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Faculty Detail Faculty Entry   
Name RALPH D SANDERSON  
Campus Address WTI 602B Zip 0007
Phone 205-996-6226
E-mail sanderson@uab.edu" id="FacultyDetail1EmailAddress"><a href="mailto:sanderson@uab.edu">sanderson@uab.edu</a>
URL
 
 

Department Affiliations(s)
Appointment Type Department Division Rank
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Center for Metabolic Bone Disease  Center for Metabolic Bone Disease Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Primary  Pathology   Joint Pathology Professor

Biographical Sketch 
Dr. Sanderson received his PhD degree in Cell Biology in 1986 from the University of Alabama at Birmingham (Advisor, Richard Mayne) followed by a postdoctoral fellowship in the laboratory of Merton Bernfield at Stanford University. He joined the faculty in Pathology at the University of Arkansas for Medical Sciences in 1989 and rose to the rank of Professor in 2000. There, he held the Drs. Mae and Anderson Nettleship Chair in Oncologic Pathology and also served as Director of Basic Research for the Arkansas Cancer Research Center. He joined the UAB Department of Pathology in 2006 and is the UAB Endowed Professor in Cancer Pathobiology.

Society Memberships
Organization Name Position Held Org Link
American Association for Cancer Research    http://www.aacr.org/ 
American Association for the Advancement of Science    http://www.aaas.org/ 
American Society for Biochemistry and Molecular Biology    http://www.asbmb.org/ 
American Society for Matrix Biology  Council Member  http://www.asmb.net/ 
International Society for Extracellular Vesicles    http://www.isev.org/ 
Metastasis Research Society    http://www.metastasis-research.org/ 
 

Research/Clinical Interest
Title
Molecular Regulation of the Tumor Microenvironment
Description
The tumor microenvironment has emerged as a major regulator of tumor growth and progression. The long-term goal of the Sanderson lab is to determine how tumor-stromal interactions mediated by heparan sulfate and the enzyme heparanase regulate the tumor microenvironment and to use that knowledge to design new cancer therapies. We have shown that heparan sulfate proteoglycans and heparanase promote tumor growth and metastasis of multiple myeloma and breast tumors, two tumors that home to and grow within bone. Our hypothesis is that heparan sulfate drives tumor growth by concentrating heparin-binding growth factors (e.g., FGF-2, VEGF, HGF) within the tumor microenvironment and promoting interactions of these growth factors with their high affinity receptors. Thus, interfering with heparan sulfate function has the potential to attenuate numerous signaling pathways important in tumor growth and metastasis. Our current experimental focus is two-fold. First, we are examining how enzymes that modify heparan sulfate such as heparanase within the microenvironment alters tumor behavior and promotes an aggressive tumor phenotype. We have recently discovered that this occurs, at least in part, via heparanase regulation of tumor secreted exosomes. These small vesicles contain proteins and nucleic acids that can be transferred horizontally to other cells within the tumor microenvironment and beyond and thus act as important mediators of intercellular communication. Second, we are developing novel heparanase inhibitors and testing them as potential anti-cancer drugs. One of these recently has entered clinical trials in myeloma patients. This work will lead to a better understanding of the tumor microenvironment and how it can be disrupted to block tumor growth. Our work is currently funded by four NIH grants and a grant from the United States - Israel Binational Science Foundation.

Postdoc Positions Available
Date Posted Position Title
No records
 

Selected Publications 
Publication PUBMEDID
Ramani, V. C., Purushothaman, A., Stewart, M. D., Thompson, C. A., Vlodavsky, I., Au, J. L., and Sanderson, R. D. (2013) The heparanase/syndecan-1 axis in cancer: mechanisms and therapies. FEBS J In press
 		 23374281 
Thompson, C. A., Purushothaman, A., Ramani, V. C., Vlodavsky, I., and Sanderson, R. D. (2013) Heparanase regulates secretion, composition and function of tumor cell-derived exosomes. J. Biol. Chem. In press. Selected as a JBC Paper of the Week.
 		 23430739 
Purushothaman, A., Babitz, S. K., and Sanderson, R. D. 2012. Heparanase enhances the insulin receptor signaling pathway to activate extracellular signal-regulated kinase in multiple myeloma. J. Biol. Chem. 287:41288-41296.  23048032 
Ramani, V.C., Pruett, P.S., Thompson, C.A., Delucas, L.D. and Sanderson, R.D. 2012. Heparan sulfate chains of syndecan-1 regulate ectodomain shedding. J. Biol. Chem. 287:9952-61.   22298773 
Purushothaman, A., Hurst, D.R., Pisano, C., Mizumoto, S., Sugahara, K. and Sanderson, R.D. 2011. Heparanase-mediated loss of nuclear syndecan-1 enhances histone acetyltransferase (HAT) activity to promote expression of genes that drive an aggressive tumor phenotype. J. Biol. Chem. 286:30377-83.   21757697 
Ritchie, J.P., Ramani, V.C., Ren, Y., Naggi, A., Torri, G., Casu, B., Penco, S., Carminati, P., Tortoreto, M., Zunino, F., Vlodavsky, I. Sanderson, R.D. and Yang, Y. 2011. SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis. Clin. Cancer Res. 17:1382-93.  21257720 
Ramani, V.C., Yang, Y., Ren, Y., Nan, L. and Sanderson, R.D.* 2011. Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity. J. Biol. Chem. 286:6490-99. * Selected as a J. Biol. Chem. JBC Paper of the Week & JBC Paper of the Year.  21131364 
Barash, U., Cohen-Kaplan, V., Dowek, I., Sanderson, R.D., Ilan, N., Vlodavsky, I. 2010. Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis. FEBS J. 277(19):3890-903.  20812981 
Yang, Y., Ren, Y., Ramani, V.C., Nan, L., Suva, L.J., Sanderson, R.D. 2010. Heparanase enhances local and systemic osteolysis in multiple myeloma by upregulating the expression and secretion of RANKL. Cancer Res. 70:8329-8338.  20978204 
Sanderson, R.D. and Epstein, J. 2009. Myeloma bone disease. J. Bone Miner. Res. 24(11):1783-8.   19839769 
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Keywords
tumor, microenvironment, cancer, heparan sulfate, proteoglycan, heparanase, exosomes, metastasis, bone, myeloma, breast cancer, drug resistance

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