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Summer Lab

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Ross Summer, MD

The Summer lab is a basic science/translational medicine laboratory in the Center of Translational Medicine at Thomas Jefferson University whose overarching goal is to develop novel treatments for patients with various lung diseases including Acute Respiratory Distress Syndrome and Pulmonary Fibrosis.

An overview of active projects is summarized below. Dr. Summer’s group invites those interested in more detailed views of our work to review some of our most recent publications (see below).  

Areas of Investigation:

Project 1: Elucidate the mechanisms by which obesity promotes the development of ARDS.

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that has no effective treatment and causes death in approximately 1/3 of all patients.  Obesity is now recognized as an important predisposing factor for the development of ARDS but the mechanisms mediating this association are unknown.  Dr. Summer's laboratory employs genetic and diet-induced obesity models to further elucidate the mechanisms by which obesity promotes the development of ARDS. The primary objective of these studies is to identify unique biological pathways that can be exploited for developing treatments for patients with ARDS.

Project 2: Elucidate the mechanisms by which chronic alcohol exposure promotes the development of inflammatory lung diseases.

Chronic alcohol abuse is a major public health problem and leads to increased morbidity and mortality. Alcohol’s injurious effects are observed in all tissues, but certain organs, such the liver, brain and lung appear to be particularly susceptible to its ill effects. In the lung, heavy alcohol intake promotes the onset, and enhances the severity of various inflammatory lung conditions such as bacterial pneumonia and ARDS.   In recent work, Dr. Summer’s laboratory has discovered a novel mechanism by which chronic alcohol ingestion induces functional impairments in the lung’s immune system. His group showed that chronic alcohol induces a wide range of metabolic changes that act together to promote triglyceride and fatty acid accumulation in the lung. Further, they show that lipid accumulation mediates many of the suppressive effects of alcohol on immune cell function in the lung.  Collectively, these observations have led his group to begin testing whether lipid lowering therapies might be effective for treating various alcohol-related inflammatory lung disorders.

Project 3: Determine whether metabolic disturbances in the lung epithelium contribute to the pathogenesis of pulmonary fibrosis.  

Pulmonary fibrosis refers to a group of conditions that cause scarring of the lung. These conditions have limited treatments, and those that are available are only marginally effective. It is now generally accepted that injury to the lung’s epithelium plays a causal role in the pathogenesis of pulmonary fibrosis but the mechanisms by which epithelial injury drives fibrotic responses remain unknown. Recent work in Dr. Summer’s laboratory indicates that metabolic disturbances in the lung epithelium play a key pathogenic role in promoting fibrotic responses. These findings have led his laboratory to begin testing whether reversing these metabolic derangements might limit the onset or progression of lung fibrosis in mice.

Recent Publicarions

http://www.ncbi.nlm.nih.gov/pubmed/?term=summer+r

1.     Romero F., Shah D., Duong M, Penn RB., Fessler MB., Madenspacher J., Stafstrom W., Kavuru M., Lu B., Kallen C.B., Walsh K,. and Summer R. A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis. Am J Resp Cell Mol Biol 2014 Dec [25409201]  http://www.ncbi.nlm.nih.gov/pubmed/25409201

2.     Walkey AJ, Demissie S, Shah D, Romero F, Puklin L, Summer RS. Plasma Adiponectin, Clinical Factors, and Patient Outcomes during the Acute Respiratory Distress Syndrome. PLoS One. 2014 Sep [PMID 25259893]  http://www.ncbi.nlm.nih.gov/pubmed/25259893

3.      Romero F., Shah D., Duong M, Stafstrom W., Hoek J.B., Kallen C.B., Lang C.H. and Summer R. (2014) Chronic alcohol ingestion in rats alters lung metabolism, promotes lipid accumulation, and impairs alveolar macrophage functions. Am J Resp Cell Mol Biol 2014 June 18. [E-pub ahead of print]. [PMID 24940828]  http://www.ncbi.nlm.nih.gov/pubmed/24940828

4.      Ding, SY, Lee, MY., Summer, R., Liu, L., Fried, S.K., Pilch, PF. Paul F. Pilch Pleiotropic Effects of Cavin-1 Deficiency on Lipid Metabolism J. Biol. Chem. PMID: [24509860]

5.      Shah, D., Romero, F., Stafstrom, W., Duong, M., Summer, R. Extracellular ATP mediates the late phase of neutrophil recruitment to the lung after LPS induced injury. 2014 Jan;306(2):L152-61 [PMID: 24285266].  http://www.ncbi.nlm.nih.gov/pubmed/24285266

6.      Govender, P., Romero, F., Shah, D., Paez, J., Ding, SY., Liu, L., Gower, A., Baez, E., Aly, S.S., Pilch, P., Summer, R. Cavin1; a regulator of lung function and macrophage phenotype, PlosOne 2013. [PMID: 23634221]. http://www.ncbi.nlm.nih.gov/pubmed/23634221

7.      Fang F, Liu L, Yang Y, Tamaki Z, Wei J, Marangoni RG, Bhattacharyya S, Summer RS, Ye B, Varga J. The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy. Arthritis Res Ther. 2012 Oct 23;14(5):R229 [PMID:23092446].

8.      Konter, J., Li, S., Parker, J., Ouchi, N., Fine, A., Walsh, K., Summer, R. Adiponectin attenuates LPS-induced acute lung injury in mice. J Immunol. 2012 Jan 15;188(2):854-63. [PMID: 22156343].

9.      Walkey, A., Rice, T., Konter, J., Ouchi, N., Shibata, R., Walsh, K., deBoisblanc, B., Summer, R. Plasma Adiponectin and Clinical Outcomes in Critically Ill Subjects with Respiratory Failure. Critical Care Medicine 2010 Dec;38(12):2415-6. [PMID: 20890191].

10.  Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, Amstrup Pedersen A, Kalthoff C, Tullin S, Sams A, Summer R, Walsh K. Adiponectin promotes macrophage polarization towards an anti-inflammatory phenotype.  J Biol Chem. 2009 Dec 22. [PMID: 20028977].

11.  Summer, R., Fiack CA, Ikeda Y, Sato K, Dwyer D, Ouchi N, Fine A, Farber HW, Walsh K. Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease, Am J Physiol Lung Cell Mol Physiol. Sep;297(3):L432-8. 2009. [PMID: 19561137].

12.  Summer, R., Little, F, Ouchi, N, Takemura,Y, Aprahamian, T., Dwyer, D, Fitzsimmons, K., Suki, B., Parameswaran, H., Fine, A., Walsh, K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin deficient mice. Am J Physiol Lung Cell Mol Physiol. Jun;294(6):L1035-42.2008 [PMID: 18326826].

13.  Murphy, J., Summer, R., Wilson, A., Kotton, D., Fine, A. The Prolonged Life-span of Alveolar Macrophages Am J Respir Cell Mol Biol. 2008 Apr;38(4):380-5. 2008. [PMID: 18192503].

14.  Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, Kihara S, Walsh K. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007 Feb;117(2):375-86 [PMID: 17256056].

Lab Members

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Freddy Romero, PhD

Dr Freddy Romero is a trained biochemist. He received his Ph.D. from the Venezuelan Institute for Scientific Research where he investigated the effects of oxidative stress on kidney function. Dr Romero completed his post-doctoral training at Brigham and Women's Hospital in Boston before returning to Venezuela to run his own laboratory. Dr Romero was recently recruited back to the United States to join Dr Ross Summer's laboratory at Thomas Jefferson University. Dr Romero will be applying his expertise in biochemistry to study the role of surfactant lipids in lung homeostasis and disease.

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Dilip Shah, PhD

Dr. Dilip Shah's scientific effort is focused on the immunological aspect of diseases. He received his Ph.D. in Immunology from India where he studied the impact of oxidative stress in cytokine/chemokine imbalance and apoptosis in systemic lupus erythematosus. Dr. Shah recently completed his post-doctoral training at Massachusetts General Hospital in Boston where he worked on developing a novel laser-based vaccine adjuvant to enhance vaccine-induced immune responses. Dr. Shah now joins the laboratory of Dr. Ross Summer to study the immunological effects of obesity on lung function.

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Will Stafstrom

Will received his BA in Biology in 2012 from Bowdoin College in Brunswick, Maine