PHA Proof of Concept Research Grant Winner 2012

Yen-Rei Yu, MD, PhD

Yen-Rei Yu, MD, PhD

Department of Medicine, Division of Pulmonary and Critical Care Medicine
Duke University School of Medicine, Durham
Title: "The Role of Resident Monocytes in the Pathogenesis of Pulmonary Arterial Hypertension"
Term: January 15, 2013 through January 14, 2014

Summary of Research Project:

Despite recent advances in therapy, pulmonary arterial hypertension (PAH) still causes significant impairment in quality of life and mortality. Identification of new strategies that prevent or treat the disease are needed. Inflammation is a prominent feature of PAH, but little is known about the exact immune cell types and their roles in PAH development and progression.

Resident monocytes are present in tissue under normal state and are thought to be important for monitoring the health of the blood vessels and tissue. They play an important role in the repair of injured tissue. We expect that they have a significant role in PAH development but their functions have not been examined directly. Since little is known about the role of monocytes in PAH disease process, additional insights are needed prior to development of safe and effective monocyte-directed therapy.

In other diseases, such as cancer, researchers are accessing the benefits of therapies that target monocytes, a type of immune cells. Similar strategies may be applied to improve the quality of life or reduce mortality in PAH patients. We have proposed to examine the role of monocytes in PAH with a long term goal of defining key regulatory factors and aid in designing monocyte-directed therapeutic strategies. Not only will the proposed studies advance our understanding of monocytes; more importantly, they will advance our insights into PAH disease process and contribute to making monocyte-directed therapy a reality.

Curriculum Vitae

NAME: Yen-Rei Yu, MD, PhD
POSITION TITLE: Medical Instructor, Division of Pulmonary and Critical Care Medicine, Duke University School of Medicine

EDUCATION/TRAINING

Institution/Location Degree Year(s) Field of Study
Duke University School of Medicine, Durham, N.C. Fellowship 2008-2012 Pulmonary/Critical Care
Massachusetts General Hospital, Boston, Mass. Residency 2005-2008 Internal Medicine
Duke University School of Medicine, Durham, N.C. MD 1997-2004  
Duke University Graduate School, Durham, N.C. PhD 1999-2004 Immunology
Duke University Trinity College, Durham, N.C. BS 1993-1997 Biology, Magna cum Laude


BOARD CERTIFICATIONS/ELIGIBILITY

  • Internal Medicine, 2008
  • Pulmonary, 2010
  • Critical Care, Eligible

RESEARCH
Pulmonary and Critical Care, Medical Instructor, 2012-Present
Duke University School of Medicine, Durham
Michael Gunn, M.D. Role of monocytes in pathogenesis of pulmonary arterial hypertension

Pulmonary and Critical Care Medicine Fellowship, 2008-2012
Duke University School of Medicine, Durham
Michael Gunn, M.D.  CCR2 deficiency, Notch Signaling dysregulation, and spontaneous pulmonary arterial hypertension.

Postdoctoral Fellowship, 2005
University of North Carolina, Chapel Hill
Dhavalkumar Patel, MD.PhD.  Determine the role of CX3CR1 cytoplasmic-terminus on regulating CX3CR1-mediated signaling, adhesion, and chemotaxis.

Ph.D. Candidate, 1999-2004
Duke University School of Medicine, Durham
Dhavalkumar Patel, MD, PhD.  Thesis:  Biological Functions of CX3CR1: Regulation of Natural Killer cells and CX3CR1 functions.

Research Assistant, 1996-1997
Duke University School of Medicine, Durham
Jonathan Cohn, MD.  Elucidate the regulative role for Src kinases in Cystic Fibrosis Transmembrane Receptor (CFTR) signaling.

Research Assistant, 1994-1996
Duke University Trinity College, Durham
David McClay, Ph.D. Define the role for Cadherin and β-Catenin in cellular polarization during early sea urchin embryogenesis.

Research Assistant, 1993-1995
Duke University School of Medicine, Durham
Terry Harville, MD, PhD. and Rebecca Buckley, MD.  Determine the clonality of transplacentally-acquired maternal T lymphocytes in patients with severe combined immunodeficiency (SCID). 

Research Assistant, 1993 to 1994
Duke University Trinity College, Durham
Humanities Computing Facility.  Developed electronic dictionary for rare Chinese characters

PUBLICATIONS

  1. Yu, Y.R., Mao L., Piantadosi C.A., Gunn, M.D., CCR2 deficiency, Dysregulation of Notch Signaling, and Spontaneous Pulmonary Arterial Hypertension. 2013. Respiratory Cell and Molecular Biology. In Press.
  2. Liu, P., Yu, Y.R., Spencer, J.A., Johnson, A.E., Vallanat, C.T., Fong, A.M., Patterson C., Patel, D.D.  CX3CR1 Deficiency Impairs Dendritic Cell Accumulation in Arterial Intima and Reduces Atherosclerotic Burden. 2008. Arteriosclerosis, Thrombosis, and Vascular Biology.  28:243-250.
  3. Yu, Y.R., Fong, A.M, Cambadiere, C., Gao, J., Murphy, P.M,   and Patel, D.D.  Defective anti-tumor responses in CX3CR1-deficient mice. 2007. International Journal of Cancer. 121:316-22.
  4. Yu, Y.A., Fong, A.M., Patel D.  Mutational analysis of CX3CR1 functional regulation by the c-terminus.  2001.  FASEB Journal. 15: A360.
  5. Fong, A.M., Premont, R.T., Richardson, R.M., Yu, Y.R., Lefkowitz, R.J., and Patel, D.D. 2002. Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proceedings of the National Academy of Sciences of the United States of America. 99:7478-7483.
  6. Harrison, J.K., Fong, A.M., Swain, P.A., Chen, S., Yu, Y.R., Salafranca, M.N., Greenleaf, W.B., Imai, T., and Patel, D.D. 2001. Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion. Journal of Biological Chemistry. 276:21632-21641.

HONORS/ AWARDS
Scholarships and Funding, 1993-2013

  • Pulmonary Hypertension Association Proof-of-Concept Grant Award, 2013
  • Mandel Cardiovascular Fellowship, 2013
  • NIH Pulmonary Training Grant, 2009-2011
  • Senior Student Merritt Scholarship (William G. Anlyan), Duke School of Medicine, 2004        
  • NIH Immunology Training Fellowship, 1999-2001
  • Koo’s Foundation, Xi-Lai Academic, Westlake Polymer Merritt Scholarships, 1993-1998    
  • Sigma Xi Research Grant, Undergraduate Research Grant, 1995-1997
  • Howard Hughes Research Fellow, 1994    

Awards and Honors for Oral and Poster Presentations, 1999-2012

  • American Thoracic Society Poster Presentation, 2011    
  • International Congress of Immunology Conference (ICI), 2004
  • Federation of Clinical Immunology Societies (FOCIS) Center of Excellence Symposium, 2004
  • Gordon Research Conference Invitation for poster presentation, 2003    
  • Federation of American Societies for Experimental Biology (FASEB), 2001
  • Bernard Amos Poster Competition. First place, 2001
  • Chrysalis Project of American Academy of Allergy, Asthma, and Immunology (AAAI), 1999

Distinctive Dean’s List and Dean’s List, 1993-1997
Golden Key’s Honor Society, Present

Phi Beta Kappa Honor Society, Present

American Thoracic Society, Present

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