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Geoffrey Chupp, MD

Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine )
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Additional Titles

Director, Yale Center for Asthma and Airways Disease (YCAAD), Pulmonary, Critical Care & Sleep Medicine

Director, Pulmonary Function Laboratory, Yale-New Haven Hospital, Pulmonary, Critical Care & Sleep Medicine

Contact Info

Pulmonary, Critical Care & Sleep Medicine

PO Box 208057, 300 Cedar Street

New Haven, CT 06520-8057

United States

About

Titles

Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine )

Director, Yale Center for Asthma and Airways Disease (YCAAD), Pulmonary, Critical Care & Sleep Medicine; Director, Pulmonary Function Laboratory, Yale-New Haven Hospital, Pulmonary, Critical Care & Sleep Medicine

Biography

After graduating from Tufts University and the George Washington School of Medicine, Dr. Geoffrey Chupp completed a residency in Internal Medicine at the Tufts University School of Medicine and a Pulmonary and Critical Care Medicine Fellowship at Boston University School of Medicine. In 1997 Dr. Chupp came to Yale in 1997 and developed the Yale Center for Asthma and Airways Disease. This multifaceted program is a multidisciplinary clinical program that focuses on the care of patients with severe as and other complicated airways diseases, a center for translational research in airways disease, and a center where patients can participate in cutting edge industry sponsored research trials. The success of YCAAD has recently been realized with the publications on novel observations on chitinases in patients with asthma recruited from this multidisciplinary center.

Appointments

Other Departments & Organizations

Education & Training

MA
Yale University, Privatim (2017)
Fellow
Boston University School of Medicine (1997)
Resident
Tufts University/New England Medical Center (1993)
Intern
Tufts-New England Medical Center (1991)
MD
George Washington University (1990)
BS
Tufts University (1986)

Research

Overview

Yale Center for Asthma and Airways Disease (YCAAD) Research Program

Yale-New Haven Hospital is the largest referral center in the state and YCAAD is the only dedicated adult asthma center in the region. This active, rapidly growing center receives over 3000 visits a year and is the hub of the clinical/translational research program at Yale. Dr. Geoffrey Chupp, has directed YCAAD and developed a clinical research protocol, The Mechanisms and Mediators of Asthma and COPD (HIC 12268), that has recruited over 400 airway disease subjects to donate specimens to the YCAAD sample repository and participate in YCAAD research activities. The evolution of this research protocol, dovetailed with the clinical program, is a unique system that efficiently recruits subjects into clinical study protocols. These subjects have been recruited in YCAAD and are drawn from a large population of patients that continue to visit the center on a regular basis for long term care of their asthma. This allows for repeat sampling, thus enabling our active pursuit of longitudinal studies. In addition, many of these patients are seen during exacerbations in YCAAD or Yale-New Haven Hospital where exacerbation samples can be taken. From this protocol has grown a large sample repository of clinical and physiologic data, DNA, plasma and lung specimens from asthmatics that are stable or flaring (including the intensive care unit). All of this data is uploaded into a web-based database so that information enters the system in real-time.

YKL-40 Expression is Elevated in the Circulation and Lung of Severe Asthmatics

Once we had established the YCAAD research protocol and recruited an adequate number of patients, we began to search for clinically-practical biomarkers for asthma, focusing on the chitinase-like protein, YKL-40, based on the fact that its murine homologue is induced by interleukin (IL)-13 and it is measurable in the serum. We hypothesized that YKL-40 expression would be increased in asthmatics compared to normal individuals. We also hypothesized, although asthma is traditionally considered an organ-specific disease, that YKL-40 levels in the peripheral circulation would discriminate asthmatic severity. YKL-40 was readily appreciated in the serum from normal volunteers and was significantly higher in the serum from asthmatics [median (interquartile range) 58.3 ng/ml (40.0-73.3) versus 69.7 (40.0-107.1), P=0.02]. Importantly, YKL-40 levels increased with disease severity, with the highest levels observed in refractory asthmatics, compared to moderate and mild asthmatics, respectively (P for trend = 0.003). The median (interquartile range) YKL-40 level in mild asthmatics was 49.11 ng/ml (36.7-94.2), 68.43 ng/ml (38.0-88.0) in moderate asthmatics, and 77.0 (44.6-158.4) in severe asthmatics.
Based on the findings above, it was clear that circulating YKL-40 levels are elevated in asthmatics and, importantly, in severe asthmatics. The levels of YKL-40 also correlated with the expression in the lung and physiologic and pathologic measurements of airway remodeling. This suggested an important role for YKL-40 in the pathobiology of asthma, however, it remained unclear where YKL-40 played its part in the causal pathway and/or does it play a role in modulation of the asthmatic inflammatory response? To address this critical question in humans we hypothesized that genetic variation in the YKL-40 gene (CHI3L1) would influence circulating YKL-40 levels and would be associated with asthma. We thus pursued studies in collaboration with Dr. Carole Ober at the University of Chicago. In these studies, three additional asthma populations were examined, a well characterized founder population of European descent--the Hutterites (a related 13-generation, 1,623-person pedigree), 3 outbred Caucasian populations from the Childhood Origins of ASThma (COAST) birth cohort study, and 2 outbred asthma case-control populations from Freiberg Germany, and Chicago. These studies confirmed our findings in the YCAAD cohort and demonstrated that a polymorphism in the core promoter region of the CHI3L1 gene is associated with YKL-40 levels and with asthma, lung function and bronchial hyperresponsiveness. Now that we have confirmed that CHI3L1 is important in the pathogenesis of asthma, through the molecular phenotyping of lung disease grant Dr. Chupp is the Principle Investigator of, we will begin to dissected the pathobiologic differences in gene expression between individuals with different CHI3L1/YKL-40 genotypes and phenotypes and the impact that these changes have on the risk of asthma and asthma severity. Below is a brief description of the recently awarded phenotyping grant that will study 200 asthmatics for the next two years and will simultaneously measure genome-wide expression of genes in the blood and induced sputum using novel techniques developed in Dr. Chupp’s lab.

Molecular Phenotpying in Asthma Severity and role of Chitinase-3-Like-1 and YKL-40 Genotypes/Phenotypes (RO1-08-006)

We have developed a detailed clinical protocol and will be bringing patients into YCAAD for simultaneous blood and induced sputum sampling with a goal of furthering our understanding of severe asthma and the role of chitinases in asthma. Thus far, the human studies showed that YKL-40 is expressed in exaggerated quantities in the serum of asthma and correlates positively with asthma severity and airway remodeling, but inversely with lung function in multiple asthma populations. The genetic studies demonstrated that YKL-40 levels are associated with a functional polymorphism in the promoter of the CHI3L1 gene and with asthma status, bronchial hyperresponsiveness, and inversely with lung function. Therefore, YKL-40 is not only elevated in asthma, but also appears to part of the pathogenesis of asthma, at least in some patients. Another important observation we have made from these data is that the rs4950928 CC genotype is associated with the highest levels of circulating YKL-40 and nearly all these individuals are severe asthmatics. Furthermore, the frequency of the CC genotype increases with greater asthma severity. Lastly, using a strategy outlined in this proposal to evaluate gene transcription in the circulation, we have found (consistent with all our other results) that CHI3L1 gene expression is elevated in peripheral blood cells in asthmatics compared to controls and that GWAS analysis of individuals with high expression levels of CHI3L1 have identified a number of novel genetic associations will be investigated/validated with collaborators in other asthma populations. We have also demonstrated that relatively small changes in protein and gene expression in the circulation, while at first glance may seem unimportant biologically, when properly validated can identify novel molecules related to asthma pathogenesis. We believe that examining asthma severity using a similar strategy (relative to rs4950928 genotype, YKL-40 levels) will define unique expression profiles, molecules, and polymorphisms that will define specific phenotypes of asthma severity. Asthma Severity YKL-40 CHI3L1 gene.1. Molecular Phenotyping of Asthma Severity: In this project we are characterizing 200 asthmatics and collecting induced sputum and peripheral blood for genome-wide expression profiling to identify gene profiles that associated with asthma severity and common to both the peripheral blood and lung.

2. Gene expression profiles associated with CHI3L1 genotypes and YKL-40 levels in asthma: From the population described above, we are determining the biologic pathways associated with genetic polymorphisms we have determined are associated with asthma and asthma severity.

3.Expression profiles associated with responsiveness to Xolair. Using the profile we have developed for the gene expression study, we will determine the gene profiles that altered in response to treatment with Xolair.

Medical Subject Headings (MeSH)

Asthma; Bronchial Diseases; Bronchiectasis; Ciliary Motility Disorders; Lung Diseases; Pulmonary Medicine; Respiratory Tract Diseases

Research at a Glance

Yale Co-Authors

Frequent collaborators of Geoffrey Chupp's published research.

Publications

2024

Clinical Trials

Current Trials

Academic Achievements & Community Involvement

  • honor

    Yale Technology Summit: Technology Innovations Pitch Competition Award Second Place

  • honor

    Connecticut Magazine Top Docs 2016

  • honor

    Connecticut Magazine Top Docs 2015

  • honor

    Hero of Yale New Haven Hospital Award

  • honor

    Distinguished Service Award

Clinical Care

Overview

Geoffrey Chupp, MD, is a pulmonologist who specializes in lung diseases that affect the airway, including severe asthma, Chronic Obstructive Pulmonary Disease (COPD), bronchiolitis, autoimmune airway diseases, and airway diseases that have not been classified. He also specializes in eosinophilic lung diseases such as eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis (EGPA), and Allergic Bronchopulmonary Aspergillosis (ABPA).

He often helps patients who have complex disease that has been difficult to treat.

“I wanted to pursue a career in medicine to comfort people who are sick and discover the cause or causes of their disease,” says Dr. Chupp. Working with pulmonary patients is especially rewarding for a doctor, he adds. “It crosses all segments of society, so I get to meet lots of interesting people.”

Dr. Chupp came to Yale in 1997 and developed the Yale Center for Asthma & Airways Disease (YCAAD), a multidisciplinary clinical program that he still directs. The center cares for a broad spectrum of conditions and has helped patients with conditions that are difficult to diagnose, sometimes because of a co-occurring illness such as gastroesophageal reflux or sinusitis, and provides treatments that may not be available elsewhere. “We have novel biologic treatments and access to clinical trials for these patients,” he says.

Up to 20 clinical trials are active at any given time at YCAAD. This research has helped put Yale Medicine on the cutting edge of individualized asthma therapy and precision medicine for patients with asthma. “We see a future where we will be identifying a patient’s particular genetic risk factors and the molecular signals that are driving their particular disease,” says Dr. Chupp. “We will develop a combination of treatments that is personalized for every patient; it will include lifestyle recommendations, inhaled therapies, and biologic therapies that will maximally manage their disease without guesswork.”

Clinical Specialties

Pulmonology & Sleep Medicine; Asthma ; Pulmonary Critical Care

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Contacts

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Appointment Number
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Mailing Address

Pulmonary, Critical Care & Sleep Medicine

PO Box 208057, 300 Cedar Street

New Haven, CT 06520-8057

United States

Locations

  • The Anlyan Center

    Academic Office

    300 Cedar Street, Ste S441B

    New Haven, CT 06519

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