Marshall Hertz, MD

Professor of Medicine
Director, Center for Lung Science and Health
Medical Director, Lung Transplant Program
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).

Current Research Support

NIH-NHLBI                      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

NIH (NINR)               Stan Finkelstein (PI)           7/1/05-6/30/09
5R01NR009212                            Role:  Co-Investigator
Informatics-Based Nurse Triage in Lung Transplant Care

Apt Pharmaceuticals, Inc.    Marshall Hertz, PI     2008-2012
A multi-center, randomized, double-blind, placebo-controlled study to demonstrate the efficacy and safety of cyclosporin inhalation solution in improving bronchiolitic obliterans syndrome-free survival following lung transplantation.

Selected Recent Publications .

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; 85(2):224-31.

Yoon HJ, Guo H, Hertz MI, Finkelstein SM. Adherence to home-monitoring and its impact on survival in post-lung transplantation patients. AMIA Annu Symp Proc. 2008; 6:835-8.

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.

Hertz MI, Aurora P, Christie JD, Dobbels F, Edwards LB, Kirk R, Kucheryavaya AY, Rahmel AO, Rowe AW, Stehlik J, Taylor DO.  Scientific Registry of the International Society for Heart and Lung Transplantation: introduction to the 2009 annual reports.  J Heart Lung Transplant. 2009;28(10):989-92.

Taylor DO, Stehlik J, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Kucheryavaya AY, Rahmel AO, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult heart transplant report--2009. J Heart Lung Transplant, 2009;28(10):1007-22.

Christie JD, Edwards LB, Aurora P, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Taylor DO, Kucheryavaya AY, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult lung and heart/lung transplantation report--2009. J Heart Lung Transplant, 2009;28(10):1031-49.

Kirk R, Edwards LB, Aurora P, Taylor DO, Christie JD, Dobbels F, Kucheryavaya AY, Rahmel AO, Stehlik J, Hertz MI.  Registry of the International Society for Heart and Lung Transplantation: twelfth official pediatric heart transplantation report--2009. J Heart Lung Transplant2009;28(10):993-1006.

Aurora P, Edwards LB, Christie JD, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Taylor DO, Kucheryavaya AY, Hertz MI.  Registry of the International Society for Heart and Lung Transplantation: twelfth official pediatric lung and heart/lung transplantation report--2009. J Heart Lung Transplant, 2009;28(10):1023-30.