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Faculty Detail    
Name RALPH D SANDERSON
  
Campus Address VH G038 Zip 3300
Phone
E-mail  ralphsanderson@uabmc.edu
Other websites UAB Scholars
     

Education
Undergraduate  University of Alabama    1975  Bachelor of Science with Honors 
Graduate  University of Alabama at Birmingham    1986  PhD Anatomy and Cell Biology 
Fellowship  Stanford University    1989  Biological Chemistry 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Joint Pathology  Molecular & Cellular Pathology Professor Emeritus

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

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 currently is the Director of the Division of Molecular and Cellular Pathology.

Society Memberships
Organization Name Position Held Org Link
American Association for Cancer Research    http://www.aacr.org/ 
American Society for Matrix Biology    http://www.asmb.net/ 
International Society for Extracellular Vesicles    http://www.isev.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-host cell 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 alter 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. 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 the National Institutes of Health.

Selected Publications 
Publication PUBMEDID
Karamanos N.K., Piperigkou, Z., Theocharis, A.D., Watanabe, H., Franchi, M., Baud, S., Brezillon, S., Gotte, M., Passi, A., Vigetti, D., Ricard-Blum, S., Sanderson, R.D., Neill, T. and Iozzo, R.V. 2018. Proteoglycan chemical diversity drives multifunctional cell regulation and therapeutics. Chem Rev 118:9152-9232.   30204432 
Bandari, S.K., Purushothaman, A., Ramani, V.C., Brinkley, G.J., Chandrashekar, D.S., Varambally, S., Mobley, J.A., Zhang, Y., Brown, E.E., Vlodavsky, I. and Sanderson, R.D. 2018. Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior. Matrix Biol. 65:104-118.  28888912 
Sanderson, R.D., Elkin, M., Rapraeger, A.C., Ilan, N. and Vlodavsky, I. 2017. Heparanase regulation of cancer, autophagy and inflammation: New mechanisms and targets for therapy. FEBS J. 284:42-55.  27758044 
Bandari, S.K., Tripathi, K., Rangarajan, S. and Sanderson, R.D. 2020.Therapy-induced chemoexosomes: Sinister small extracellular vesicles that support tumor survival and progression. Cancer Lett. 493:113-119.  32858103 
Ramani, V. C., Vlodavsky, I., Ng, M., Zhang, Y., Barbieri, P., Noseda, A., and Sanderson, R. D. 2016. Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype. Matrix Biol. 55:22-34.  27016342 
Ramani, V.C., Zhan, F., He, J., Barbieri, P., Noseda, A., Tricot, G. and Sanderson, R.D. 2016. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma. Oncotarget. 7:1598-1607.   26624982 
Purushothaman, A., Bandari, S.K., Liu, J., Mobley, J.A., Brown, E.E. and Sanderson, R.D. 2016. Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions. J. Biol. Chem. 291:1652-63.   26601950 
Stewart, M.D., Ramani, V.C. and Sanderson, R.D. 2015. Shed Syndecan-1 Translocates to the Nucleus of Cells Delivering Growth Factors and Inhibiting Histone Acetylation: A novel mechanism of tumor-host crosstalk. J. Biol. Chem. 290:941-949.  25404732  
Amin, R., Tripathi, K., and Sanderson, R.D. 2020. Nuclear heparanase regulates chromatin remodeling, gene expression and PTEN tumor suppressor function. Cells 9. doi: 10.3390/cells9092038  32899927 
Vlodavsky, I., Ilan, N. and Sanderson, R.D. 2020. Forty Years of Basic and Translational Heparanase Research. In: Vlodavsky I., Sanderson R., Ilan N. (eds) Heparanase. Adv. Exp. Med. Bio.1221:3-59.  32274705 
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. 288:10093-10099 Selected as a JBC Paper of the Week and JBC "Best of 2013."
 		 23430739 
Tripathi, K., Ramani, V.C., Bandari, S.K., Amin, R., Brown, E.E., Ritchie, J.P., Stewart, M.D. and Sanderson, R.D. 2020. Heparanase promotes myeloma stemness and in vivo tumorigenesis. Matrix Biol., 88:53-68.  31812535 
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 280:2294-306
 		 23374281 
Galli, M., Chatterjee, M., Grasso, M., Specchia, G., Magen, H., Einsele, H., Celeghini, I., Barbieri, P., Paoletti, D., Pace, S., Sanderson, R.D., Rambaldi and Nagler, A. 2018. Phase I study of the heparanase inhibitor roneparstat: an innovative approach for multiple myeloma therapy. Haematologica 103:e469-e472.   29700168 
Purushothaman A. and Sanderson R.D. 2020. Heparanase: A Dynamic Promoter of Myeloma Progression. In: Vlodavsky I., Sanderson R., Ilan N. (eds) Heparanase. Adv. Exp. Med. Bio.1221:331-349  32274716 
Tripathi, K., Ramani, V.C., Bandari, S.K., Amin, R., Brown, E.E., Ritchie, J.P., Stewart, M.D. and Sanderson, R.D. (2020) Heparanase promotes myeloma stemness and in vivo tumorigenesis. Matrix Biol., 88:53-68  31812535 
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 and JBC "Best of 2011."  21131364 
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 
Purushothaman, A., Uyama, T., Kobayashi, F., Yamada, S., Sugahara, K., Rapraeger, A.C., Sanderson, R.D., 2010. Heparanase enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood. 115:2449-57.  20097882 
Yang, Y., MacLeod, V., Dai, Y., Khotskaya-Sample, Y., Shriver, Z., Venkataraman, G., Sasisekharan, R., Naggi, A., Torri, G., Casu, B., Vlodavsky, I., Suva, L.J., Epstein, J., Yaccoby, S., Shaughnessy, J.r., J.D., Barlogie, B., and Sanderson, R. 2007. The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy. Blood 110:2041-48.  17536013 
Yang, Y., Macleod, V., Miao, H.Q., Theus, A., Zhan, F., Shaughnessy, J.D., Jr., Sawyer, J., Li, J.P., Zcharia, E., Vlodavsky, I., and Sanderson, R.D. 2007. Heparanase enhances syndecan-1 shedding: A novel mechanism for stimulation of tumor growth and metastasis. J Biol Chem. 282:13326-13333.  17347152 
Kelly, T., Suva, L.J., Huang, Y., Macleod, V., Miao, H.Q., Walker, R.C., and Sanderson, R.D. 2005. Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases. Cancer Res 65:5778-5784.
 		 15994953 
Yang, Y., Macleod, V., Bendre, M., Huang, Y., Theus, A.M., Miao, H.Q., Kussie, P., Yaccoby, S., Epstein, J., Suva, L.J., Kelly, T., and Sanderson, R.D. 2005. Heparanase promotes the spontaneous metastasis of myeloma cells to bone. Blood 105:1303-1309.
 		 15471949 
 

Keywords
tumor, microenvironment, cancer, heparan sulfate, proteoglycan, heparanase, exosomes, metastasis, bone, myeloma, breast cancer, drug resistance