Ashley Lab– In the Department of Medicine

Our Team

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Recent publications from the Ashley Lab

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View our current Cardiomyopathy Seminar Series, held each Tuesday at noon

Principal Investigator: Dr. Euan Ashley

Ziad Ali: Ziad is a fellow in Cardiovascular Medicine at Stanford Hospital and Clinics. After initially training in medicine andsurgery in Cambridge, Ziad joined the Department of Cardiovascular Medicine at the University of Oxford as a Wellcome Trust Clinical Training Fellow. He trained in cardiovascular surgery prior to embarking on a career as a clinician scientist in cardiovascular medicine. He has recently joined the Department of Cardiovascular Medicine at Stanford University. Ziad’s research focuses on the exaggerated biological response to cardiovascular interventions such as venous bypass surgery and percutaneous coronary intervention. His investigative approach utilizes murine models of venous bypass surgery and his own recently developed murine model of balloon angioplasty and stenting. Using these models Ziad has been investigating the role of the endothelium and redox balance in the response to vascular injury and in particular the critical roles of endothelial nitric oxide synthase (eNOS) and angiotensin II (AngII) in these responses. In his spare time, which seems to be spread few and far between, he enjoys spending time with family and friends and shooting hoops.

Selected Publications:

1. Ali ZA, Bursill CA, Douglas GD, McNeill E, Papaspyridinos M, Akhtar AM, Alp NJ, Greaves DR, Channon KM. CCR2-Mediated Anti-inflammatory Effects of Endothelial Tetrahydrobiopterin Inhibit Vascular Injury Induced Accelerated Atherosclerosis. Circulation. 2008;in press.

2. Ali ZA, Callaghan CJ, Nouraei R, Ali AA, Lim E, Dutka DP, Boyle J, Varty K, Gaunt ME. Remote ischemic preconditioning reduces myocardial injury after abdominal aortic aneurysm repair. Circulation. 2007;116:(11)I98-105.

3. Ali ZA, Alp NJ, Lupton H, Arnold N, Greaves DR, Gunn J, Channon KM. Increased In-Stent Stenosis in Apolipoprotein-E Knockout Mice: A Novel Mouse Model of Balloon Angioplasty and Stenting. Arterioscler Thromb Vasc Biol. 2007; 27(4):833-40.

4. Ali ZA, Bursill CB, Choudhury RP, Hu Y, Xu Q, Greaves DR, Channon KM. Adenoviral mediated delivery of a broad spectrum CC-Chemokine Inhibitor reduces vein graft atherosclerosis in apolipoprotein E knockout mice. Circulation. 2005;112:I-235-241.

David Charo

David Charo: David is a Postdoctoral Fellow in Cardiovascular Medicine. He recently completed his Internal Medicine residency here at Stanford as part of the Clinical Investigator Pathway. He majored in molecular biology at Princeton University and received his medical degree at the University of Rochester in chilly New York. He is originally from the bay area and is excited to be back after spending almost a decade in the east coast.

He previously spent a year as a Sarnoff Fellow working in the lab with Dr. Quertermous and Dr. Ashley. His research interests are with the apelin-APJ pathway and how this signaling system works to increase cardiac contractility.

Selected Publications:

1. Charo DN, Ho M, Ernst K, Chen M, Fajardo G, Ho Y, Kawana M, Sheikh AY, Finsterbach T, Bernstein D, Ashley EA, Quertermous T. Apelin is an endogenous regulator of cardiac function. 2008, Submitted.

2. Yue P, Arai T, Terashima M, Sheikh AY, Cao F, Charo DN, Hoyt G, Robbins RC, Ashley EA, Wu JC, Yang PC, Tsao PS. Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse. American Journal of Physiology – Heart and Circulatory Physiology. 2007 May; 292(5):
H2106-18.

3. Tang G, Charo DN, Wang R, Charo IF, Messina L. CCR2 -/- knockout mice revascularize normally in response to severe hindlimb ischemia. Journal of Vascular Surgery. 2004 Oct; 40(4): 786-95.

Frederick Dewey: Rick is a resident in Internal Medicine at Stanford Hospital and Clinics. He hails from Seabrook, Texas by way of Boston, where he studied chemistry and physics at Harvard University prior to medical school at Stanford. His research focuses on the analysis of genetic programs of cardiovascular development and disease. In his former life as an undergraduate, Rick was also a competitive swimmer, but is now content to simply enjoy the athletic feats of others. He enjoys spending time with his wife (a PhD candidate in Biochemistry at Stanford), rowing, hiking, and surfing.

Selected publications:

1. Dewey FE, Rosenthal D, Murphy DJ Jr, Froelicher VF, Ashley EA. Does size matter? Clinical applications of scaling cardiac size and function for body size. Circulation. 2008;117(17):2279-87.

2. Dewey FE, Kapoor JR, Williams RS, Lipinski MJ, Ashley EA, Hadley D, Myers J, Froelicher VF. Ventricular arrhythmias during clinical treadmill testing and prognosis. Arch Intern Med. 2008;168(2):225-34.

3. Leeper NJ, Dewey FE, Ashley EA, Sandri M, Tan SY, Hadley D, Myers J, Froelicher V. Prognostic value of heart rate increase at onset of exercise testing. Circulation. 2007;115(4):468-74.

4. Dewey FE, Freeman JV, Engel G, Oviedo R, Abrol N, Ahmed N, Myers J, Froelicher VF. Novel predictor of prognosis from exercise stress testing: heart rate variability response to the exercise treadmill test. Am Heart J. 2007;153(2):281-8.

Tom Finsterbach: Tom received his PhD from Stanford's Department of Molecular and Cellular Physiology working in the lab of Brian Kobilka. Tom earlier earned an MA from the University of Chicago in the program on the Analysis of Ideas and Study of Methods, an M.Arch from the University of California at Berkeley, and an M.Div from the Jesuit School of Theology at Berkeley's Graduate Theological Union. Tom teaches at Santa Clara University and serves as a Jesuit priest at a Catholic church in Silicon Valley. His current research projects focus on translating other studies into treatments for HCM.

Selected Publications:

1. Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, Deng A, Eichhorn J, Chen MM, Mahajan R, Agrawal R, Greve J, Robbins R, Patterson A, Bernstein D, Quertermous T (2005) The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res 65(1):73-82.

Mikael Mattsson

Mikael Mattsson: Mikael is a PhD-student in Medical Science at Karolinska Institutet, Stockholm, Sweden. He received a Master's degree in physiology from Karolinska Institutet . His research evolves in the area of exercise induced cardiac fatigue and circulatory adaptations. At the Ashley lab he is involved in the projects "extreme physiology" and "the apelin-APJ pathway".

Selected Publications:

1.Mattsson CM, Enqvist JK, Ekblom B. "The Adventure Racing athlete: a physiological profile." Submitted manuscript.

2.Mattsson CM, Enqvist JK, Brink-Elfegoun T, Johansson PH, Bakkman L, Ekblom B. "Reversed drift in heart rate but increased oxygen uptake at fixed work rate during 24 hours ultra-endurance exercise." Scand J Med Sci Sports accepted Oct 5, 2008.

3.Berg U, Enqvist JK, Mattsson CM, Carlsson-Skwirut C, Sundberg CJ, Ekblom B & Bang P. "Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise." Scand J Med Sci Sports 18(6):706-14, 2008.

4.Fernstrom M, Bakkman L, Tonkonogi M, Shabalina IG, Rozhdestvenskaya Z, Mattsson CM, Enqvist JK, Ekblom B & Sahlin K. "Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultra-endurance exercise". J Appl Physiol 102(5):1844-9, 2007.

Aleks
Aleksandra 'Aleks' Pavlovic: Aleks graduated from UC Irvine in 2004, she moved back to the Bay Area in order to get more experience conducting research. Currently she is managing the Stanford Heart Failure Tissue Bank and Database. Also she is working on a variety of heart failure genetics studies including “Dramatic Response to Pharmaceutical Therapy Study” and “Variation in Gene Expression in Patients Taking Ace Inhibitors”. She acts as a genetics liaison in our Hypertrophic Cardiomyopathy Clinic-offering genetic testing and information to patients with this condition. She has a strong interest in the genetics of peripartum cardiomyopathy and is working on a study involving this population.

Selected Publications:

1. Wheeler M, Ho M, Knowles JW, Pavlovic A, Ashley EA (2008).  Pharmacogenetics of Heart Failure: Evidence, Opportunities, and Challenges for Cardiovascular Pharmacogenomics. Journal of Cardiovascular Translational Research 1(2): 25-36.

2. Perez MV, Wheeler M, Ho M, Pavlovic A, Wang P, Ashley EA (2008). Genetics of Arrhythmia: Disease Pathways Beyond Ion Channels. Journal of Cardiovascular Translational Research 1(1): 155-165.

Marco
Marco Perez: Although my formative years training in medicine were spent in chilly New England, the California-raised side of me could not resist returning to the Sunshine State for cardiology fellowship - not to mention world-class mountain biking, skiing and backpacking.  After completion of fellowship, I received an NRSA grant to study the familial aggregation of acquired atrial fibrillation.  Before I begin clinical training in electrophysiology later this year, my lovely fiancé and I will wed in the Andean country of Bolivia. Marco's research projects include pharmacogenomics and networks & arrythmia.

Selected Publications:

1. Perez MV, Wheeler M, Ho M, Pavlovic A, Wang P, Ashley EA. Genetics of Arrhythmia: Disease Pathways Beyond Ion Channels. J Cardiovasc Translational Res. 2008;1(2): 155-165.

Xiumei Qu
Xiumei Qu: Xiumei was born in Shanghai, China. She joined the Ashley Lab in February 2008. Before moving to California, with her husband, she worked in the Division of Organ Transplantation and Immunology at the University of Texas, School of Medicine. She performed various organ transplantation models in rodents and monkeys.

Selected Publications:

1.  Wang M, Qu X, Stepkowski SM, Chou TC, Kahan BD.  Beneficial effect of graft perfusion with anti-T cell receptor monoclonal antibodies on survival of small bowel allografts in rat recipients treated with brequinar alone or in combination with cyclosporine and sirolimus.   Transplantation. 1996 Feb 15;61(3):458-64.

2.  Stepkowski SM, Qu X, Wang ME, Tian L, Chen W, Wancewicz EV, Johnston JF, Bennett CF, Monia BP.   Inhibition of C-raf expression by antisense oligonucleotides extends heart allograft survival in rats.   Transplantation. 2000 Aug 27;70(4):656-61.

3.  Qu X , Kirken RA, Tian L, Wang M, Bennett CF, Stepkowski SM.  Selective inhibition of IL-2 gene expression by IL-2 antisense oligonucleotides blocks heart allograft rejection.   Transplantation. 2001 Sep 15;72(5):915-23.

4.  Zhang Y, Kirken RA, Furian L, Janczewska S, Qu X, Hancock WW, Wang M, Tejpal N, Kerman R, Kahan BD, Stepkowski SM.   Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cells.   J Immunol. 2006 Jan 1;176(1):128-37.

Bob
Bob Turcott: Bob's earliest view of cardiac physiology was from the perspective of an electrical engineer using the tools of signal processing, particularly stochastic point process theory. After completing his doctoral work, he moved from gritty but invigorating pre-Giuliani Manhatten to the pleasantly surreal Stanford environment for medical training. As a student, he developed a consulting relationship with a local ICD company where he incorporated insights from nonlinear dynamical systems theory into computationally unintensive arrhythmia detection algorithms. The fundamental limitations of electrogram-based diagnosis soon motivated his search for a hemodynamic sensor suitable for use in pacemakers and ICDs. He identified an optical approach and developed working prototypes while in medical school, then took a brief hiatus from clinical training to pursue this work full-time. After successfully completing proof of concept studies he returned to Stanford for residency in Internal Medicine. He is presently focusing on hemodynamic assessment and device optimization as a post-doctoral Research Fellow. Long term goals include developing low-cost, noninvasive alternatives to conventional tools of cardiology and facilitating their adoption in underserved areas of the world. A fascinating area of focus of this work is Cuba, which has world-class medical expertise but extremely limited resources. When time allows, he enjoys slipping the surly bonds of earth, though recent weekends have found him battling his nemesis, incisitermes minor.

Selected Publications:

1. Turcott RG and Pavek TJ “Hemodynamic Sensing using Subcutaneous Photoplethysmography,” Am. J. Phys.- Heart Circ. Phys. 2008;295:H2560-72.

Clifton Watt
Clifton Watt: is a post doctoral researcher in the Ashley Lab within Cardiovascular Medicine at Stanford University. He is a Bay Area native who studied computer systems engineering at Stanford University and then rode the Silicon Valley bubble as a software engineer at Sun Microsystems. He then went on to medical school in Chicago at the University of Illinois and completed his residency at the University of Southern California. His research interests include cardiovascular genetics and the application of biomedical informatics principles to cardiovascular research.

Selected Publications:

Matt Wheeler
Matthew Wheeler: is a Postdoctoral Fellow in the Ashley lab and a Clinical Fellow at the Hypertrophic Cardiomyopathy Clinic.  He comes to us from the Stanford Internal Medicine Residency and is a Clinical Investigator Pathway Cardiology Fellow.  He graduated from the University of Chicago with his MD and PhD after undergraduate work at Williams College. He is a native of Potsdam, New York.  Dr. Wheeler previously worked in the laboratory of Dr. Elizabeth McNally at the University of Chicago investigating the mechanisms underlying dilated cardiomyopathy in model systems of muscular dystrophy. His current research includes involvement in several ongoing Ashley lab projects: Pharmacogenetics of Heart Failure, Genetics of Familial Cardiomyopathies, Therapeutics of Hypertrophic Cardiomyopathy, and Preparticipation Screening of Student-Athletes.

Selected Publications:

1. Wheeler MT, Ho M, Knowles, JW, Pavlovic, A, Ashley EA., Pharmacogenetics of Heart Failure: Evidence, Opportunities, and Challenges for Cardiovascular Pharmacogenomics. J Cardiovasc Translational Res. 2008;1(1): 25-36.

2. Ashley EA, Kardos A, Jack ES, Habenbacher W, Wheeler M, Kim YM, Froning J, Myers J, Whyte G, Froelicher V, Douglas P. Angiotensin-converting enzyme genotype predicts cardiac and autonomic responses to prolonged exercise. J Am Coll Cardiol. 2006;48(3):523-31.

3. Wheeler MT, McNally EM. The interaction of coronary tone and cardiac fibrosis. Cur Atherosclerosis Rep. 2005;7(3):219-26.

4. Wheeler MT, Allikian MJ, Heydemann A, Hadhazy M, Zarnegar S, McNally EM. Smooth muscle cell-extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. J Clin Invest. 2004;113(5):668-75.

Alumni

Ayyaz
Ayyaz Ali: is a resident in cardiothoracic surgery at Papworth hospital based in Cambridge, UK.  He is currently undertaking a period of research aimed at evaluating whether non-heart beating donors can be utilized for heart transplantation.  He undertook his undergraduate medical training at the University of Leicester.  Prior to commencing his higher surgical training in cardiothoracic surgery he completed his general surgical training at Addenbrookes hospital, also based in Cambridge.  His research interests include organ donor physiology, clinical outcomes following aortic valve replacement and mechanical circulatory support.

Selected Publications:

1. Ali AA, Thanikachalam M, Lim E, Feccia M, Sudarshan C, Parameshwar J, White P, Large SR. Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation. Eur J Cardiothorac Surg. 2007;31(5):929-33.

2. Ali ZA, Callaghan CJ, Ali AA, Lim E, Munday I, Varty K, Gaunt M. Remote ischemic preconditioning reduces myocardial injury after abdominal aortic aneurysm repair. Circulation. 2007;116(11 Suppl):I98-105.

3. Ali A, Halstead JC, Cafferty F, Sharples L, Rose F, Coulden R, Lee E, Dunning J, Argano V, Tsui S. Are stentless valves superior to modern stented valves? A prospective randomized trial. Circulation. 2006;114(1 Suppl):I535-40.

4. Ali AA, Lim E, Halstead J, Ashrafian H, Ali Z, Khalpey Z, Theodorou P, Chamageorakis T, Kumar P, Jackson C, Pepper J. Porcine or human stentless valves for aortic valve replacement? Results of a 10-year comparative study. J Heart Valve Dis. 2003l;12(4):430-5

Vy-Van Le: I graduated from the School of Medicine at the University of Sherbrooke (Sherbrooke, Province of Quebec, Canada). My Internal Medicine Residency and Cardiology Fellowship  were at the University of Montreal (Montreal, Province of Quebec, Canada). I am a Cardiology Research fellow at the VA Palo Alto and the Stanford Clinics in exercise physiology. I am trying to understand the mechanisms of exercise intolerance in the hypertrophic cardiomyopathy (HCM) population with the use of combined cardiopulmonary testing with stress echocardiography.

Selected Publications:

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