Simone Hettmer, MD

Research Overview

Soft-tissue sarcomas are a heterogeneous group of cancers arising in non-hematopoietic, mesodermal tissues. These tumors can occur at any age, but many sarcomas are disproportionately common in children and adolescents (e.g. rhabdomyosarcoma, or RMS, the most common soft-tissue sarcoma in children and adolescents). With currently available, risk-adapted, multimodal therapy, RMS survival ranges from >90% in patients with low-risk disease to <10% in patients with highest-risk metastatic tumors. Unfortunately, RMS cure, even for low risk patients, comes at an extremely high price in terms of life-long functional deficits, organ toxicities and secondary cancers due to treatment sequelae, not infrequently amplified by an underlying cancer predisposing condition. Conversely, at the other end of the disease spectrum, most patients with high-risk metastatic RMS die of disease despite intensive therapy, and, sadly, their outcomes have not improved for decades. My research is based on the premise that: (i) establishing novel, effective anti-sarcoma therapeutic strategies is a critical challenge in pediatric oncology, and (ii) skeletal muscle as a site of origin for sarcomas with and without myogenic differentiation is a well-studied and easily accessible tissue compartment in mice. My postdoctoral work has established a new, highly tractable strategy to induce mouse sarcomas in which sarcoma-associated genetic lesions can be introduced directly into discrete, muscle-resident myogenic and mesenchymal cell lineages to examine the cellular basis for histopathological variation among sarcomas. I have used this platform to highlight the importance of Ras pathway activation in sarcomas and identify a set of potentially actionable downstream targets for further validation. My ongoing research focuses on the use of mouse models of sarcoma in skeletal muscle in order to distinguish biologically distinct sarcoma categories and to validate actionable downstream cellular pathways as potential new anti-sarcoma therapeutic targets. Other areas of active research include studies aimed at delineating the cellular heterogeneity of normal skeletal muscle and generating primary humanized sarcoma xenografts.

About Simone Hettmer

Simone Hettmer received an MD from the University of Tuebingen in Germany. She completed a research fellowhip at Children’s Research Institute in Washington D.C. She completed internship and residency at the Massachusetts General Hospital and a fellowship in pediatric hematology/ oncology at Children's Hospital Boston/Dana-Farber Cancer Institute. She currently is a post-doctoral research fellow in the laboratory of Dr. Amy Wagers.

Key Publications

• S Hettmer, J Liu, CM Miller, MC Lindsay, CA Sparks, DA Guertin, RT Bronson, DM Langenau, AJ Wagers. Sarcomas induced in discrete subsets of prospectively isolated mouse skeletal muscle cells. Proc. Natl Acad Sci., U.S.A.; 2011; 108(50): 20002-7.

• KY Tan, S Eminli, S Hettmer, K Hochedlinger, AJ Wagers. Efficient generation of iPS cells from skeletal muscle stem cells. PLOS One. 2011; 6(10): e26406.

• S. Hettmer, A.Wagers. Rhabdomyosarcoma masquerading as acute leukemia: the quest for cell-of-origin. Nature Medicine. 2010:16(2):171-3.

• S Hettmer, S Ladisch, K Kaucic. Low complex ganglioside expression characterizes human neuroblastoma cell lines. Cancer Letters. 2005; 225(1): 141-149.

• S Hettmer, L Dannecker, J Foell, MW Elmlinger, GE Dannecker. Effects of insulin-like growth factors and insulin-like growth factor binding protein-2 on the in vitro proliferation of peripheral blood mononuclear cells. Human Immunology. 2005; 66(2): 95-103.

• S Hettmer, R McCarter, S Ladisch, K Kaucic. Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid. British Journal of Cancer. 2004; 91(2): 389 - 397.

• S Hettmer, C Frey, W Woods, S Ladisch, K Kaucic. Biological stratification of human neuroblastoma by complex "b" pathway ganglioside expression. Cancer Research. 2003; 63(21): 7270-7276.

• M Weiss, S Hettmer, P Smith, S Ladisch. Inhibition of melanoma tumor growth by a novel inhibitor of glucosylceramide synthase. Cancer Research. 2003; 63(13): 3654-3658.

Related Labs/Links

Simone Hettmer is a post-doctoral fellow in the lab of Dr. Amy Wagers, PhD.