Kenneth Walsh, Ph.D.

Professor of Medicine

Education:

Ph.D. – University of California, Berkeley

General field of research:

Cardiovascular Biology

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research
Whitaker Cardiovascular Institute

Contact information:

Office
700 Albany Street, W611
Phone: (617) 414-2390

Lab
700 Albany Street, W619
Phone: (617) 414-2395
Fax: (617) 414-2391

kxwalsh@bu.edu

Other research websites:

http://www.kwalshlab.org

Research group information:

David Chess, PhD	chessdj@bu.edu
Jennifer Duffen (graduate student)	jparker@bu.edu
José J. Fuster Ortuño, PhD	jjfuster@bu.edu
Ryosuke Kikuchi, PhD	kryosuke@bu.edu
Sonomi Maruyama, MD, PhD	maruson@bu.edu
Gladys Ngoh, PhD	gnafor01@bu.edu
Matthew Phillippo (tech)	mattphil@bu.edu
Taina A. Rokotuiveikau (tech)	tainar@bu.edu
Ippei Shimizu, MD, PhD.	ippei@bu.edu
Kenneth Walsh, PhD, Professor	kxwalsh@bu.edu
Linda Whittaker (admin)	ldwhitt@bu.edu
Marian Zuriaga Herrero, PhD	marianzh@bu.edu

Keywords:

Cardiovascular; Cell Cycle; Glucose Metabolism; Obesity; Myokine

Summary of research interest:

Research in the Walsh laboratory is focused in a number of related areas. A major project investigates the signaling- and transcriptional-regulatory mechanisms that control both normal and pathological tissue growth in the cardiovascular system. Many of these studies involve analyses of the PI3-kinase/Akt/GSK/Forkhead signaling axis. This pathway is of critical importance in the regulation of organ growth and body size. Signaling through this pathway controls cellular enlargement (hypertrophy), cell death (apoptosis), and blood vessel recruitment and growth (angiogenesis). We have shown that the PI3-kinase/Akt/GSK/Forkhead signaling axis regulates multiple steps critical in angiogenesis including endothelial cell apoptosis, differentiation, nitric oxide production and migration. We have also shown that some of these signaling steps are important for cardiac hypertrophy during normal postnatal development, and that they regulate myocyte survival in models of heart disease. Using mouse genetic models that alter the expression of Akt in cardiac cells, we have found that perturbations in crosstalk mechanisms between cardiac myocytes and vascular endothelial cells contribute to the transitions from compensated hypertrophy to heart failure. Factors involved in this regulation include VEGF, Fstl1, Fstl3 and Activin-A. Subsequent studies in patient populations have shown that at least one of these factors (Fstl1) is upregulated in clinical heart failure and is predictive of mortality in patients with acute coronary syndrome.

Related studies examine how alterations in the expression of adipocyte-derived cytokines, referred to as adipokines, interfere with normal signaling within the cardiovascular system and thereby contribute to cardiovascular disease. Adiponectin is an anti-inflammatory adipokine that is down-regulated in obesity. Studies by the Walsh laboratory were first to show that adiponectin directly acts on the heart and vasculature as a cardio-protective factor. Recently this laboratory identified Sfrp5 as a new anti-inflammatory adipokine, and demonstrated that it functions to control systemic metabolism through regulation of non-canonical Wnt signaling in adipose tissue. Finally, we are examining how age-associated loss of skeletal muscle mass affects metabolic and cardiovascular function, and is exploring the possibility that muscle-secreted factors (myokines) confer some of the benefits of exercise training on cardiovascular and metabolic diseases.

Recent publications:

K. N. Papanicolaou, R. Kikuchi, G. A. Ngoh, K. A. Coughlan, I. Dominguez, W. C. Stanley, K. Walsh (2012). Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart. Circ. Res. [Epub ahead of print Aug 17].

K.N. Papanicolaou, R.J. Khairallah, G.A. Ngoh, A. Chikando, I. Luptak, K.M. O’Shea, D.D. Riley, J.J. Lugus, W.S. Colucci, W.J. Lederer, W.C. Stanley,
K. Walsh (2011)..Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol. Cell. Biol. 31:1309-1328.

M. Shimano, N. Ouchi, K. Nakamura, Y. Oshima, A. Higuchi, D.R. Pimentel, K.D. Panse, E. Lara-Pezzi, S.J. Lee, F. Sam, K. Walsh (2011). Cardiac myocyte-specific ablation of Follistatin-like 3 attenuates stress-induced myocardial hypertrophy. J. Biol. Chem.
286:9840-9848. Editor’s Choice feature in Science Signaling.

N. Ouchi, A. Higuchi, K. Ohashi, Y. Oshima, N. Gokce, R. Shibata, Y. Akasaki, A. Shimono, K. Walsh (2010). Sfrp5 Is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science.
329:454-457. Accompanied by editorial.

K. N. Papanicolaou, R. Kikuchi, G. A. Ngoh, K. A. Coughlan, I. Dominguez, W. C. Stanley, K. Walsh (2012). Mitofusins 1 and 2
are essential for postnatal metabolic remodeling in heart. Circ. Res. [Epub ahead of print Aug 17].

M. Shimano, N. Ouchi, K. Nakamura, Y. Oshima, A. Higuchi, D.R. Pimentel, K.D. Panse, E. Lara-Pezzi, S.J. Lee, F. Sam, K. Walsh (2011). Cardiac myocyte-specific
ablation of Follistatin-like 3 attenuates stress-induced myocardial hypertrophy. J. Biol. Chem.
286:9840-9848. Editor’s Choice feature in Science Signaling.

Shibata R., K. Sato, D.R. Pimental, Y. Takemura, S. Kihara, K. Ohashi, T. Funahashi, N. Ouchi, K. Walsh. 2005. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2- dependent mechanisms. Nature Med. 10:1096-1103.

Shiojima I., K. Sato, Y. Izumiya, S. Schiekofer, M. Ito, R. Liao, W.S. Colucci, K. Walsh. 2005. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J. Clin. Invest. 115:2108-2118.

Shibata R., N. Ouchi, M. Ito, S. Kihara, I. Shiojima, D.R. Pimentel, M. Kumada, K. Sato, S. Schiekofer, K. Ohashi, T. Funahashi, W.S. Colucci, K. Walsh. 2004. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nature Med. 10:1384-1389.