Boston University Medical Campus
Pulmonary, Critical Care, and Allergy Medicine

Medical School:

Special Interests
RESEARCH:

• Stem Cells
• Injury Repair
• Lung Regeneration
• Lung-Hematopoietic Stem/Progenitor Cell Interactions

CLINICAL: General Pulmonary MedicineDr 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 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 extent and mechanisms involved in adult lung regeneration.

The Fine laboratory is addressing these broad themes in a variety of experimental contexts, including mouse lung development and adult lung injury repair.  Using these model systems, they seek to identify reparative and progenitor cell lung populations, and the genetic programs that control their fate.  One particular interest involves understanding how differentiated mesenchymal elements, such as bronchial and pulmonary artery vascular smooth muscle evolve and differentiate during embryogenesis.  Clarification of these issues has broad implications for understanding the basic biology of the lung and also for the design of therapies for a variety of lung diseases, including asthma, pulmonary hypertension, and interstitial pulmonary fibrosis.

An extension of these studies involves defining the interactions between the developing lung and the developing hematopoietic system. These interactions are necessary for establishing a local and functional innate immune system prior to birth. This work is focused on elucidating how the embryonic lung locally controls differentiation of myeloid progenitors that the Fine lab found localized to the primitive fetal lung mesenchyme. They are also pursuing studies that will determine how certain distinct classes of hematopoietic cells regulate development of the lung’s arterial system in utero.

Representative Publications:

1. Fine, A. Breathing Life into the Lung Stem Cell Field. Cell Stem Cell 4:468-469, 2009.
2. Murphy, J., Summer, R., Wilson , A.A., Kotton, D.N., and Fine, A. The Prolonged Life-Span of Alveolar Macrophages. American. Journal Respiratory. Cell Molecular Biology 38 : 380-385, 2008.
3. Summer, R., Fitzsimmons K., Murphy, J, and Fine, A. Isolation and Characterization of an Adult Lung Mesenchymal Progenitor Cell.  Am J Respir Cell Mol Biol. 37:152-9, 2007.
4. Kotton, D.N., Ma, B.Y., Cardoso, W.V., Sanderson, E.A., Summer, R.S., Williams, Mary C . and Fine, A. Bone Marrow Cells as Progenitors of the Lung Alveolar Epithelium. Development, 128:5181-5188, 2001.

Links:

• Stem Cell Biology Group