Dalman Research Lab

Research

Our research focuses on abdominal aortic aneurysm (AAA), a life-threatening inflammatory vascular disease affecting one million of Americans. We use two rodent models of human AAA disease, the transient intra-aortic infusion of porcine pancreatic elastase in C57BL/6 mice (the PPE model) and the angiotensin II infusion in hypercholesterolimic apolipoprotein E-deficient mice (the Ang II/ApoE KO model), to study the mechanic, cellular and molecular events that are involved in the initiation and progression of AAA at its fundamental levels. Our current efforts are to define the pathophysiological roles of macrophages and angiogenesis, the two key pathological features of human AAA, in the development of AAA disease using genetically modified materials/mice and pharmacological intervention. To provide the experimental data for initiating new clinical trial for pharmacological treatment of AAA, we also conduct preclinical studies to evaluate the therapeutic potentials of existing anti-inflammatory drugs and novel compounds in preventing or limiting the progression of AAA disease in the two AAA models.

Current funded research projects

  1. AAA disease: Mechanism, stratification and treatment (NIH, project number 5P50HL083800-05, 2006.5.1-2012-4.30)

  2. Mechanisms in innovation in vascular medicine (NIH, project number 5T32HL098049-02, 2010.7.1-2015.6.30)

  3. Critical role of inflammatory macrophages in AAA pathogenesis (NIH, project number 1R21HL109750-01, 2011.8.8-2013.5.31)

  4. Mechanisms and significance of angiogenesis in AAA pathogenesis (NIH, project number 1R21HL112122-01, 2012.1.1-2013.12.31)

Research Group

Principal Investigator

Ronald Lee. Dalman, MD
Professor of Surgery & Chief, Division of Vascular Surgery
Stanford University School of Medicine

Current members

Naoki Fujimura, MD/PhD (Visiting scholar, Keio University School of Medicine, Japan)
Keith Glover, BS (Medical student, Stanford University School of Medicine)
Alicia Hamar (Undergraduate Student, Stanford University)
Xiaolei Hu, MD (Visiting scholar, Central South University School of Medicine, China)
Malika Kumar (Undergraduate student, Stanford University)
Hiroki Tanaka, MD/PhD (Visiting scholar, Hamamatsu Medical University, Japan)
Wei Wang, MD/PhD (Central South University School of Medicine, China)
Baohui Xu, MD/PhD (Senior research scientist, Stanford University School of Medicine)
Haojun Xuan, MD (Research associate, Stanford University School of Medicine)

Former members

Thomas A. Abbruzzese (General and Vascular Surgery Specialists Inc, Boynton Beach, Florida)
Monica M. Dua, MD (Stanford University School of Medicine, Stanford, California)
Katsuyuki Hoshina, MD/PhD (University of Tokyo, Tokyo, Japan)
Yasunori Iida, MD/PhD (Tokyo Medical University, Tokyo, Japan)
John K. Karwowski MD (Weill Cornell Medical College, New York)
Kim Kortekaas (Leiden University Medical Center, Leiden, The Netherlands)
Noriyuki Miyama, MD/PhD (Tokyo Medical University, Tokyo, Japan)
Takeshi K. Nakahashi
Geoffrey M. Schultz, MD (Stanford University School of Medicine, Stanford, California)
Eiketsu Sho, MD/PhD (Kunming Biomed International, China)
Mien Sho, MD/PhD (Shanghai ChemPartner Co., Ltd, Shanghai, China)
Maureen M. Tedesco, MD (Stanford University School of Medicine, Stanford, California)

Representative publications in AAA disease(for full publications, search PubMed by Dalman RL)

  1. Kitagawa T, Kosuge H, Uchida M, Iida Y, Dalman RL, Douglas T, McConnell MV. RGD targeting of human ferritin iron-oxide nanoparticles enhances in vivo molecular MRI of experimental aortic aneurysms. J Cardiovasc Magn Reson. 2012;14 (Suppl 1):M9.
  2. Maegdefessel L, Azuma J, Toh R, Deng A, Merk DR, Raiesdana A, Leeper NJ, Raaz  U, Schoelmerich AM, McConnell MV, Dalman RL, Spin JM, Tsao PS. MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion. Sci Transl Med. 2012; 4:122.
  3. Maegdefessel L, Azuma J, Toh R, Merk DR, Deng A, Chin JT, Raaz U, Schoelmerich AM, Raiesdana A, Leeper NJ, McConnell MV, Dalman RL, Spin JM, Tsao PS. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J Clin Invest. 2012; 122:497-506.
  4. Miyama N, Dua MM, Schultz GM, Kosuge H, Terashima M, Pisani LJ, Dalman RL, McConnell MV. Bioluminescence and Magnetic Resonance Imaging of Macrophage Homing to Experimental Abdominal Aortic Aneurysms. Mol Imaging. 2011 Jan 11. [Epub ahead of print].
  5. Spin JM, Hsu M, Azuma J, Tedesco MM, Deng A, Dyer JS, Maegdefessel L, Dalman RL, Tsao PS. Transcriptional profiling and network analysis of the murine angiotensin II-induced abdominal aortic aneurysm. Physiol Genomics. 2011; 43:993-1003.
  6. Kitagawa T, Kosuge H, Uchida M, Dua MM, Iida Y, Dalman RL, Douglas T, McConnell MV. RGD-Conjugated Human Ferritin Nanoparticles for Imaging Vascular Inflammation and Angiogenesis in Experimental Carotid and Aortic Disease. Mol Imaging Biol. 2011 Jun 3. [Epub ahead of print].
  7. Suh GY, Les AS, Tenforde AS, Shadden SC, Spilker RL, Yeung JJ, Cheng CP, Herfkens RJ, Dalman RL, Taylor CA. Hemodynamic changes quantified in abdominal aortic aneurysms with increasing exercise intensity using mr exercise imaging and image-based computational fluid dynamics. Ann Biomed Eng. 2011; 39:2186-202.
  8. Myers J, Powell A, Smith K, Fonda H, Dalman RL; Stanford AAA SCCOR Investigators. Cardiopulmonary exercise testing in small abdominal aortic aneurysm: profile, safety, and mortality estimates. Eur J Cardiovasc Prev Rehabil. 2011;18:459-66.
  9. Goergen CJ, Azuma J, Barr KN, Magdefessel L, Kallop DY, Gogineni A, GrewallA, Weimer RM, Connolly AJ, Dalman RL, Taylor CA, Tsao PS, Greve JM. Influences of aortic motion and curvature on vessel expansion in murine experimental aneurysms. Arterioscler Thromb Vasc Biol. 2011;31:270-9.
  10. Myers JN, White JJ, Narasimhan B, Dalman RL. Effects of exercise training in patients with abdominal aortic aneurysm: preliminary results from a randomized trial. J Cardiopulm Rehabil Prev. 2010;30:374-83.
  11. Miyama N, Dua MM, Yeung JJ, Schultz GM, Asagami T, Sho E, Sho M, Dalman RL. Hyperglycemia limits experimental aortic aneurysm progression. J Vasc Surg. 2010;52:975-83.
  12. Dua MM, Miyama N, Azuma J, Schultz GM, Sho M, Morser J, Dalman RL. Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease. Surgery. 2010;148:429-35.
  13. Schultz G, Tedesco MM, Sho E, Nishimura T, Sharif S, Du X, Myles T, Morser J, Dalman RL, Leung LL. Enhanced abdominal aortic aneurysm formation in thrombin-activatable procarboxypeptidase B-deficient mice. Arterioscler Thromb Vasc Biol. 2010;30:1363-70.
  14. Dua MM, Dalman RL. Hemodynamic influences on abdominal aortic aneurysm disease: Application of biomechanics to aneurysm pathophysiology. Vascul Pharmacol. 2010;53:11-21.
  15. Les AS, Shadden SC, Figueroa CA, Park JM, Tedesco MM, Herfkens RJ, Dalman RL, Taylor CA. Quantification of hemodynamics in abdominal aortic aneurysms during rest and exercise using magnetic resonance imaging and computational fluid dynamics. Ann Biomed Eng. 2010; 38:1288-313.
  16. Tenforde AS, Cheng CP, Suh GY, Herfkens RJ, Dalman RL, Taylor CA. Quantifying in vivo hemodynamic response to exercise in patients with intermittent claudication and abdominal aortic aneurysms using cine phase-contrast MRI. J Magn Reson Imaging. 2010;31:425-9.
  17. Tedesco MM, Terashima M, Blankenberg FG, Levashova Z, Spin JM, Backer MV, Backer JM, Sho M, Sho E, McConnell MV, Dalman RL. Analysis of in situ and ex vivo vascular endothelial growth factor receptor expression during experimental aortic aneurysm progression. Arterioscler Thromb Vasc Biol. 2009;29:1452-7.
  18. Leeper NJ, Tedesco MM, Kojima Y, Schultz GM, Kundu RK, Ashley EA, Tsao PS, Dalman RL, Quertermous T. Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation. Am J Physiol Heart Circ Physiol. 2009;29:H1329-35.
  19. Golledge J, Tsao PS, Dalman RL, Norman PE. Circulating markers of abdominal aortic aneurysm presence and progression. Circulation. 2008;118:2382-92.
  20. Baxter BT, Terrin MC, Dalman RL. Medical management of small abdominal aortic aneurysms. Circulation. 2008;117:1883-9.
  21. White JJ, Dalman RL. Gaining new insights into early abdominal aortic aneurysm disease. Perm J. 2008;12:10-4.
  22. Dalman RL, Tedesco MM, Myers J, Taylor CA. AAA disease: mechanism, stratification, and treatment. Ann N Y Acad Sci. 2006;1085:92-109.
  23. Tedesco MM, Dalman RL. Flow-mediated effects on abdominal aortic aneurysms. Future Cardiol. 2006;2:477-82.
  24. Sho E, Sho M, Nanjo H, Kawamura K, Masuda H, Dalman RL. Comparison of cell-type-specific vs transmural aortic gene expression in experimental aneurysms. J Vasc Surg. 2005;41:844-52.
  25. Hoshina K, Koyama H, Miyata T, Shigematsu H, Takato T, Dalman RL, Nagawa H. Aortic wall cell proliferation via basic fibroblast growth factor gene transfer limits progression of experimental abdominal aortic aneurysm. J Vasc Surg. 2004;40:512-8.
  26. Sho E, Sho M, Nanjo H, Kawamura K, Masuda H, Dalman RL. Hemodynamic regulation of CD34+ cell localization and differentiation in experimental aneurysms. Arterioscler Thromb Vasc Biol. 2004;24:1916-21.
  27. Sho E, Chu J, Sho M, Fernandes B, Judd D, Ganesan P, Kimura H, Dalman RL. Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms. J Vasc Surg. 2004;39:1312-21.
  28. Sho E, Sho M, Hoshina K, Kimura H, Nakahashi TK, Dalman RL. Hemodynamic forces regulate mural macrophage infiltration in experimental aortic aneurysms. Exp Mol Pathol. 2004;76:108-16.
  29. Dalman RL. Oxidative stress and abdominal aneurysms: how aortic hemodynamic conditions may influence AAA disease. Cardiovasc Surg. 2003;11:417-9.
  30. Hoshina K, Sho E, Sho M, Nakahashi TK, Dalman RL. Wall shear stress and strain modulate experimental aneurysm cellularity. J Vasc Surg. 2003;37:1067-74.
  31. Nakahashi TK, Hoshina K, Tsao PS, Sho E, Sho M, Karwowski JK, Yeh C, Yang RB, Topper JN, Dalman RL. Flow loading induces macrophage antioxidative gene expression in experimental aneurysms. Arterioscler Thromb Vasc Biol. 2002;22:2017-22.
  32. Karwowski JK, Markezich A, Whitson J, Abbruzzese TA, Zarins CK, Dalman RL. Dose-dependent limitation of arterial enlargement by the matrix metalloproteinase inhibitor RS-113,456. J Surg Res. 1999;87:122-9.

 

Contact us

Research opportunity

Dr. Ronald L. Dalman, MD ( rld@stanford.edu)

Laboratory address

Room P323, MSLS building
1201 Welch road, Stanford, CA94305-5102
(Phone) 650-724-7582