Professor of Medicine
Contact Information
Summary of Academic Program:
Pathogenesis and management of chronic rejection/obliterative bronchiolitis
Long-term outcomes after lung transplantation are frequently limited by the development of chronic rejection, which is manifested clinically by progressive airflow obstruction and histologically by obliterative bronchiolitis (OB). Our laboratory has conducted human and animal research studies related to OB pathogenesis during the past decade.
In 1992, we demonstrated a novel finding of increased concentrations of platelet-derived growth factor (PDGF) in bronchoalveolar lavage (BAL) fluid from lung transplant recipients with OB compared to healthy recipients. (1) Studies from other laboratories have subsequently demonstrated measurable increases in other cytokine and growth factor gene expression in OB.
Presently, we are collaborating with Dr. Richard King, Genetics Division, Department of Medicine to use high throughput gene expression microarray technology to identify patterns of peripheral blood mononuclear cell and BAL cell gene expression which are characteristic of acute and chronic lung rejection. Since 2002, this work has been funded by an NIH/National Institute of Allergy and Infectious Disease Program Project Grant (PPG) to study chronic rejection after lung transplantation; Dr. Hertz is the overall Principal Investigator of this PPG. Dr. Hertz also collaborates with Drs. Chris Wendt and Gary Nelsestuen, who are working to identify new protein biomarkers of lung rejection using state-of-the-art technology.
In 1993, we published the initial description of a heterotopic murine tracheal transplant model of OB, which has subsequently been adopted by investigators worldwide. (2) In collaboration with Dr. Daniel Mueller, Division of Rheumatology, Department of Medicine, we recently published an initial description of T-cell requirements for development of airway obliteration in this model. (3) Dr. Mueller's continuing work, also supported as a project on Dr. Hertz’ PPG proposes to use utilize heterotopic tracheal allotransplantation in mice to investigate cooperation between directly alloreactive CD8+ T cells and the self-MHC-restricted CD4+ T cells that respond against minor transplantation antigens in chronic allograft rejection.
Dr. Hertz has had a decade-long collaboration with Dr. Stanley Finkelstein, Department of Laboratory Medicine and Pathology, to use home-monitoring of symptoms and physiologic parameters to track the status of lung transplant recipients. We have demonstrated that home pulmonary function monitoring can allow early detection of physiologic changes of OB. (4) The home monitoring studies are currently funded by an NIH-RO1 (S. Finkelstein, PI).
Clinical scholarship related to lung transplantation
Dr. Hertz has contributed steadily to the clinical lung transplant literature during the past 15 years. He has recently published several major review articles related to OB; a clinical trial of a new approach to cytomegalovirus infection after lung transplantation; and original observations related to community respiratory virus infections in lung transplant recipients. He also has led a project to improve the knowledge base of house staff and referring physicians caring for lung transplant recipients; this has culminated in publication of a Manual of Lung Transplant Medical Care (2nd edition published in 2001).
Research Support
NIH (NINR) Stan Finkelstein (PI) 7/1/05-6/30/09
5R01NR009212 Role: Co-Investigator
Informatics based nurse triage in lung transplant care
NIH-NHLBI-R01 Christine Wendt (PI) 4/1/06-3/31/11
1R01-HL080041-01A2 Role: Co-Investigator
Protein Biomarkers in Lung Allograft Rejection
NIH Baolin Wu (PI) 4/10/07-3/31/11
R01GM083345-01A2 Role: Co-Investigator
Statistical Model Building for High Dimensional Biomedical Data
MMF Marshall Hertz (PI) 4/0108-3/31/09
Role: PI
Gene Expression Biometrics in Lung Transplant
NIH Marshall Hertz (PI) 4/1/08-3/31/13
Role: PI In Revision
Bronchoalveolar Lavage Cell Biomarkers in Lung Rejection
Selected Recent Publications.
Canales M, Youssef P, Spong R, Ishani A, Savik K, Hertz M, et al. Predictors of chronic kidney disease in long-term survivors of lung and heart-lung transplantation. Am J Transplant 2006;6(9):2157-63.
Lande JD. Patil J. Li N. Berryman TR. King RA. Hertz MI. Novel insights into lung transplant rejection by microarray analysis. Proc Am Thorac Soc. 2007; 4(1):44-51.
Adam TJ. Finkelstein SM. Parente ST. Hertz MI. Cost analysis of home monitoring in lung transplant recipients. Int J Tech Assessment in Health Care. 2007; 23(2):216-22.
Prekker ME. Herrington CS. Hertz MI. Radosevich DM. Dahlberg PS. Early trends in PaO(2)/fraction of inspired oxygen ratio predict outcome in lung transplant recipients with severe primary graft dysfunction. Chest. 2007; 132(3):991-7.
Trulock EP. Christie JD. Edwards LB. Boucek MM. Aurora P. Taylor DO. Dobbels F. Rahmel AO. Keck BM. Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report. J Heart Lung Transplant. 2007; 26(8):782-95.
Whitson BA. Prekker ME. Herrington CS. Whelan TP. Radosevich DM. Hertz MI. Dahlberg PS. Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant. 2007; 26(10):1004-11.
Lande JD, Patil J, Li N, Berryman TR, King RA, Hertz MI. Bronchoalveolar lavage cell gene expression in acute lung rejection: Development of a diagnostic classifier. Transplantation 2008: In press.
Zhang Y, Nelsestuen GL, Wendt CH, Hertz MI, Wu B. Early detection of lung transplant chronic rejection using regression model and BALF MALDI-TOF protein profiles. 2008, Submitted to Molecular and Cellular Proteomics.
Last Updated 04/17/08
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