Meet the Expert

Learn what Dr. Phillips, a Senior Principal Scientist with over 25 years of experience in the field of repiratory drug delivery, has to say about the future of pulmonary drug discovery and his work!

Dr. Jonathan Phillips is a Principal Scientist and Global Discovery Research Lead for respiratory drug delivery at Amgen. He has over 20 years of experience in the field of respiratory drug delivery, and has been involved in the discovery and support of ground breaking compounds for diseases such as asthma, cystic fibrosis and COPD. 

 

Interview:

Q: What lead you to pursue this research area? What interests you the most about it?

I have been fortunate to work for the last 25 years in big pharma (Schering-Plough, Merck, Roche, and Amgen) where my lab discovers and validates new drug targets and develops drugs for respiratory diseases.  My thesis advisor in graduate school was a radiation physicist that developed a technique using radioactive (Tc-99m) iron colloid aerosols to visualize mucociliary clearance from human lungs in vivo.  In their lab, I studied ion and water transport across airway epithelium to delineate the mechanisms that regulate mucociliary clearance.   This gave me an understanding about many proteins in the airways that could be manipulated by drugs to increase mucociliary clearance and clear the blocked airways in obstructive pulmonary diseases like cystic fibrosis, COPD/chronic bronchitis, and asthma.  I have been fortunate to witness the dogma of the past that “mucus is there to protect you” be replaced over the past 15 years with an understanding of the importance of the airway epithelium and clearing mucus from diseased lungs. 

Q: What does the general landscape of this research area currently look like?

Recently the importance of airway hydration has been validated by FDA approval of mucoregulator drugs like Ivacaftor for people with cystic fibrosis that have class III gating mutations and has led to clinical trials of other mucoregulator and anti-inflammatory drugs I have worked on for COPD and asthma.  It is exciting to watch the drugs your team has invented move into clinical trials and help patients.

Q: What are the real-world implications of your research?

I have been fortunate to work on the teams that brought the drugs Dulera and Tezspire to the market.  These drugs are currently helping asthma patients live longer and more productive lives.

Q: How long have you been a SCIREQ user?

I have been using the flexiVent for over 20 years.  My first poster containing data from the flexiVent was presented at the 2005 American Thoracic Society meeting.

Phillips, J., Case, N., Chapman, R., Hey, J., and Minnicozzi, M.:  Pharmacological Characterization of Work of Breathing and Pulmonary Inflammation Reduction in an Allergic Guinea Pig Model of Asthma. Proc. Am. Thorac. Soc. 2:A487, 2005.

Q: How has using SCIREQ equipment helped with improving the translatability and reproducibility of your research?

Animal models of human disease have obtained a bad rap in the last 15 years due to poor prediction of translation of drug efficacy in clinical trials.  The assessment of lung function endpoints used in preclinical drug testing may hold the key to translation of drug efficacy from mouse to man. Improvement in lung function as measured by the Forced Expiratory Volume exhaled in 1 second (FEV1) is commonly a primary endpoint in clinical trials to determine the efficacy of novel drugs for respiratory diseases. In preclinical models, when developing drugs other than bronchodilators, improvements in lung function require higher doses or multiple days of dosing compared to drug doses required to decrease other preclinical model endpoints like inflammatory cells in bronchoalveolar lavage or airway hyperreactivity to methacholine.  This suggests that lung function endpoints set a higher bar for efficacy and should also be primary preclinical endpoints.

Stevenson, C., S. Sridhar, and J.E. Phillips. 2013, Predicting Drug Efficacy using Integrative Models for Chronic Respiratory Diseases. Inflamm. Allergy Drug Targets, 12:124-131.

Q: What were some insights that the flexiVent/inExpose helped you obtain?

Functional changes in baseline lung mechanics as measured by flexiVent represent a higher bar for detecting drug efficacy than pulmonary inflammation measurements (BronchoAlveolar Lavage fluid eosinophils) or Airway HyperReactivity to methacholine.  Corticosteroid induced improvement in lung function measurements required higher doses or multiple days of dosing compared to the dose required to decrease BAL cell counts or AHR. 

Q: What advice do you have for someone starting out in this research area?

Always budget some of your time to continue to research questions that arise from your past research and to write manuscripts.  Follow the rule of the 5 P’s: Proper Preparation Prevents Poor Performance

Q: What’s next for your lab and your research?

Many genes are linked to the development of COPD by genome wide association studies.  These genes identified by GWAS might represent good drug targets and most are associated with the emphysema phenotype.  My lab is currently developing the elastase induced mouse model of emphysema to understand its utility in drug discovery.

Phillips, J., Wilson, K., Gomez, A., Zhang, X.: No Lung Regeneration Detected for Up to 1 Year After Single Elastase Challenge Is Used to Induce Emphysema in Mice. Am. J. Respir. Crit. Care Med. 205:A4673, 2022

Thank you Dr. Phillips for taking the time to do this interview!
 
Dr. Phillips recent publications:

Phillips, J.E., R. Peng, L. Burns, P. Harris, R Garrido, G.Tyagi, J.S. Fine, and C.S. Stevenson. 2012, Bleomycin Induced Lung Fibrosis Increases Work of Breathing in the Mouse. Pulm. Pharmacol. Ther., 25:281-285.

Phillips, J.E., R. Peng, P. Harris, L. Burns, L. Renteria, L.K.A. Lundblad, J.S. Fine, C. Bauer, and C.S. Stevenson. 2013, House Dust Mite Models: Will They Translate Clinically as a Superior Model of Asthma? J. Allergy Clin. Immunol., 132:242-244.

Harris, P., S. Sridhar, R. Peng, J.E. Phillips, R.G. Cohn, L. Burns, J. Woods, M. Ramanujam, M. Loubeau, G. Tyagi, J. Allard, M. Burczynski, P. Ravindran, D. Cheng, H. Bitter, J.S. Fine, C.M.T. Bauer, and C.S. Stevenson.  2013, Double-Stranded RNA Induces Molecular and Inflammatory Signatures that are Directly Relevant to COPD. Mucosal Immunol., 6:474-484. 

Peng, R., S. Sridhar, G. Tyagi, J.E. Phillips, R. Garrido, P. Harris, L. Burns, L. Renteria, J. Woods, L. Chen, J. Allard, P. Ravindran, H. Bitter, Z. Liang, C.M. Hogaboam, C. Kitson, D.C. Budd, J.S. Fine, C. Bauer, and C.S. Stevenson. 2013, Bleomycin Induces Molecular Changes Directly Relevant to Idiopathic Pulmonary Fibrosis: A Model for “Active” Disease. PLoS ONE, 8:e59348.

Li, S., M. Aliyeva, N. Daphtary, R.A. Martin, M.E. Poynter, S. Kostin, J. Van der Velden, A.M. Hyman, C.S. Stevenson, J.E. Phillips, L.K.A. Lundblad. 2014, Antigen Induced Mast Cell Expansion and Bronchoconstriction in a Mouse Model of Asthma. Am. J. Physiol. Lung Cell. Mol. Physiol., 306:L196-L206

Phillips, J.E., L. Renteria, L. Burnes, P. Harris, R. Peng, C. Bauer, D. Laine, and C.S. Stevenson. 2016, Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma. J. Aerosol. Med. Pulm. Drug. Deliv., 29:233-241.

Phillips, J.E., X. Zhang, and J.A. Johnston. 2017, Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice using a Nose-Only Exposure System, J. Vis. Exp., 122, e55454.

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