The long term objectives of this project is to develop a multidisciplinary career development program that will equip new MD and PhD investigators with the knowledge and skills to identify mutations that cause or predispose to lung diseases and to elucidate the roles of the affected genes in the etiology and pathogenesis of the diseases. This Program will emphasize the genetics and genomics of lung development, and in particular genes that encode components of signaling pathways that control important steps in the lung development program, and how defects in such genes and pathways can cause or contribute to lung disease. The program will train Scholars in state-of-the-art technologies in mouse as well as human genetics and genomics to allow them to move back and forth between a tractable model genetic organism [mouse) where they can more easily identify new components of pathways and determine their functions in ung development and disease, and the more challenging but clinically important human genetic and genomic studies. The Program has three major components. The first is a one-year core curriculum of graduate classes in genetics and genomics that will provide Scholars with the necessary background and conceptual and technical framework for research in this field. The second is a didactic research curriculum that supplements the coursework during the first year and provides practical and ethical information and training for carrying out this type of research to Scholars. The third part is a mentored research project carried out in the second and third years using a genetic or genomic approach in mouse or in human patient samples to identify or characterize genes in a signaling pathway and their roles in lung development and disease. Upon completion of the Program, Scholars will be equipped with the tools to carry out on their own genetic and genomic experiments aimed at identifying disease genes and their roles in pulmonary diseases and obtaining independent funding for such research. Relevance: This program will provide new investigators with the knowledge and skills to discover genes that cause or contribute to lung disease and thereby lead to new ways of diagnosing and potentially treating patients with those diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (Program) (PSA) (K12)
Project #
5K12HL089989-03
Application #
7664318
Study Section
Special Emphasis Panel (ZHL1-CSR-A (S1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2007-09-27
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$399,600
Indirect Cost
Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Zamanian, Roham T; Hedlin, Haley; Greuenwald, Paul et al. (2018) Features and Outcomes of Methamphetamine-associated Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 197:788-800
Blum, Lisa K; Cao, Richard R L; Sweatt, Andrew J et al. (2018) Circulating plasmablasts are elevated and produce pathogenic anti-endothelial cell autoantibodies in idiopathic pulmonary arterial hypertension. Eur J Immunol 48:874-884
Spiekerkoetter, Edda; Sung, Yon K; Sudheendra, Deepti et al. (2017) Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension. Eur Respir J 50:
Orcholski, Mark E; Khurshudyan, Artyom; Shamskhou, Elya A et al. (2017) Reduced carboxylesterase 1 is associated with endothelial injury in methamphetamine-induced pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 313:L252-L266
Chang, Andy J; Ortega, Fabian E; Riegler, Johannes et al. (2015) Oxygen regulation of breathing through an olfactory receptor activated by lactate. Nature 527:240-4
Spiekerkoetter, Edda; Sung, Yon K; Sudheendra, Deepti et al. (2015) Low-Dose FK506 (Tacrolimus) in End-Stage Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 192:254-7
Shin, Kunyoo; Lim, Agnes; Zhao, Chen et al. (2014) Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 26:521-33
de Jesus Perez, Vinicio A; Yuan, Ke; Lyuksyutova, Maria A et al. (2014) Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 189:1260-72
Spiekerkoetter, Edda; Tian, Xuefei; Cai, Jie et al. (2013) FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 123:3600-13
Ayala, Estela; Kudelko, Kristina T; Haddad, Francois et al. (2012) The intersection of genes and environment: development of pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia and stimulant exposure. Chest 141:1598-1600

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