PHA/AHA Post Doctoral Fellowship Award Winner 2011

Salina Gairhe, BSC, MSc, MScSalina Gairhe, BSC, MSc, MSc, PhD

University of South Alabama, Mobile
“Sphingosine 1 Phosphate Mediates Sustained Vasoconstriction in Pulmonary Arterial Hypertension”
July 1, 2011 – June 30, 2013

 
Summary of Research Project:

1. What is the major problem being addressed by this study?
Pulmonary hypertension is a debilitating disease with no effective therapeutic option. Current medical treatment improves symptoms and survival, but the morbidity and mortality remains unacceptably high. This suggests that cellular and molecular pathogenic mechanisms of PAH is neither been identified nor therapeutically targeted. A major hallmark of PAH are sustained vasoconstriction, arterial wall thickening, and in situ thrombosis. There is substantial evidence that the sustained pulmonary vasoconstriction is due predominantly to RhoA/Rho kinase-signaling. This study will address that phospholipid, sphingosine-1-phosphate (SIP) is an upstream mediator of Rho kinase signaling that promotes pulmonary vascular vasoconstriction associated with pulmonary arterial hypertension.

* 2. What specific questions are you asking and how will you attempt to answer them?
We will examine the possible role of S1P and its source in the sustained vasoconstriction and increased tone associated with PAH. We will use lungs perfused with saline and pulmonary arteries isolated from Sugen5416/hypoxia/normoxia rat model, the only rodent model of PAH that recapitulates human disease with plexiform lesions. First we will use pharmacologic inhibitors to determine the role of Rho kinase signaling in SIP-induced vasoconstriction. Second we will determine the source of S1P in PAH by performing similar studies using whole and depleted blood perfusates. Third, results from these studies will be used to direct in vivo studies that will administer anti-S1P agents to PAH rats and examine vasodilator effects.

* 3. What is the long-term biomedical significance of your work, particularly as it pertains to the cardiovascular area? What major therapeutic advance(s) do you anticipate that it will lead to? For instance, new drug(s), a surgical technique/procedure, a diagnostic tool/test, a previously undetected risk factor, etc.
There is limited ability to effectively improve survival of patients with PAH and the molecular mechanism linked with pulmonary artery dysfunction is poorly understood. If the results of the study are positive, this would provide insight into whether S1P signaling contributes to sustained vasoconstriction and increased tone associated with PAH via Rho kinase activation. Positive results will stimulate considerable additional research to determine if S1P signaling pathway is also important in the pathogenesis of human PAH and, if so, the mechanisms of its regulation can be therapeutically

Curriculum Vitae

NAME: Salina Gairhe
POSITION TITLE: Post Doctoral Research Fellow

EDUCATION/TRAINING
INSTITUTION AND LOCATION   DEGREE   YEAR(s)   FIELD OF STUDY
Tribhuvan University, Kathmandu, Nepal   Bachelor of Science   1997-2000   Microbiology
Tribhuvan University, Kathmandu, Nepal   Masters of Science   2000-2002   Microbiology
Eastern Illinois University, Charleston, IL   Masters of Science   2004-2006   Neuroscience
University of South Alabama, Mobile, AL   PhD   2006-2011   Pharmacology/Lung biology
             

POSITIONS

  • Dec 2001 - May 2004, Part-time Instructor, Institute of Community Health, Kathmandu, Nepal.
  • May 2003 - July 2004, Microbiologist,Health Care Foundation-Nepal, National Kidney Center, Kathmandu, Nepal.
  • May 2004 - Aug 2004, Intern, United Nations Development Program, Global Environment Facility, Small Grant Program, Kathmandu, Nepal.
  • Fall 2004 - Summer 2005 & Summer 2006 Graduate Research Assistant, Biological Science Department, Eastern Illinois University, Charleston, IL.
  • Fall 2005 - Spring 2006, Graduate Teaching Assistant, Biological Science Department, Eastern Illinois University, Charleston, IL.
  • Fall 2006 - Spring 2011, Graduate Research Assistant, Department of Pharmacology & Center for Lung Biology, University of South Alabama, Mobile, AL.
  • August 2008 - 2010, Student Representative, Center for Lung Biology, Basic Medical Science Student Organization, University of South Alabama, Mobile, AL.
  • Summer 2009 - Instructor, Biomedical Enrichment and Recruitment (BEAR) Program, Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, AL.
  • Spring 2011 - Instructor, "Professional Presentation Skill", Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, AL.
  • Spring 2011 - Preceptor, Simulation Lab, Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL.

AWARDS AND HONORS

  • 2001, Honors Diploma, Web page designer, National Web College,Nepal.
  • 2004 - 2006, International Student Scholarship, Eastern Illinois University, Charleston, IL.
  • 2009,First Position,10 Minutes Talk, Graduate Student Speaking Competition, University of South Alabama, Mobile, AL.
  • 2009, Outstanding graduate student award, University of South Alabama, Mobile, AL.
  • Salina Gairhe
  • 2010, Travel Award, American Thoracic Society, University of South Alabama, Mobile, AL.

REVIEWER with Dr. IVAN McMURTRY

  • American Journal of Physiology
  • Journal of Applied Physiology
  • Journal of Comparative Physiology
  • Journal PLoS ONE

PRESENTATIONS AND CONFERENCES

  • 2002, Participated and presented a poster in the Seminar of Microbiology, Kathmandu, Nepal.
  • 2004, Participated and presented the paper in the second National Conference and Fourth General Assembly of Nepalese Society of Microbiology, Kathmandu, Nepal.
  • 2007, Poster: Impact of apo-E deficiency on regeneration of olfactory receptor neurons post injury in mice. Association for Chemoreception Sciences, XXIXth Annual Meeting.
  • 2007, Poster: Endothelial cell RhoA/ Rho kinase signaling regulated vascular smooth muscle phenotype. College of Medicine, University of South Alabama, Mobile, AL.
  • 2008, Poster: Effect of co-culture with pulmonary arterial endothelial cells (PAECs) on phenotype of pulmonary arterial smooth muscle cells (PASMCs). College of Medicine,University of South Alabama, Mobile, AL.
  • 2008, Talk: Research in Progress. Center for Lung Biology, University of South Alabama, Mobile, AL.
  • 2008, Talk: Research in Progress. Smooth Muscle group, Department of Physiology, University of South Alabama, Mobile, AL.
  • 2009, Poster: Effect of co-culture with pulmonary arterial endothelial cells (PAECs) on phenotype of pulmonary arterial smooth muscle cells (PASMCs). FASEB, New Orleans.
  • 2009, Training, RCR and Career Development Session, University of South Alabama, Mobile, AL.
  • 2009, Talk: Research in Progress. Center for Lung Biology, University of South Alabama, Mobile, AL.
  • 2009, Talk: Research in Progress. Smooth Muscle group, Department of Physiology, University of South Alabama, Mobile, AL.
  • 2009, Poster: Development of Cell Co-culture Model of Neointima Formation. College of Medicine, University of South Alabama, Mobile, AL.
  • 2010, Talk: Research in Progress. Smooth Muscle group, Department of Physiology, University of South Alabama, Mobile, AL.
  • 2010, Poster: TGF-β mediates myoendothelial gap junctional signaling-dependent differentiation of pulmonary arterial smooth muscle. ATS, New Orleans, 2010.
  • 2010, Poster: Hypoxia disrupts myoendothelial gap junctional signaling and causes dedifferentiation of pulmonary arterial smooth muscle cells co-cultured with pulmonary arterial endothelial cells. ATS, New Orleans, 2010.
  • 2010, Talk: Pulmonary arterial endothelial cell-derived serotonin passes through myoendothelial gap junctions to induce differentiation of pulmonary arterial smooth muscle cells. College of Medicine, University of South Alabama, Mobile, AL.

PROFESSIONAL SOCIETIES

  • National Microbiological Society, Kathmandu, Nepal, Life Member
  • Institute of Community Health, Kathmandu, Life Member
  • Advancing Science Serving Society, Member
  • American Heart Association, Member- Since 2008
  • American Physiological Society, Member-Since 2008
  • American Thoracic Society, Member-Since 2008

PUBLICATION

  1. Salina Gairhe. 2003. Microbial colonization of maternal genital tract and its relationship to onset of early neonatal sepsis. Tribhuvan University, Master’s Thesis.
  2. Salina Gairhe. 2006. Role of apolipoprotein E in neurogenesis, maturation and synaptogenesis in olfactory epithelium of mice. Eastern Illinois University, Master’s Thesis.
  3. Britto P. Nathan, Sreenivas Nannapaneni, Salina Gairhe, Ikemefuna Nwosu, and Robert G. Struble., 2007. The distribution of apolipoprotein E in mouse olfactory epithelium. Brain Research. March 16; 1137(1): 78–83.
  4. Ikemefuna Nwosu, Salina Gairhe, Robert G. Struble and Britto P. Nathan., 2008. Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb. Neuroscience Letters, Volume 441, Issue 3, Pages 282-285.
  5. Britto P. Nathan, Salina Gairhe, Ikemefuna Nwosu, Stephen Clark and Robert G. Struble., 2010. Reconstitution of the olfactory epithelium following injury in ApoE-deficient mice. Experimental Neurology. (In press)
  6. Salina Gairhe. September, 2010. Myoendothelial gap junctional signaling regulates pulmonary arterial smooth muscle cell phenotype. University of South Alabama, PhD. Dissertation.
  7. Salina Gairhe, Sarah Sayner, 2010. Did you know that woman with pulmonary arterial hypertension (PAH) have an elevated risk of mortality during pregnancy? Online article, Center for Lung Biology, University of South Alabama. “http://www.southalabama.edu/clb/index.htm”.
  8. Kohtaro Abe, Michie Toba, Abdallah Alzoubi, Karel Koubsky, Masako Ito,Hiroki Ota, Salina Gairhe, William T. Gerthoffer, Karen A. Fagan, Ivan F. McMurtry, and Masahiko Oka. Tyrosine kinase inhibitors are potent acute pulmonary vasodilators in rats. American Journal of Respiratory Cell and Molecular Biology, 2011. (In press)
  9. Salina Gairhe, Sarah Gebb, Ivan Fredrick McMurtry. Myoendothelial gap junctional signaling regulates pulmonary arterial smooth muscle cell phenotype. American Journal of Lung Physiology, 2011. (In press)
  10. Salina Gairhe, Ivan Fredrick McMurtry. Serotonin mediates myoendothelial gap junctional signaling-dependent differentiation of pulmonary arterial smooth muscle. Circulation Research, 2011. (Manuscript in progress)

ABSTRACTS

  1. Salina Gairhe, Natalie Bauer, William Grethoffer, Ivan Fredrick McMurtry. Effect of co-culture with pulmonary arterial endothelial cells (PAECs) on phenotype of pulmonary arterial smooth muscle cells (PASMCs). FASEB, New Orleans. 2009.
  2. Salina Gairhe and Ivan Fredrick McMurtry. Sub-Acute Hypoxia Disrupts Myoendothelial Gap Junctional Signaling and Causes Dedifferentiation of Pulmonary Arterial Smooth Muscle Cells Co-Cultured with Pulmonary Arterial Endothelial Cells. ATS, New Orleans, 2010.
  3. Salina Gairhe, Sarah Gebb, and Ivan Fredrick McMurtry.TGF- Mediates Myoendothelial Gap Junctional Signaling-Dependent Differentiation of Pulmonary Arterial Smooth Muscle. ATS, New Orleans, 2010.
  4. Karen A. Fagan, Salina Gairhe, Kohtaro Abe, Masahiko Oka, and Ivan F. McMurtry. Increased Fibronectin in an Animal Model of Severe Pulmonary Arterial Hypertension. ATS, New Orleans, 2010.
  5. Salina Gairhe, Sarah Gebb and Ivan Fredrick McMurtry. Serotonin Mediates Myoendothelial Gap Junction-Dependent Differentiation Of Pulmonary Arterial Smooth Muscle Cells. ATS, Denver. 2011.
  6. Karen A. Fagan, Kelland Williams, Salina Gairhe, Patricia Villalta, Masahiko Oka, Kohtara Abe, and Ivan F. McMurtry. Increased Expression of Alpha 5 and Beta1 Integrins in an Animal Model of Severe Pulmonary Arterial Hypertension. ATS, Denver. 20113

RESEARCH SUPPORT

Spring 11 Postdoctoral Fellowship (07/01/2011 to 06/30/2013)
Pulmonary Hypertension Association - American Heart Association, Greater Southeast Affiliate
“Sphingosine 1 Phosphate Mediates Sustained Vasoconstriction in Pulmonary Arterial Hypertension”

COMPLETED PROJECT

Ongoing Research Support
GSA Spring 09 Predoctoral Fellowship (07/01/2009 to 06/30/2011)
American Heart Association, Greater Southeast Affiliate
“Myoendothelial gap junction signaling regulates pulmonary vascular smooth muscle cell phenotype”

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