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Radu V. Stan, M.D., Ph.D.

Title(s):
Associate Professor of Pathology
Associate Professor of Microbiology and Immunology
Director, Optical Cell Imaging Facility, Co-Director, Irradiation, Pre-clinical Imaging and Microscopy Shared Resource, Norris Cotton Cancer Center, Lebanon, NH

Department(s):
Pathology
Microbiology and Immunology

Education:
M.D. 1993 - Cluj, Romania
Postdoctoral, 1994-1999 at University of California San Diego Medical (Advisor George E. Palade)
Ph.D. 2013 - Groningen, The Netherlands

Programs:
Heart and Vascular Research Center
Norris Cotton Cancer Center
Program in Experimental and Molecular Medicine

NIH Biosketch:
Stan_R_BIO_2010-12-09.pdf

Websites:
http://www.dartmouth.edu/~radustan/
http://www.dartmouth.edu/~hvrc/

Contact Information:

Geisel School of Medicine at Dartmouth
Department of Pathology
One Medical Center Drive
Lebanon NH 03756

Office: Borwell 502W
Phone: 603-650-8781
Fax: 603-650-6166
Email: Radu.V.Stan@Dartmouth.edu


Professional Interests:

Our laboratory studies the biology of endothelial cells related to cardiovascular function in normal undisturbed tissues as well as in adaptive and pathologic processes underlying inflammatory diseases and cancer.

Our efforts are currently focused on several distinct but interactive project areas, relying on a wide array of experimental approaches including electron microscopy, fluorescence live cell imaging, biochemical, cell biological, genetic and whole animal physiology approaches. These current focus areas are:

1) Cell biology of the endothelium: The laboratory studies how, on one hand, fundamental mechanisms of signaling and membrane traffic control endothelial cell differentiation and organization in different vascular beds. Specific endothelial structures (fenestrae, transendothelial channels, vesiculo-vacuolar organelles, caveolae and other vesicular carriers) have been shown to mediate the exchanges between blood and tissues. Our laboratory has cloned and characterized Plasmalemma Vesicle Associated Protein (PLVAP) gene, whose gene product, the PLVAP/PV1 protein, is the first known component of the endothelial stomatal and fenestral diaphragms, present on the endothelial structures involved in permeability. Taking advantage of PV1 we are currently trying to understand the biogenesis, cellular function and regulation of the endothelial structures involved in transendothelial exchange.

2) Pathways of exchange between blood and the interstitial space: We are particularly interested in elucidating the molecular mechanisms involved in the transendothelial exchanges between the blood plasma and the interstitial fluid in health and disease. We are using genetically engineered mice generated in the lab to understand the precise role of vesicular trafficking as well as the role of endothelial microdomains such as transendothelial channels, fenestrae and vesiculo-vacuolar organelles in microvascular permeability.

3) Role of PV1 in inflammation: PV1 is unregulated on the activated endothelium in inflammatory lesions. Downregulation of PV1 results in blunted diapedesis of leukocytes, which prompted studies as to the precise mechanism by which PV1 participates in this process.

4) Role of PV1 in cancer: Previous work has shown that PV1 is expressed in most, if not all, solid tumor vessels. We have shown that intratumoral deletion of PV1 results in impaired tumor growth, which prompted studies as to the precise mechanism by which PV1 promotes tumor formation and growth.



Keywords: Inflammation, cancer, angiogenesis, microvascular permeability endothelial differentiation, endothelial cell biology, endocytosis, transcytosis, fenestrae, caveolae, transendothelial channels.

Rotations and Thesis Projects:

1. Determine the role of PV1 in inflammation.
2. Determine the role of PV1 protein in cancer. We are employing multiple cancer models to study the role of PV1 in tumor growth.
3. Development of anticancer diagnostics and therapeutics.
4. Characterize the role of PV1 and its interacting partners in the biogenesis and function of caveolae and fenestrae. Determine the roles of these endothelial structures in vivo.

Grant Information:

S10D010330
R21CA172983
R21CA175592

Courses Taught:

General Pathology DMS I
PEMM 101
PEMM 102
PEMM 275
PEMM 126
MICRO144

Biography:

Dr. Stan did his postdoctoral training 1994-1999 at University of California San Diego Medical in the laboratory of George Palade, where he worked on the role of caveolae/lipid rafts and fenestrae in the cell biology of vascular permeability. He joined the faculty at UCSD as a Project Scientist (1999 ) and Research Assistant Professor (2000) in the Department of Cellular and Molecular Medicine continuing his studies of the molecular mechanisms of vascular permeability and the structures involved. In 2004, Dr. Stan joined the faculty of the departments of Pathology, and of Microbiology and Immunology at Dartmouth Medical School as an Assistant Professor and became Associate Professor in 2009. Currently, he is a member of the Heart and Vascular Research Center, Norris Cotton Cancer Center and affiliated with the Immunology COBRE. Since 2013 Dr Stan serves as the Director of the Optical Cell Imaging Facility and Co-Director, Irradiation, Pre-clinical Imaging and Microscopy Shared Resource, Norris Cotton Cancer Center.


Selected Publications:

 

Tichauer KM, Deharvengt SJ, Samkoe KS, Gunn JR, Bosenberg MW, Turk MJ, Hasan T, Stan RV, Pogue BW
Tumor endothelial marker imaging in melanomas using dual-tracer fluorescence molecular imaging.
Mol Imaging Biol 2014 Jun; 16(3):372-82
PMID: 24217944

Busch AM, Johnson KC, Stan RV, Sanglikar A, Ahmed Y, Dmitrovsky E, Freemantle SJ
Evidence for tankyrases as antineoplastic targets in lung cancer.
BMC Cancer 2013 Apr 28; 13:211
PMID: 23621985

Hoopes PJ, Petryk AA, Tate JA, Savellano MS, Strawbridge RR, Giustini AJ, Stan RV, Gimi B, Garwood M
Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy.
Proc SPIE 2013 Feb 26; 8584
PMID: 25285190

Stan RV, Tse D, Deharvengt SJ, Smits NC, Xu Y, Luciano MR, McGarry CL, Buitendijk M, Nemani KV, Elgueta R, Kobayashi T, Shipman SL, Moodie KL, Daghlian CP, Ernst PA, Lee HK, Suriawinata AA, Schned AR, Longnecker DS, Fiering SN, Noelle RJ, Gimi B, Shworak NW, Carriere C
The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.
Dev Cell 2012 Dec 11; 23(6):1203-18
PMID: 23237953

Wasiuk A, Dalton DK, Schpero WL, Stan RV, Conejo-Garcia JR, Noelle RJ
Mast cells impair the development of protective anti-tumor immunity.
Cancer Immunol Immunother 2012 Dec; 61(12):2273-82
PMID: 22684520

Deharvengt SJ, Tse D, Sideleva O, McGarry C, Gunn JR, Longnecker DS, Carriere C, Stan RV
PV1 down-regulation via shRNA inhibits the growth of pancreatic adenocarcinoma xenografts.
J Cell Mol Med 2012 Nov; 16(11):2690-700
PMID: 22568538

Simone EA, Zern BJ, Chacko AM, Mikitsh JL, Blankemeyer ER, Muro S, Stan RV, Muzykantov VR
Endothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124.
Biomaterials 2012 Jul; 33(21):5406-13
PMID: 22560201

Tkachenko E, Tse D, Sideleva O, Deharvengt SJ, Luciano MR, Xu Y, McGarry CL, Chidlow J, Pilch PF, Sessa WC, Toomre DK, Stan RV
Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells.
PLoS One 2012; 7(3):e32655
PMID: 22403691

Tse D, Armstrong DA, Oppenheim A, Kuksin D, Norkin L, Stan RV
Plasmalemmal vesicle associated protein (PV1) modulates SV40 virus infectivity in CV-1 cells.
Biochem Biophys Res Commun 2011 Aug 26; 412(2):220-5
PMID: 21827737

Engel D, Beckers L, Wijnands E, Seijkens T, Lievens D, Drechsler M, Gerdes N, Soehnlein O, Daemen MJ, Stan RV, Biessen EA, Lutgens E
Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response.
FASEB J 2011 Nov; 25(11):3838-48
PMID: 21795505