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Jian Cao, M.D.

Professor of Medicine
Leader, Cancer Metastasis and Therapeutics Program, SBU Cancer Center
Email: jian.cao@stonybrookmedicine.edu
Tel: 631-632-1815 (office); 631-632-1816 (lab)

Dr. Cao is a Medical Scientist whose career began shortly after receiving his medical doctoral degree at Zhenzhou University School of Medicine (Henan Medical University), China. His interest in cancer research began during his training in experimental pathology in Peking Union Medical College, Tsinghua University (Chinese Academy of Medical Sciences) in Beijing, China, where he received his Master Degree of Sciences. Dr. Cao’s research background was further strengthened in the field of molecular and cellular biology of cancer during his postdoctoral training in the laboratories of Dr. M. Seiki in Japan and Dr. S. Zucker in New York. He was among the first scientists to discover the membrane type 1-matrix metalloproteinase (MT1-MMP) and demonstrated that this novel protease plays a key role in cancer metastasis. Dr. Cao joined the faculty at Stony Brook University in 1998 as an Assistant Professor, was promoted to Associate Professor in 2008 and then full Professor in 2014. His work at Stony Brook University led to: 1) the demonstration of the role of MT1-MMP in early cancer dissemination; 2) the discovery of an alternative approach targeting specific MMPs; 3) the identification of a novel surrogate marker in cancer cell migration/invasion; and 4) the development of a powerful screening tool for anti-cancer drug discovery using a three-dimensional cell culture system.

The Cao laboratory is interested in the biology and prevention of cancer metastasis. Recognizing that invasiveness is an early critical step for cancer metastasis, the Cao lab has been focused on understanding the mechanism of cancer invasion and on developing novel inhibitors targeting cancer cell invasion. Current projects in the lab fall into three separate but related categories:

1) Projects involving the mechanism of cancer invasion and metastasis:

  • We seek to better understand the role of proteases, especially matrix metalloproteinases (MMPs) in cancer metastasis. We are interested in the roles and mechanisms of MMPs in extracellular matrix degradation, cell migration and epithelial-to-mesenchymal transition;
  • We are interested in charactering the role and mechanism of a novel gene named cell migration inducing protein (CEMIP) that was cloned in the lab in cancer progression;
  • We seek to unravel the mechanism of conversion of stationary cancer stem cells to become invasive ones;
  • We are interested in understanding of the mechanism of hypoxia-induced cancer dissemination.

2) Projects involving anti-cancer drug discovery:   

  • There is an unmet need to improve early cancer diagnosis and prevent/treat metastasis. Regardless of which molecules initiate metastasis, drugs preventing cancer invasion will retard cancer dissemination, hence converting malignant disease into a manageable chronic disease.  We are interesting in identifying small molecular compounds targeting cancer cell invasion using our novel 3D invasion high throughput screening assay; 
  • Mounting evidence has demonstrated that cancer cells require proteases for their invasive behavior.  Theoretically, targeting proteases, e.g. MMPs, interferes with substrate degradation and cell migration, hence, blocking cancer cell invasion. We are chemically modifying the inhibitory peptides and compounds developed in our lab to enhance the potency against cancer cell invasion.

3) Projects involving the development of tools for drug discovery, cancer diagnosis, and prognosis:

  • MT1-MMP is highly expressed in most human invasive cancers. Therefore, utilization of MT1-MMP as a biomarker for identifying cancer cells will provide a better way to distinguish aggressive cancers at an early stage and improve detection of cancer cells more likely to metastasize.  We are working on the development of a specific tumor-homing peptide bound to MT1-MMP at the tumor cell surface for imaging early invasive cancers and for monitoring cancer progression in xenograft tumor models;
  • We are interested in the development of a novel cell-based high throughput screening assay which allows for the simultaneous determination of metastatic cancer cell migratory ability as well as proteolytic activity.

These research areas, resembling the three sides of a triangle, stimulate and challenge the Lab's understanding of cancer pathobiology. The long-term goal of Dr. Cao's lab is to better understand early cancer metastasis and to develop inhibitors to prevent cancer dissemination.

Publications selected since 2010:

  1. Dufour A, Zucker S, Sampson NS, Kuscu C, Cao J. (2010) Role of matrix metalloproteinase-9 (MMP-9) dimers in cell migration: design of inhibitory peptides,  J. Biol. Chem., 12;285(46):35944-56. PMID:20837483.
    *This work was featured in F1000Prime, Post-publication Peer Review, Jan. 2011
  2. Maria Pavlaki, Stanley Zucker, Antoine Dufour, Nikki Calabrese, Wadie Bahou,  and Jian Cao (2010) Furin Functions as a Non Proteolytic Chaperone For Matrix Metalloproteinase-28 (MMP-28): MMP-28 Propeptide Sequence Requirement,  Biochem Res Int. 2011: 2011:630319.
  3. Antoine Dufour, Nicole S. Sampson, Jian Li, Cem Kuscu,  Robert Rizzo, Jennifer L. DeLeon, Jizu Zhi, Nadia Jaber, Eric Liu, Stanley Zucker and Jian Cao (2011) Small Molecule Anti-Cancer Compounds Selectively Target the Hemopexin Domain of Matrix Metalloproteinase-9 (MMP-9), Cancer Res. 71(14):4977-88.
    ӿ This work was featured in SciBX (JUNE 23, 2011 • VOLUME 4 / NUMBER 25), a publishing collaboration between BioCentury Publications, Inc. and Nature Publishing Group.
  4. Kevin Zarrabi, Antoine Dufour, Jian Li, Cem Kuscu, Jizu Zhi, Youjun Hu, Nicole S. Sampson, Stanley Zucker, and Jian Cao (2011) Inhibition of matrix metalloproteinase-14 (MMP-14)-mediated cancer cell migration J. Biol. Chem.  286(38):33167-77.
    ӿ This work was featured in F1000Prime, Post-publication Peer Review, Aug. 2011
  5. Hoang-Lan Nguyen, Stanley Zucker, Pournima Kadam, Cathleen Schmidt, and Jian Cao (2011) MT1-MMP invasive activity promotes prostate cancer aggressiveness via a Wnt5a-mediated increase in ROS, Mol Cancer Res. 9(10):1305-18.
  6. Ding L, Lu Z, Foreman O, Tatum R, Lu Q, Renegar R, Cao J, Chen YH. (2012) Inflammation and Disruption of the Mucosal Architecture in Claudin-7-Deficient Mice. Gastroenterology. Volume 142, Issue 2, Pages 305–315;
  7. Li J, Zucker S, Pulkoski-Gross A, Kuscu C, Karaayvaz M, Ju J, Yao H, Song E, Cao J. (2012) ӿ Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking.  PLoS One 7(6):e38403;
    ӿ This work was featured in Faculty of 1000, Post-publication Peer Review, June 2012
  8. Cem Kuscu, Nikki Evensen, Deborah Kim, You-Jun Hu, Stanley Zucker, and Jian Cao (2012) Transcriptional and Epigenetic Regulation of KIAA1199 Gene Expression In Human Breast Cancer. PLoS One 2012;7(9):e44661.
    ӿThis work was featured in World Biomedical Frontiers, Aug., 2013
  9. Nikki A Evensen, Cem Kuscu, Kevin Zarrabi, Antoine Dufour, Pournima Kadam, You-jun Hu, Ashleigh Pulkoski-Gross, Hoang-Lan Nguyen, Wadie F. Bahou, Stanley Zucker, and Jian Cao (2013) Unraveling the Role of KIAA1199, A Novel Endoplasmic Reticulum Protein in Cancer Cell Migration,  J Natl Cancer Inst. 105(18):1402-16.
  10. Vasko R, Xavier S, Chen J, Lin CH, Ratliff B, Rabadi M, Maizel J, Tanokuchi R, Zhang F, Cao J, Goligorsky MS.  Endothelial Sirtuin 1 Deficiency Perpetrates Nephrosclerosis through Downregulation of Matrix Metalloproteinase-14: Relevance to Fibrosis of Vascular Senescence. J J Am Soc Nephrol. 2014 Feb;25(2):276-91
  11. Nikki A Evensen, Jian Li, Jie Yang, Nicole S. Sampson, Stanley Zucker, and Jian Cao (2013): Development of A Novel Three-dimensional High-throughput Invasion Assay for Anti-cancer Drug Discovery.  PLoS One 2013  Dec 11;8(12):e82811.
  12. Pulkoski-Gross AE, Li J, Zheng C, Li Y, Ouyang N, Rigas B, Zucker S, Cao J. Repurposing the Anti-psychotic Trifluoperazine as an Anti-metastasis Agent. Mol Pharmacol. 2014 Dec 31. [Epub ahead of print].