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

MD, University of Michigan



Research interests include:

-Stem Cells
-Injury Repair
-Lung Development and Regeneration
-Mesothelium

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, Division of Graduate Medical Sciences


Boston Medical Center




The Fetal Lung Mesothelial Differentiation Program
06/01/2016 - 05/31/2018 (PI)
NIH/National Heart, Lung, and Blood Inst
4R01HL116163-04

Development of PNEC innervations and neuroplasticity after early life insult
05/01/2017 - 04/30/2018 (PI)
The Brigham and Women's Hospital, Inc. NIH NHLBI
1R01HL132991-01A1

The Fetal Lung Mesothelial Differentiation Program
08/05/2013 - 05/31/2017 (PI)
NIH/National Heart, Lung, and Blood Inst
5R01HL116163-03

Identifying the Molecular Phenotype of Normal and Asthmatic Bronchial Smooth Muscle
01/01/2012 - 12/31/2015 (PI)
NIH/National Heart, Lung, and Blood Inst
5R21HL112619-02

NEW APPROACHES FOR THE STUDY OF LUNG FIBROCYTES
12/01/2010 - 11/30/2014 (PI)
NIH/National Heart, Lung, and Blood Inst
5R21HL106912-02

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

Bone Marrow Cells as Precursors of Alveolar Epithelium
07/01/2002 - 06/30/2007 (PI)
NIH/National Heart, Lung, and Blood Institute
5 R01 HL69148 04

Enhancing Marrow Cell Replacement of Injured Lung Tissue
09/11/2002 - 07/31/2006 (PI)
NIH/National Heart, Lung, and Blood Institute
5 R21 HL72205 03

Showing 10 of 13 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
2016 The Fetal Lung Mesothelial Differentiation Program 4R01HL116163-04 3
2014 The Fetal Lung Mesothelial Differentiation Program 5R01HL116163-02 3
2013 The Fetal Lung Mesothelial Differentiation Program 1R01HL116163-01A1 3
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
2012 Microscopy-Image Analysis and FACS Core 5P01HL047049-20-5547 86
2011 Microscopy-Image Analysis and FACS Core 5P01HL047049-19-5547 86
2011 Microscopy-Image Analysis and FACS Core 5P01HL047049-19-5547 86
2011 New Approaches for the Study of Lung Fibrocytes 1R21HL106912-01
Showing 10 of 49 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. 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.
  2. 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;.
  3. 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;.
  4. 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;.
  5. 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;.
  6. 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;.
  7. 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.
  8. Paez-Cortez J, Krishnan R, Arno A, Aven L, Ram-Mohan S, Patel KR, Lu J, King OD, Ai X, Fine A. A new approach for the study of lung smooth muscle phenotypes and its application in a murine model of allergic airway inflammation. PLoS One. 2013; 8(9):e74469.View Related Profiles. PMID: 24040256; PMCID: PMC3767675; DOI: 10.1371/journal.pone.0074469;.
  9. Braubach OR, Miyasaka N, Koide T, Yoshihara Y, Croll RP, Fine A. Experience-dependent versus experience-independent postembryonic development of distinct groups of zebrafish olfactory glomeruli. J Neurosci. 2013 Apr 17; 33(16):6905-16. PMID: 23595749; DOI: 10.1523/JNEUROSCI.5185-12.2013;.
  10. Ohle SJ, Anandaiah A, Fabian AJ, Fine A, Kotton DN. Maintenance and repair of the lung endothelium does not involve contributions from marrow-derived endothelial precursor cells. Am J Respir Cell Mol Biol. 2012 Jul; 47(1):11-9.View Related Profiles. PMID: 22323363; PMCID: PMC3402798; DOI: 10.1165/rcmb.2011-0180OC;.
Showing 10 of 70 results. Show More

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

Bar chart showing 70 publications over 28 distinct years, with a maximum of 6 publications in 2005

YearPublications
19871
19892
19902
19912
19921
19933
19943
19952
19962
19972
19984
19992
20004
20011
20021
20034
20045
20056
20072
20084
20093
20101
20113
20121
20134
20143
20161
20171
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

mesenchyme
smooth muscle development
stem cells
Vessels
Contact for Mentoring:


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