Brad St. Croix, Ph.D.

Brad  St. Croix, Ph.D.
Senior Associate Scientist
Tumor Angiogenesis Unit

Dr. St. Croix pioneered the development of methods to uncover molecules expressed on the tumor vasculature. He is now exploiting this new knowledge to better understand the process of new blood vessel formation, i.e. angiogenesis, and target the neovasculature that feeds tumors in order to develop more effective therapies for cancer. His recent studies describe the development of new therapeutic monoclonal antibodies that are non-toxic and have potential to aid in the management of cancer and other vascular diseases. The Tumor Angiogenesis Unit develops new approaches to detect and treat primary and metastatic disease through targeting of the tumor microenvironment.

Areas of Expertise
1) tumor angiogenesis 2) endothelial cell biology 3) vascular biology 4) Tumor Endothelial Marker 8 (TEM8)/Anthrax toxin receptor 1 (ANTXR1) 5) TEM5/G-protein coupled receptor 124 (GPR124) 6) Metastasis

Contact Info

Brad St. Croix, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 560, Room 32-34
Frederick, MD 21702-1201
Ph: 301-846-7456
stcroixb@mail.nih.gov

New blood vessel formation, or angiogenesis, is a critical hallmark of solid tumor growth and anti-angiogenic agents have become a vital component of current cancer treatment regimens. The appeal of anti-angiogenic therapy can be attributed to several advantages of targeting the endothelial cells that line blood vessels, rather than the tumor cells themselves. First, endothelial cells are directly exposed to circulating blood, facilitating drug delivery and enabling the use of high molecular weight therapeutics. Second, each vessel capillary supports hundreds of tumor cells. Third, endothelial cells are genetically stable and their ability to develop resistance may be limited. Finally, this type of therapy should be applicable to a wide variety of tumor types. Several anti-angiogenic agents that target the vascular endothelial growth factor (VEGF) pathway have been approved for the treatment of cancer. However, tumors can exploit alternative angiogenesis mechanisms when the VEGF pathway is blocked.

A major current goal of the Tumor Angiogenesis Unit is to understand the mechanisms of VEGF-independent angiogenesis that can lead to persistent tumor angiogenesis and tumor growth. We are also working to understand the biological functions of several cell surface Tumor Endothelial Markers (TEMs) that were previously found to be elevated in the angiogenic vessels of tumors. Two receptors, TEM5/GPR124 and TEM8/ANTXR1 are of particular interest because of their critical role in angiogenesis. We are using several genetically engineered mouse models to understand the functional role of these TEMs in vivo. We are also developing novel therapeutics, such as TEM8 neutralizing antibodies, in order to block angiogenesis and tumor growth. The end goal of this research is to use new molecular information on tumor angiogenesis to develop clinically useful agents for improved diagnostics and therapeutics of cancer and other vascular diseases.

Scientific Focus Areas:
Cancer Biology, Cell Biology

Selected Recent Publications

  1. Szot C, Saha S, Zhang XM, Zhu Z, Hilton MB, Morris K, Seaman S, Dunleavey JM, Hsu KS, Yu GJ, Morris H, Swing DA, Haines DC, Wang Y, Hwang J, Feng Y, Welsch D, DeCrescenzo G, Chaudhary A, Zudaire E, Dimitrov DS, St Croix B.
    J Clin Invest.. Jun 4. pii: 120481. doi: 10.1172/JCI120481. [Epub ahead of print]: 1-17, 2018. [ Journal Article ]
  2. Seaman S, Zhu Z, Saha S, Zhang XM, Yang MY, Hilton MB, Morris K, Szot C, Morris H, Swing DA, Tessarollo L, Smith SW, Degrado S, Borkin D, Jain N, Scheiermann J, Feng Y, Wang Y, Li J, Welsch D, DeCrescenzo G, Chaudhary A, Zudaire E, Klarmann KD, Keller JR, Dimitrov DS, St Croix B
    Cancer Cell. 31(4):501-515.e8. : 2017. [ Journal Article ]
  3. Posokhova E, Shukla A, Seaman S, Volate S, Hilton MB, Wu B, Morris H, Swing DA, Zhou M, Zudaire E, Rubin JS, St Croix B
    Cell Rep. 10(2): 123-130, 2015. [ Journal Article ]
  4. Xu L, Stevens J, Hilton MB, Seaman S, Conrads TP, Veenstra TD, Logsdon D, Morris H, Swing DA, Patel NL, Kalen J, Haines DC, Zudaire E, St Croix B
    Sci Transl Med. 6: 242ra84, 2014. [ Journal Article ]
  5. Yang MY, Hilton MB, Seaman S, Haines DC, Nagashima K, Burks CM, Tessarollo L, Ivanova PT, Brown HA, Umstead TM, Floros J, Chroneos ZC, St Croix B.
    Cell Rep. 3: 1457-64, 2013. [ Journal Article ]

Dr. Brad St. Croix received his Ph.D. in Medical Biophysics from the University of Toronto in 1998, under Dr. Robert S. Kerbel. He trained as a postdoctoral fellow in the laboratory of Dr. Bert Vogelstein at Johns Hopkins University under a fellowship from the National Cancer Institute of Canada. He joined the Mouse Cancer Genetics Program in 2002. His research focuses on the identification of molecules involved in human tumor angiogenesis and utilizes mouse models to translate new molecular information on angiogenesis into the development of novel diagnostics and therapeutics for cancer.

Name Position
James Dunleavey Ph.D. Postdoctoral Fellow (CRTA)
Yang Feng Ph.D. Biologist
Steven Seaman Senior Research Assistant
Kuo-Hui Su Ph.D. Research Fellow

Congratulations to Chris for his 2018 J Clin Invest: paper!

McCann JV, Null JL, & Dudley AC, J Clin InvestDeadly DAaRTS destroy cancer cells via a tumor microenvironment-mediated trigger.

CCR News headlines:  Antibody-linked drug shrinks various types of tumors in preclinical study

 

Congratulations to Steve for his 2017 Cancer Cell paper!

Khan KA & Kerbel RS, Cancer Cell: A CD276 Antibody Guided Missile with One Warhead and Two Targets: The Tumor and Its Vasculature

CCR News headlines: Antibody-linked drug destroys tumor cells and tumor blood vessels in many types of cancer

Cancer Discovery: An Anti-CD276 Antibody–Drug Conjugate Kills Tumor Cells and Vasculature

The Dossier newsletter:  September 2017, Issue 29: The Authors Corner. 

 

Congratulations to Lihong for her 2014 Science Translational Medicine paper!

Cancer Discovery: Dual COX2–VEGF Blockade Suppresses Tumor Angiogenesis and Metastasis

NCI News:  COX-2 – A Novel Target for Reducing Tumor Angiogenesis and Metastasis

CCR connections: Blood Vessel Blockade

Insite: Arthritis Drugs Might Enhance Cancer Chemotherapy

 

Congratulations to Mi Young for her Gpr116 paper that made the May 2013 cover of Cell Reports

 

 

 

Congratulations to Amit for his 2012 Cancer Cell paper!

Bettegowda  C, Science Translational Medicine: Staying Alive: Specifically Targeting Tumor Vessels with Anti-Angiogenesis Therapy

Cain C. Science-Business eXchange:  A TEM to kill

NCI News: TEM8 May Be a Better Anti-Angiogenesis Target

 

Congratulations to Steve for his 2007 Cancer Cell paper!

Li JL, Harris AL, Cancer CellThe potential of new tumor endothelium-specific markers for the development of antivascular therapy.

Robey, R. Nature Reviews Cancer: Angiogenesis: Hidden signatures written in blood.    

CCR Connections:  The Devil Is in the Differences: Highlighting Discrepancies between Tumor and Normal Angiogenesis

NIH News Release: NCI Researchers Discover Genes That Are Turned On at High Levels in Tumor-Associated Blood Vessels of Mice and Humans

Cell Press Science News:  Tumor vessels identified by unique molecular markers

NIH Research Matters: Genes Turned on in Tumor-Associated Blood Vessels