Dr. Golden received his B.A. degree from Yale
University in 1968 and his M.D. degree from Washington University in St.
Louis in 1972. He received both his internal medicine and pulmonary
subspecialty training at the University of California at San Francisco.
He completed his pulmonary research training at UCSF's Cardiovascular
Research Institute where he studied ozone inhalation in humans as a model
of asthma. Dr. Golden has been on the faculty in the Department of
Medicine since 1977 and is currently Director of the Bronchoscopy
Service, Medical Director of Lung Transplantation, and co-Director of the
Interstitial Lung Clinic.
Clinical Research Activities
Dr. Golden is involved primarily with clinical practice and clinical
research in three main areas of interest: bronchoscopy, interstitial
lung disease, and lung transplantation.
BRONCHOSCOPY –
Dr. Golden is expanding the use of transbronchial biopsy, for example in
intubated patients as well as its application as a research tool. He is
developing new techniques to improve the accuracy of transbronchial
needle aspiration biopsy. In collaboration with interventional radiology,
he is developing new methods and indications for airway stenting. Dr.
Golden has initiated studies to test the feasibility of endobronchial
lung volume reduction.
In collaboration with Dr. John Conte, he is employing lavage techniques
to study the pulmonary pharmacokinetics of new oral and intravenous
antibiotics such as ketolides in epithelial lining fluid.
INTERSTITIAL LUNG DISEASE –
The interstitial lung disease (ILD) clinic, which Dr Golden has
developed for over 25 years, includes 6 faculty members. The UCSF ILD
program was awarded a Center of Excellence Grant from the Department of
Medicine on which Dr Golden is a co-investigator. In 2005, the program
was selected to be one of 11 centers in the US to receive NIH
sponsorship for clinical research.
Dr Golden has been responsible for specific drug trials for idiopathic
pulmonary fibrosis (IPF) which include a completed initial study of
gamma interferon as well as ongoing studies with bosantan, a second
gamma interferon study, and also inhaled iloprost. In terms of
scleroderma-related lung disease, Dr Golden was the first person to
show that CellCept could improve lung function and diminish lung
inflammation in this disorder which has led to a funded study by Roche
to further investigate this compound in these patients. He is a
co-investigator in a NIH sponsored multi-center study of cytoxan for
scleroderma-related lung disease and has developed a novel sponsored
drug trial for scleroderma lung disease. Dr Golden is also
collaborating with Dr. Demarco investigating the benefit of Flolan
therapy for secondary pulmonary hypertension ILD.
In terms of mechanism of disease, Dr Golden is developing prospective
investigations re the role of esophageal dysmotility and benefit of
surgery in ILD patients. Further studies on mechanisms of ILD involve
Dr Golden's collaboration involving both surgical biopsy and lung
transplant explanted material with basic scientists. Dr Golden is
also a co-investigator with Dr. Chapman in understanding regulation
of integrin function in ILD using such tissue.
LUNG TRANSPLANTATION –
Dr Golden initiated the UCSF lung transplant program in 1991. Since
2002 it has become one of the top 10% in the world in terms of yearly
procedures. This spectacular growth has afforded more research in
lung transplantation as well as in interstitial lung disease, the
most common recipient diagnosis.
Lung transplant projects involve early detection of acute vascular
and/or chronic airway rejection (obliterative bronchiolitis, OB) such
as expiratory dynamic ultra-fast high-resolution CT scanning as a way
to predict impending OB. Dr Golden initiated a novel endobronchial
airway biopsy technique to assess early pathogenetic events leading to
airway rejection.
Other novel bronchoscopic approaches to investigate chronic airway
rejection include detecting increased fibroblast proliferative
activity in serial lavage fluid. Recently, in collaboration with Dr.
George Caughey, this observation was extended by profiling gene
expression using multiplex, real time PCR of serial lavage, bronchial
and transbronchial biopsies of human lung allografts. Certain
transcript profiles in lung allograft biopsies correlate with
lymphocytic bronchitis which precedes OB. We are also undertaking a
proteomic study, in collaboration with Dr. Weiner-Kronish, in serial
bronchoscopic-derived material to detect epithelial markers of injury
which could be predictive of OB. We are extending these bronchoscopic
observations by comparing evidence for the same biomarkers in the
blood.
To understand the role of infection in causing OB, Drs. Boushey, and
Ganem will undertake a genomics-based approach to virus identification
and discovery in post-transplant bronchiolitis, as well as in
pulmonary fibrosis, employing a microarray technique applied to our
archived bronchoscopic material. Other bronchoscopic based transplant
research involves investigating the role of certain genetically
characterized pseudomonas strains and their virulence determinants as
risk factors for OB, and a proteomic analysis of epithelial lining
fluid employing a novel bronchoscopic sponge to detect specific
proteins that constitute evidence of infection.
In terms of novel therapy for rejection, we are studying Rapamyacin, a
new anti-fibrotic immunosuppressant, in preventing chronic rejection.
Also, in collaboration with University of Pittsburgh, we will begin
assessing inhaled cyclosporine to prevent airway rejection.
SELECTED PUBLICATIONS
Ware LB, Golden JA, Finkbeiner WE, Matthay MA. Alveolar epithelial
fluid transport capacity is preserved in reperfusion lung injury after
lung transplantation. Am J Respir Crit Care Med
1999 Mar;159(3):980-988
Jonosono M, Fang KC, Keith FM, Turck CW, Blanc PD, Hall TS, Fukano A K,
Rifkin CJ, Gold WM, Webb WR, Edinburgh KJ, Finkbeiner WE, Golden JA.
Utility of measuring fibroblast proliferative activity in
bronchoalveolar lavage fluid in the early detection of obliterative
bronchiolitis in lung transplant recipients. J Heart Lung Transplant
1999 Oct; 18(10):972-85.
Henke JA, Golden JA, Keith FA, Yelin EH, Keith FA, Blanc PD. Persistent
increases of BAL neutrophils as a predictor of mortality following
lung transplant. Chest 1999;115(2):403-409.
Eisner, Gordon RL, Webb WR, Gold WM, Hilal SE, Edinburgh K, Golden JA.
Pulmonary function improves after expandable metal stent placement for
benign airway obstruction. Chest, 1999 Apr;115(4):1006-11.
Gotway MB, Lee ES, Reddy GP, Golden JA, Webb WR. Low-dose, dynamic,
expiratory thin-section CT of the lungs using a spiral CT scanner. J
Thorac Imaging. 2000 Jul;15(3):168-72
Lee ES, Gotway MB, Reddy GP, Golden JA, Keith FM, Webb WR. Early
bronchiolitis obliterans following lung transplantation: accuracy of
expiratory thin-section CT for diagnosis. Radiology. 2000
Aug;216(2):472-7
Chesnutt MS, Nuckton TJ, Golden JA, Folkesson HG, Matthay MA. Rapid
alveolar epithelial fluid clearance following lung lavage in
pulmonary alveolar proteinosis. Chest 2001; 120(1): 271-274
Gotway MB, Dawn SK, Sellami D, Golden JA, Reddy GP, Keith FM, Webb
WR. Acute rejection following lung transplantation: limitations in
accuracy of thin-section CT for diagnosis. Radiology. 2001
Oct;221(1):207-12
Gotway MB, Golden JA, LaBerge JM, Webb WR, Reddy GP, Wilson MW,
Kerlan Jr RK, Gordon RL. Benign tracheobronchial stenoses: changes
in short-term and long-term pulmonary function testing after
expandable metallic stent placement.J Comput Assist Tomogr.
2002;26(4):564-72.
Conte JE, Jr., Golden JA, McQuitty M, Kipps J, Duncan S, McKenna E,
and Zurlinden E. Effects of gender, AIDS, and acetylator status on
intrapulmonary concentrations of isoniazid. Antimicrob Agents
Chemother. 2002 Aug;46(8):2358-2364
Conte JE Golden JA Kipps JE Lin ET Zurlinden E. Effect of Sex
and AIDS status on the plasma and intrapulmonary pharmacokinetics of
rifampicin, Clin Pharmacokinet 2004; 43 (6): 395-404
Xu X, Golden JA, Dolganov G, Jones KD, Donnelly S, Weaver T, Caughey
GH. Transcipt Signatures of Lymphocytic Broncitis in Lung Allograft
Biopsies. J Heart Lung Transplant. In press
Thornton RH Gordon RL LaBerge JM Wilson MW Wolanske KA Gotway MB
Hastings G Golden JA. Outcomes of Tracheobronchial stenting for
benigh disease: A 10 year experience, submitted
