Pediatrics: Pulmonary and Sleep Medicine

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 Research

Researcher

The research programs in the Division of Pulmonary and Sleep Medicine reflect the broad range of interests of the group.  Researchers have participated in the Wisconsin Cystic Fibrosis Newborn Screening Project since 1985.  Dr. Hara Levy has funding from the National Institutes of Health (NIH) for her genetic and genomic investigation of cystic fibrosis (CF). 

In the sleep program, investigators have looked at mechanisms of upper airway obstruction in children with obstructive sleep apnea and management of upper airway obstruction with mandibular distraction in children with Pierre-Robin syndrome. 

Finally, investigators are looking at the epidemiology of rural asthma.


Current Faculty Researcher

Hara Levy, MD, MMSc

Hara Levy, MD Research
Pediatric Pulmonologist
Children’s Hospital of Wisconsin
Assistant Professor of Pediatrics
Medical College of Wisconsin

Investigator
Children’s Research Institute

Research Interests

Integrating Genetics and Genomics

The Levy lab focuses on integrating genetic and genomics to advance the understanding of the contribution of environmental, genetic, and epigenetic factors influencing the progression of cystic fibrosis (CF) lung disease. An understanding of the link between the CFTR gene defect, responsible for CF,  and functional impairment that leads to clinical sequelae should help in the development of cellular and molecular markers that are easily measured and predictive of therapeutic efficacy such as the restoration of the host defense function. This would allow for a direct link between gene expression and functional correlation applicable in CF and also more common chronic inflammatory lung diseases.

Currently, we are using the samples from the Wisconsin newborn screening project, as well as additional clinical samples from patients followed clinically at our CF centers, to identify non-invasive gene expression markers for CF by generating a genome-wide expression profile of serum samples from CF patients over time, thereby defining a unique expression signature as it correlates to infection status and lung function. Therefore, our research is helping to generate a unique molecular signature and associated risk established early in life providing unprecedented opportunity for novel prognostic and therapeutic interventions in CF and perhaps a model for other chronic inflammatory lung diseases.

Our studies further identify an innovative assay which could potentially define a pathogen specific response, provide data associated with disease phenotypes and support the use of an integrated approach to move beyond marker identification to mechanism discovery. Further, utilizing these microarray studies from our laboratory, we have confirmed the ability to use this technology for the identification of molecular signatures that track with genotype and clinical phenotype. Through this application, we have begun to harness the functional genomics infrastructure to longitudinally dissect molecular events in CF in response to infection status and integrate with genotyping in a manner not previously possible.

Our future goals include identification of a series of non-CFTR candidate genes through integration of functional genomics and genetics that may impact the severity of CF lung disease and account for phenotypic heterogeneity. We hope to further the development of a highly accurate, cost effective global gene expression profiling in CF that is sufficiently sensitive to address discrete biologic questions utilizing the integration of genomics and genetics.

Selected Publications:

  • Ly NP, Ruiz-Pérez B, Onderdonk A, Tzianabos AO, Litonjua AA, Liang C, Laskey D, Delaney ML, DuBois AM, Levy H, Gold DR, Ryan LM, Weiss ST, Celedón JC. Mode of delivery and cord blood cytokines: a birth cohort study. Clin Mol Allergy 2006;4:13. PMID: 17002791.

 

  • Levy H, Kalish LA, Huntington I, Weller N, Gerard C, Silverman EK, Celedón JC, Pier GB, Weiss ST. Inflammatory markers of lung disease in adult patients with cystic fibrosis. Pediatr Pulmonol 2007;42(3):256-62. PMID: 17245735.

 

  • Levy H, Kalish LA, Cannon CL, García KC, Gerard C, Goldmann D, Pier GB, Weiss ST, Colin AA. Predictors of Mucoid Pseudomonas Colonization in Cystic Fibrosis Patients. Pediatr Pulmonol 2008; 43(5):463-71. PMID:  18361452.

 

  • Levy H, Murphy AJ, Zou F, Gerard C, Klanderman BJ, Schuemann B, Lazarus R, García KC, Celedón JC, Drumm M, Dahmer MK, Quasney MW, Schneck K, Reske M, Knowles MR, Pier GB, Lange C, Weiss ST.  IL1-β polymorphisms modulate cystic fibrosis lung disease.  Pediatr Pulmonol 2009; 44 (6): 580-593. PMID: 19431193

 

  • Jadin SA, Wu GS, Zhang Z, Shoff SM, Tippets BM, Farrell PM, Miller T, Rock MJ, Levy H and Lai, HJ. Growth and pulmonary outcomes during the first two years of life of breastfed and formula-fed infants diagnosed with cystic fibrosis through the Wisconsin Routine Newborn Screening Program. The American Journal of Clinical Nutrition. May;93(5):1038-47. Epub 2011 Mar 23. PMID: 21430114.

 

  • Rock M J, Levy H, Zaleski C, Farrell P M. Factors Accounting for a Missed Diagnosis of Cystic Fibrosis  After Newborn  Screening.  Pediatr Pulmonol.  2011; 46(12):1166-74. PMID: 22081556.

 

  • Baughn  JM,  Quasney  MW,  Simpson  P,  Merchant  D,  Li  SH,  Levy  H,  Dahmer  MK. Association  of  CFTR  Gene  Variants  with  Acute  Lung  Injury  in  African  American Children with Pneumonia. Critical Care Medicine. 2012; 40(11):3042-9. PMID: 22890249. PMCID pending.

 

  • Sebro R*, Levy H*, Schneck K, Dimmock, D, Raby BA, Cannon, CL, Broeckel U and Risch NJ.  Cystic Fibrosis mutations for F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency. Clin Genet. 2012 Dec; 82(6):546-51. PMID:  22035343 (* indicates co-first authorship).

 

  • Levy H, Wang X, Kaldunski M, Jia S, Kramer J, Pavletich SJ, Reske M, Gessel T, Yassai M, Quasney MW Dahmer MK, Gorski J, Hessner MJ. Transcriptional signatures as a disease specific and predictive inflammatory biomarker.  Genes and Immunity. 2012 Dec; 13(8):593-604. PMID: 22972474. PMCID Pending.

Grant Support

  • Children’s Research Institute Ann Hardy Fund

Peer Review (funded):

  • NIH/ Office of the Director: “Integration of Genomics with Genetics-Molecular Phenotypes for CF Lung Disease” Principal Investigator
  • NIH/NHLBI: “IL-1 Family Gene polymorphisms and Susceptibility to P. aeruginosa in CF Patients”

Principal Investigator

  • NIH/NHLBI: “Pulmonary Benefits of Cystic Fibrosis Neonatal Screening”

Subcontract Principal Investigator (PI: Philip M. Farrell, Ph.D.)

  • NIH/NIDDK: “ Malnutrition and Lung Disease in Cystic Fibrosis”

Co-Principal Investigator (PI: HJ Lai, Ph.D.)

  • Juvenile Diabetes Research Foundation: “Serum Induced Transcriptional Signature in T1DM and its Relationship to CFDM” Co-Investigator (PI: Martin Hessner, Ph.D.)

Peer Review (council review):

  • NIDDK: “Efficacy of Tailored Family-Centered Genetic Counseling for Cystic Fibrosis” Co-Principal Investigator (PI: Audrey Tluczek Ph.D.)

Research Staff:

Melissa Reske Research Associate mtickner@mcw.edu


Contact Information
Phone: (414) 955-2379
Fax: (414) 266-6742
Email: hlevy@mcw.edu


Research Affiliations

  • The Children's Research Institute (CRI) advances state-of-the-art pediatric health care through translational research programs to find life-saving discoveries and cures in the disease that affect children and interventions that enhance quality of life for children and families living with chronic health conditions.
  • The National Institutes of Health (NIH) is the nation's medical research agency supporting scientific studies that turn discovery into health.
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