University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Steven D. Rosen, PhD

Steven D. Rosen, PhD

Professor and Vice-Chair, Department of Anatomy, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

I have a longstanding interest in glycobiology and biological sulfation. The origin of this interest began 30 years ago with our investigation of molecular mechanisms involved in lymphocyte homing to lymph nodes. Our early experiments established that lymphocyte attachment to high endothelial venules in lymph nodes involves a calcium-dependent lectin-like receptor and carbohydrate-based ligands displayed on HEVs. We cloned the receptor, now known as L-selectin, and found a C-type lectin domain, thus confirming its lectin nature. We identified the HEV-ligands biochemically and showed that they contain 6-sulfo sialyl Lewis x as an essential recognition determinant for L-selectin binding. We subsequently identified the critical sulfotransferases within HEVs that elaborate the essential sulfation modifications of the ligands. HEVs with the same biochemical phenotype as in lymph nodes are also found in tertiary lymphoid organs (TLOs) that are associated with tumors. The presence of HEVs in tumor-associated TLOs is correlated with good outcomes for patients with breast cancer and melanoma, probably reflecting immunoprotection by the TLOs that are in proximity to the tumors.
Most recently, we have studied the involvement of autotaxin in lymphocyte homing. We showed that this extracellular enzyme (lysophospholipase D activity) is highly expressed in lymph node HEVs. Here, it produces extracellular lysophosphatidic acid, which stimulates the motility of lymphocytes and promotes their transendothelial migration across HEVs. The action of autotaxin constitutes a novel step in the multistep lymphocyte homing cascade. Autotaxin is frequently overexpressed in human tumors. There is considerable evidence that the enzyme regulates the motility of tumor cells and promotes their metastasis. The SULFs (SULF1 and SULF2) represent an extension of my interest in the regulation of sulfation at the cell surface. We cloned the human versions of these enzymes over 12 years ago. These enzymes are secreted act as neutral pH glucosamine 6-O-endosulfatases for heparan sulfate (HS) chains. By removing 6OS groups from glucosamine in HS chains, the SULFs mobilize growth factors/morphogens from HS sequestration and modulate multiple signaling pathways in the cells.
Over the past 12 years, we have been focusing on the role of the SULFs in cancer, triggered by our finding that one or both SULFs are commonly overexpressed in cancers. Following our initial studies of the SULFs in breast cancer and pancreatic cancer, we have focused on the study of these enzymes in non-small cell lung cancer (NSCLC). Our studies have documented widespread overexpression of SULF2 protein in human NSCLC tumors. Employing a series of tumorigenic lung cancer cell lines, we showed that SULF2 promotes the malignant properties of these cells in both in vitro and vivo assays, including the formation of xenograft tumors in nude mice. We have developed a very sensitive ELISA for SULF2 and have detected the enzyme in human blood. Current studies are directed at determining whether the SULFs could serve as cancer biomarkers in blood or other body fluids.


University of California, Berkeley, CA, B.A., 1966, Physics
Cornell University, Ithaca, NY, Ph.D., 1972, Neurobiology
University of California, San Diego, CA, Postdoc, 1972-76, Cell Biology

Professional Experience

  • 1976-1982
    Assistant Professor, University of California, Anatomy
  • 1982-1986
    Associate Professor of Anatomy, University of California, San Francisco
  • 1987-present
    Professor of Anatomy, University of California, San Francisco
  • 1989-present
    Member, Program in Immunology, UCSF
  • 1992-present
    Member, Biomedical Sciences Program, UCSF
  • 1999-present
    Investigator, Cardiovascular Research Institute, UCSF
  • 2000-present
    Program Member, Comprehensive Cancer Center, UCSF
  • 2001-present
    Member, Steering Committee, NIH Consortium for Functional Glycomics
  • 2005-present
    Vice-Chair and Executive Committee, Dept of Anatomy

Honors & Awards

  • Phi Beta Kappa
  • American Cancer Society Postdoctoral Fellowship
  • Phi Kappa Phi
  • NIH Career Development Award
  • 1993
    Feulgen Lecture
  • 2005
    Keynote address to Keystone Symposium on Complex Carbohydrates
  • 1996-2006
    NIH Merit Award

Selected Publications

  1. Flowers SA, Zhou X, Wu J, Wang Y, Makambi K, Kallakury BV, Singer MS, Rosen SD, Davidson B, Goldman R. Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck. Oncotarget. 2016 Jul 12; 7(28):43177-43187.
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  2. Singer MS, Phillips JJ, Lemjabbar-Alaoui H, Wang YQ, Wu J, Goldman R, Rosen SD. SULF2, a heparan sulfate endosulfatase, is present in the blood of healthy individuals and increases in cirrhosis. Clin Chim Acta. 2015 Feb 02; 440:72-8.
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  3. Rosen SD, Daneman R. High endothelial venules through a transcriptomics lens. Nat Immunol. 2014 Oct; 15(10):906-8.
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  4. Patnode ML, Bando JK, Krummel MF, Locksley RM, Rosen SD. Leukotriene B4 amplifies eosinophil accumulation in response to nematodes. J Exp Med. 2014 Jun 30; 211(7):1281-8.
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  5. Maltseva I, Chan M, Kalus I, Dierks T, Rosen SD. The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair. PLoS One. 2013; 8(8):e69642.
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  6. Patnode ML, Cheng CW, Chou CC, Singer MS, Elin MS, Uchimura K, Crocker PR, Khoo KH, Rosen SD. Galactose 6-O-sulfotransferases are not required for the generation of Siglec-F ligands in leukocytes or lung tissue. J Biol Chem. 2013 Sep 13; 288(37):26533-45.
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  7. Patnode ML, Yu SY, Cheng CW, Ho MY, Tegesjö L, Sakuma K, Uchimura K, Khoo KH, Kannagi R, Rosen SD. KSGal6ST generates galactose-6-O-sulfate in high endothelial venules but does not contribute to L-selectin-dependent lymphocyte homing. Glycobiology. 2013 Mar; 23(3):381-94.
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  8. Lui NS, van Zante A, Rosen SD, Jablons DM, Lemjabbar-Alaoui H. SULF2 expression by immunohistochemistry and overall survival in oesophageal cancer: a cohort study. BMJ Open. 2012; 2(6).
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  9. Zhang Y, Chen YC, Krummel MF, Rosen SD. Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J Immunol. 2012 Oct 15; 189(8):3914-24.
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  10. Phillips JJ, Huillard E, Robinson AE, Ward A, Lum DH, Polley MY, Rosen SD, Rowitch DH, Werb Z. Heparan sulfate sulfatase SULF2 regulates PDGFRa signaling and growth in human and mouse malignant glioma. J Clin Invest. 2012 Mar; 122(3):911-22.
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  11. Lee SM, Rosen S, Weinstein P, van Rooijen N, Noble-Haeusslein LJ. Prevention of both neutrophil and monocyte recruitment promotes recovery after spinal cord injury. J Neurotrauma. 2011 Sep; 28(9):1893-907.
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  12. Arata-Kawai H, Singer MS, Bistrup A, Zante Av, Wang YQ, Ito Y, Bao X, Hemmerich S, Fukuda M, Rosen SD. Functional contributions of N- and O-glycans to L-selectin ligands in murine and human lymphoid organs. Am J Pathol. 2011 Jan; 178(1):423-33.
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  13. Rosen SD, Lemjabbar-Alaoui H. Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate. Expert Opin Ther Targets. 2010 Sep; 14(9):935-49.
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  14. Feng G, Du P, Krett NL, Tessel M, Rosen S, Kibbe WA, Lin SM. A collection of bioconductor methods to visualize gene-list annotations. BMC Res Notes. 2010 Jan 19; 3:10.
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  15. Uchimura K, Lemjabbar-Alaoui H, van Kuppevelt TH, Rosen SD. Use of a phage display antibody to measure the enzymatic activity of the Sulfs. Methods Enzymol. 2010; 480:51-64.
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  16. Hossain MM, Hosono-Fukao T, Tang R, Sugaya N, van Kuppevelt TH, Jenniskens GJ, Kimata K, Rosen SD, Uchimura K. Direct detection of HSulf-1 and HSulf-2 activities on extracellular heparan sulfate and their inhibition by PI-88. Glycobiology. 2010 Feb; 20(2):175-86.
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  17. Rosen SD, Arata-Kawai H. "Home sweet home" for lymphocytes. Blood. 2009 Jul 16; 114(3):499-500.
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  18. Tang R, Rosen SD. Functional consequences of the subdomain organization of the sulfs. J Biol Chem. 2009 Aug 07; 284(32):21505-14.
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  19. Kerr SC, Fieger CB, Snapp KR, Rosen SD. Endoglycan, a member of the CD34 family of sialomucins, is a ligand for the vascular selectins. J Immunol. 2008 Jul 15; 181(2):1480-90.
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  20. Kanda H, Newton R, Klein R, Morita Y, Gunn MD, Rosen SD. Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs. Nat Immunol. 2008 Apr; 9(4):415-23.
    View on PubMed

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