Dr. Chinoy established the Lung Development Research Program in 1995 in collaboration with Dr. Robert E. Cilley, M.D., a Pediatric Surgeon in the department of Surgery. We have two major projects under this program.

1) Pulmonary Hypoplasia : Gene Expression in Abnormal Lungs.

The goal of the members of the lung development research is to address a common birth defect found in human newborns- pulmonary hypoplasia (PH) and congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia occurs in 11 to 14 newborns in 10,000 live births, of which about 1 in 2,500 have associated congenital diaphragmatic hernia (CDH). Newborns with PH and CDH suffer from persistent pulmonary hypertension (PPH) and respiratory insufficiency or distress. Despite the availability of the surgical tools and other modern therapeutic treatments, this defect often results in death of these babies with abnormal lungs. The rate of mortality is about 50%.

The exact mechanisms or cause of these defects remain unknown. What is the trigger for disturbing the normal development of lungs in human babies before birth? Is the trigger hormonal or is it caused by some environmental toxins? Which genes may be involved in the formation of abnormal / insufficient lungs?

It is known that the herbicides and other teratogens, which are present in the environment, may cause certain defects in humans, especially when exposed during very early stages of pregnancy. We have, therefore, established a mouse model of pulmonary hypoplasia and congenital diaphragmatic hernia, which mimics the human condition, by using a herbicide - nitrofen. Our hypothesis is that the human embryo is exposed to a teratogen / herbicide at a very critical time during pregnancy. This results in abnormal development (malformation) of lung and heart, resulting in respiratory distress, which affects the survival of the babies born with this defect.

Our work is focused on identifying the genes responsible for this abnormal lung development and also on developing further understanding of the mechanisms involved in the defective embryonic development of heart, lung and blood vessel formation in lungs. More detailed work in this area will open avenues to help treat defects in unborn babies and in the long run prevent the fatal outcome of this defect in newborn babies.

2) Role of Retinoic Acid in Lung Morphogenesis and Modulation of Alveolar Formation:

Lung is a complex organ. Its differentiation, growth, maturation and maintenance of its integrity remain to be fully understood. Our long-term objective is to define the direct or indirect signaling pathways of specific lung morphogenesis. This project focuses on the effects and interactions of a potent morphogen - all-trans-retinoic acid (RA). RA influences developmentally crucial transcription factors such as Hox genes (regulates morphogenesis) and also members of the CCAAT/ enhancer binding protein (important regulators of surfactant proteins). RA and dexamethasone (DEX) have antagonistic effects on regulation of several genes. Although, DEX is commonly used for treatment of bronchopulmonary dysplasia (BPD), RA may have a potential role in BPD treatment because RA has been suggested to induce alveolar formation. Our goal is to dissect the pathways by which RA induces alveolar formation and also to identify the genes that RA induces or inhibits at different stages in development and at birth when lung becomes an air-breathing organ. We believe that these studies will shed light on some of the fundamental mechanisms governing lung development and differentiation.