& Obstetrics, Gynecology & Reproductive Sciences
Affiliated Scientist Manitoba Institute of Child Health & Centre of Aging
Faculty of Medicine, University of Manitoba
130 Basic Medical Sciences Building
745 Bannatyne Avenue
Winnipeg, Manitoba, Canada, R3E 0J9
Telephone: 1-204-789-3982
Fax: 1-204-789-3920
Email: sabine.hombach@med.umanitoba.ca
ACADEMIC EDUCATION
2004 Habilitation in Anatomy and Reproductive Biology
Martin-Luther-University Halle-Wittenberg, Faculty of Medicine, Halle/Saale, Germany
2003 Board Certificate as “Anatomist” by the German Anatomical Society
and the German Medical Association
2003 Medical specialization in Anatomy by the German Medical Association
1994 Doctoral Degree (Ph.D.)
Justus-Liebig-University Giessen, Germany, Internal Medicine,
Section Pathophysiology
1991 License as Medical Doctor (M.D.)
Justus-Liebig-University of Giessen, Germany
1989 – 1991 Resident in Internal Medicine
University Hospital Bad Hersfeld, Justus-Liebig-University Giessen,
Germany
1982-1989 Studies in Human Medicine (Medical School)
Justus-Liebig-University Giessen, Germany
ACAEMIC HONORS
2009 Murray L. Barr Award
Canadian Association of Anatomy, Neurobiology and
Cell Biology (CAANCB)
2002 Merck European Thyroid von Basedow Research Prize
German Endocrine Society
(Deutsche Gesellschaft für Endokrinologie; DGE)
1998-2000 Post-doctoral Research Fellowship by the Provincial Government of
Saxony-Anhalt, Germany
RESEARCH SUMMARY
My two main research interests are in the field of cancer research.
I study the role of insulin-like members of the relaxin family and cognate receptors in tumor growth, angiogenesis, and tissue invasion/metastasis. My lab discovered the Ca2+-binding protein S100A4, also named metastasin, as a novel relaxin target in human cancer cells. I am identifying the molecular pathways relaxin members utilize to alter the motility and tissue invasiveness of tumor cells, remodel the extracellular tumor matrix, recruit stem cells to become functional residents in tumor sites, and stimulate tumor neoangiogenesis.
The defined local endocrine milieu and alterations in the responsiveness/resistance to endocrine factors can elicit genomic changes that can lead to carcinogenesis. My lab studies early genomic changes during carcinogenesis in an endocrine context using nuclear three-dimensional analysis of telomeres and cytogenetic chromosomal profiling. Further, we study the role of non-histone chromatin binding proteins of the HMGA family, found exclusively in stem cells and many cancer cells, in telomere architecture and resistance to DNA damage in cancer cells and investigate their innovative use in advanced strategies for the treatments of cancer patients.
My research received financial support from: Natural Sciences and Engineering Council (NSERC), Manitoba Health Research Council (MHRC), Manitoba Institute of Child Health (MICH), Manitoba Medical Service Foundation (MMSF), German Research Council (DFG).
Figures 1: We are investigating the mechanisms by which relaxin-like peptides increase cell invasiveness and metastasis in thyroid cancer. (A) Blood vessel formation (CD31 immunohistochemistry) in a nude mouse xenograft model for thyroid cancer growths. (B) in-vitro angiogensis tube formation assay after stimulation of HUVEC cells with relaxin. Phalloidin staining of the actin cytoskeleton in empty vector controls (C) and S100A4 transfectants (D) of C643 thyroid carcinoma cells. Image of a culture of primary thyroid carcinoma cells from a patient with papillary thyroid carcinoma (E).
Figures 2: We are investigating changes in the 3D telomere profiles during the development of endometrial cancer using a PTEN +/- mouse model. The images dhow a cancerous endometrial gland: (A) HE staining, (B) PTEN imunohistochemistry, and (C) Dapi stain of nuclei. (E) shows the telomere staining after in-situ hybridization with a Cy3 PNA telomere probe (red dots), nucleus is stained with Dapi (blue). (D) We determine the 3D telomere architecture of telomeres within a single interphase nuceus using TeloViewTM software (Vermolen et al., Cytometry A, 2005)
Figures 3: We study distinct genomic changes in antiestrogen resistant human breast cancer cells with acquired resistance to tamoxifen or ICI182.780 using 3D telomere-FISH. Images of MCF-7 human breast cancer cells: Fluorescence image (A) of telomeres (red signals) within an interphase nucleus (A), and 3D rendered image of the telomere architecture (B). Telomere hybridization signals in a metaphase spread of MCF-7 cells (C).
For a list of my publication please link to the PubMed website:
http://www.ncbi.nlm.nih.gov/PubMed/ and search for “Hombach-Klonisch”
TEACHING
Anatomy is of fundamental importance in all health-associated disciplines. I am teaching Gross Anatomy, Histology, and Neuroanatomy to students of several health-related disciplines, including Medicine (years I, II, and IV). In my teaching I focus on Clinical Anatomy. I emphasize the link between structure and function at the level of the whole body, tissues, cells, and at the molecular level. It is this knowledge of structure-function relationships that I consider essential in understanding the underlying mechanisms in disease development and progression.
With the increasing utilization of radiological imaging techniques in medical practise, it is crucial for students to comprehend structural and topographical Anatomy in 3 dimensions. The classical cadaveric dissection in combination with cross-sectional anatomy teaching is invaluable to study the topography and appreciate the individual differences thereof.
I have recently engaged in creating 3D virtual anatomy models of body regions, such as the head, to visualize deep anatomical structures in a non-destructive way. This work is done in collaboration with the Depts. of Radiology (Dr. Goertzen) and Surgery (Dr. Hochman) and the Virtual Reality Centre (Myron Semegen), Industrial Technology Centre (ITC), in Winnipeg.
Funding for this project on 3D Anatomy virtual models was received from the Virtual Reality Applications Fund (VRAF), ITC, and from the Dean’s Strategic Research Fund (DSRF) of the Faculty of Medicine, University of Manitoba.
Figure 4: 3D virtual Anatomy models created from CT scans of a male human head: (A) bones of the nasal cavity, (B) eyes with muscles and optic nerves, (C) skull with muscles of mastigation, and (D) internal carotid and vertebral arteries contributing to the circle of Willis.
