se (Sinan[dot]Karakaya[at]med[dot]lu[dot]se)

Elina Fredlund

PhD student, Elina [dot] Fredlund [at] med [dot] lu [dot] se (Elina[dot]Fredlund[at]med[dot]lu[dot]se)

Stina Andersson

PhD Student, Stina [dot] Andersson [at] med [dot] lu [dot] se (Stina[dot]Andersson[at]med[dot]lu[dot]se)

Anja Zethraeus

Student, anja [dot] zethraeus [at] med [dot] lu [dot] se (anja[dot]zethraeus[at]med[dot]lu[dot]se)