Alan Fine, MD
Boston University School of Medicine
Dept of Medicine
Pulmonary, Allergy, Sleep & Critical Care Medicine

MD, University of Michigan at Ann Arbor

Research interests include:

-Stem Cells
-Injury Repair
-Lung Development and Regeneration

Clinical interests include:

General Pulmonary Medicine. Dr Fine is a Professor in the Department of Medicine and attends on the general pulmonary consult service, medical intensive care unit and acute pulmonary care clinics at the Boston VA Medical Center. In addition, Dr. Fine leads an active research laboratory. He is an-NIH funded Principal Investigator and Director of the Stem Cell Biology Program at the Boston University Pulmonary Center. He is also the recipient of a Congressionally Directed Medical Research Program Award (CDMRP) that is focused on developing novel cell based treatments for acute lung injury.

Background and detailed interests:

Knowledge about the identity, localization, and biology of lung stem/progenitor cells has lagged behind what is known for other organ systems. This state-of-affairs is a direct result of a variety of technical issues such as a deficiency of informative markers that can be used to precisely characterize putative stem cell populations in the lung. Advancements in the field have also been limited by impediments imposed by the unique biology of the lung, including its marked cellular complexity and slow cell turnover. One additional fundamental limitation in our knowledge base is an uncertainty over the true extent of adult lung regeneration.

The Fine laboratory is addressing these broad themes in a variety of experimental contexts, including mouse lung development and in models of adult lung injury repair. Using these systems, we seek to identify reparative and progenitor cell lung populations, and the genetic programs that control their fate. One particular interest involves understanding the origin, expansion mechanisms, and differentiation pathways controlling bronchial and pulmonary artery vascular smooth muscle cells during embryogenesis and disease. One example of this work is our focus on the role of Notch3 signaling in regulating vascular smooth differentiation in the peri-natal period. Our data indicate that this signaling system controls key aspects of a mature vascular smooth muscle cell phenotype, including a capacity to respond to vasoactive agonists in post-natal life. For these studies, we developed a series of unique mice that enable the high fidelity and independent isolation of bronchial or vascular smooth muscle cells for analysis. We have also generated a series of cell specific genetic mutants to support this line of investigation. An important extension of this work is to understand how the phenotype of smooth muscle cell populations becomes altered in disease. One salient example is elucidating the molecular basis for bronchial hyper-reactivity in neo-natal and adult asthma. Clarification of these issues has broad implications for understanding the basic biology of the lung and also for the design of therapies for asthma, pulmonary hypertension, and interstitial pulmonary fibrosis.

Our new focus on lung mesothelium is another example of our interest in deciphering the origin and differentiation pathways controlling the lung’s mesenchymal elements. Using a variety of novel genetic mouse models along with embryonic lung cultures, the contribution of mesothelial cells to normal lung development is being investigated. The objective of this work is to determine the specific types of differentiated lung cells that arise from the mesothelium along with the key signals involved in these cell fate decisions. These studies address important questions regarding the role of these cells not only in development, but also in homeostasis and disease.

Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences

Boston Medical Center

Medical student summer research program in heart, lung and blood diseases
02/01/2019 - 01/31/2024 (PI)
NIH/National Heart, Lung, and Blood Institute

Origins and functional roles of Miwi2-positive multiciliated cells during inflammation
03/07/2018 - 02/28/2022 (Co-PI)
PI: Matthew R. Jones, PhD
NIH/National Heart, Lung, and Blood Institute

Development of PNEC innervations and neuroplasticity after early life insult
05/01/2017 - 04/30/2021 (PI)
The Brigham and Women's Hospital, Inc. NIH NHLBI

The Fetal Lung Mesothelial Differentiation Program
06/01/2016 - 05/31/2019 (PI)
NIH/National Heart, Lung, and Blood Institute

The Fetal Lung Mesothelial Differentiation Program
08/05/2013 - 05/31/2017 (PI)
NIH/National Heart, Lung, and Blood Institute

Identifying the Molecular Phenotype of Normal and Asthmatic Bronchial Smooth Muscle
01/01/2012 - 12/31/2015 (Multi-PI)
PI: Alan Fine, MD
NIH/National Heart, Lung, and Blood Institute

12/01/2010 - 11/30/2014 (PI)
NIH/National Heart, Lung, and Blood Institute

New Approaches for the Study of Lung Fibrocytes
12/01/2010 - 11/30/2012 (PI)
NIH/National Heart, Lung, and Blood Institute
1 R21 HL106912 01

Circulating Mesenchymal Precursors with Fibrogenic Potential in Asthma
07/01/2007 - 06/30/2009 (Co-PI)
PI: Jaime P. Murphy, MD
Charles H. Hood Foundation

Derivation of Lung Epithelium from Bone Marrow
02/04/2003 - 01/31/2008 (Dept Sponsor)
NIH/National Heart, Lung, and Blood Institute
5 K08 HL71640 05

Showing 10 of 15 results. Show All Results

Acute Lung Injury: Making the Injured Lung Perform Better and Rebuilding Healthy Lungs
07/01/2008 - 01/31/2014 (PI)
Department of Defense

Yr Title Project-Sub Proj Pubs
2019 Origins and functional roles of Miwi2-positive multiciliated cells during inflammation 5R01HL136725-02 1
2018 Origins and functional roles of Miwi2-positive multiciliated cells during inflammation 1R01HL136725-01A1 1
2016 The Fetal Lung Mesothelial Differentiation Program 4R01HL116163-04 10
2015 The Fetal Lung Mesothelial Differentiation Program 5R01HL116163-03 10
2014 The Fetal Lung Mesothelial Differentiation Program 5R01HL116163-02 10
2013 The Fetal Lung Mesothelial Differentiation Program 1R01HL116163-01A1 10
2013 Identifying Molecular Phenotype of Normal and Asthmatic Bronchial Smooth Muscle 5R21HL112619-02 4
2012 Identifying the Molecular Phenotype of Normal and Asthmatic Bronchial Smooth Musc 1R21HL112619-01 4
2012 New Approaches for the Study of Lung Fibrocytes 5R21HL106912-02
Showing 10 of 54 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Norman TA, Gower AC, Chen F, Fine A. Transcriptional landscape of pulmonary lymphatic endothelial cells during fetal gestation. PLoS One. 2019; 14(5):e0216795.View Related Profiles. PMID: 31083674.
  2. Chen F, Shao F, Hinds A, Yao S, Ram-Mohan S, Norman TA, Krishnan R, Fine A. Retinoic acid signaling is essential for airway smooth muscle homeostasis. JCI Insight. 2018 Aug 23; 3(16).View Related Profiles. PMID: 30135301.
  3. Wasserman GA, Szymaniak AD, Hinds AC, Yamamoto K, Kamata H, Smith NM, Hilliard KL, Carrieri C, Labadorf AT, Quinton LJ, Ai X, Varelas X, Chen F, Mizgerd JP, Fine A, O'Carroll D, Jones MR. Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells. J Clin Invest. 2017 Oct 02; 127(10):3866-3876.View Related Profiles. PMID: 28920925.
  4. Chen F, Fine A. Stem Cells in Lung Injury and Repair. Am J Pathol. 2016 Oct; 186(10):2544-50.View Related Profiles. PMID: 27524796; DOI: 10.1016/j.ajpath.2016.05.023;.
  5. Stawski L, Haines P, Fine A, Rudnicka L, Trojanowska M. MMP-12 deficiency attenuates angiotensin II-induced vascular injury, M2 macrophage accumulation, and skin and heart fibrosis. PLoS One. 2014; 9(10):e109763.View Related Profiles. PMID: 25302498; PMCID: PMC4193823; DOI: 10.1371/journal.pone.0109763;.
  6. Rosner SR, Ram-Mohan S, Paez-Cortez JR, Lavoie TL, Dowell ML, Yuan L, Ai X, Fine A, Aird WC, Solway J, Fredberg JJ, Krishnan R. Airway contractility in the precision-cut lung slice after cryopreservation. Am J Respir Cell Mol Biol. 2014 May; 50(5):876-81.View Related Profiles. PMID: 24313705; PMCID: PMC4068941; DOI: 10.1165/rcmb.2013-0166MA;.
  7. Fine A. How narrative-based approaches distort medical decision-making. Hastings Cent Rep. 2014 May-Jun; 44(3):6-7; discussion 7. PMID: 24821242.
  8. Chen F, Marquez H, Kim YK, Qian J, Shao F, Fine A, Cruikshank WW, Quadro L, Cardoso WV. Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J Clin Invest. 2014 Feb 3; 124(2):801-11.View Related Profiles. PMID: 24401276; PMCID: PMC3904614; DOI: 10.1172/JCI70291;.
  9. Aven L, Paez-Cortez J, Achey R, Krishnan R, Ram-Mohan S, Cruikshank WW, Fine A, Ai X. An NT4/TrkB-dependent increase in innervation links early-life allergen exposure to persistent airway hyperreactivity. FASEB J. 2014 Feb; 28(2):897-907.View Related Profiles. PMID: 24221086; PMCID: PMC3898648; DOI: 10.1096/fj.13-238212;.
  10. Dixit R, Ai X, Fine A. Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry. Development. 2013 Nov; 140(21):4398-406.View Related Profiles. PMID: 24130328.
Showing 10 of 74 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 74 publications over 30 distinct years, with a maximum of 6 publications in 2005

In addition to these self-described keywords below, a list of MeSH based concepts is available here.

smooth muscle development
stem cells
Contact for Mentoring:

72 E. Concord St Housman (R)
Boston MA 02118
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