Current Projects

The Cornfield Lab work's across disciplines to expand the frontiers of scientific understanding while moving the most promising breakthroughs into tangible health benefits.

Hypoxia Inducible Factor-1α(HIF-1α) in Bronchopulmonary Dysplasia

In our lab, he has focused on the role of cell specific expression of HIF-1α in neonatal hyperoxia-inducible lung injury, called Bronchopulmonary Dysplasia (BPD). In lung development, alveolarization is made from the division of alveolar ducts into alveolar sacs by secondary septation due to angiogenesis driven by Vascular-endothelial growth factor (VEGF). However, preterm delivered infants with immature lung development, especially less than 28 weeks gestational age, must receive the respiratory support to rescue the respiratory failure with manualized ventilation and oxygen supplementation. These therapies cause arrested lung development with impaired alveolarization, interrupted angiogenesis and fibrosis. Although the therapy about prematurity of lung is to use lung protective strategy with using less oxygen and higher-pressure ventilation, 85% of infants born less than 700 g are diagnosed with, and suffer from BPD. Once with BPD, their lung function continues to deteriorate until adulthood leading to obstructive lung disease. Moreover, 16~25% of them suffer from pulmonary hypertension (PH), and show higher mortality with up to 48% per 2 years after diagnosed with PH.

Although some literature demonstrates that the alveolarization in animal models is improved by promoting angiogenesis driven with VEGF, HIF-1α and so on, whether the cell specific expression of HIF-1α protein modulates lung development remains unknown.

Reiji has been studying the effects in lung development using a cell specific expression of HIF-1α in an animal model using a variety of approaches including; cell biology, biochemistry, and physical function tests.

Lung PAEC Barrier Function

Compromised pulmonary endothelial cell (PEC) barrier function characterizes acute respiratory distress syndrome (ARDS), a cause of substantial morbidity and mortality. Survival from ARDS is greater in children compared with adults. Whether developmental differences intrinsic to PEC barrier function contribute to this survival advantage remains unknown. To test the hypothesis that PEC barrier function is more well-preserved in neonatal lungs compared with adult lungs in response to inflammation, we induced lung injury in neonatal and adult mice with systemic lipopolysaccharide (LPS). We assessed PEC barrier function in vivo and in vitro, evaluated changes in the expression of focal adhesion kinase 1 (FAK1) and phosphorylation in response to LPS, and determined the effect of FAK silencing and overexpression on PEC barrier function. We found that LPS induced a greater increase in lung permeability and PEC barrier disruption in the adult mice, despite similar degrees of inflammation and apoptosis. Although baseline expression was similar, LPS increased FAK1 expression in neonatal PEC but increased FAK1 phosphorylation and decreased FAK1 expression in adult PEC. Pharmacologic inhibition of FAK1 accentuated LPS-induced barrier disruption most in adult PEC. Finally, in response to LPS, FAK silencing markedly impaired neonatal PEC barrier function, whereas FAK overexpression preserved adult PEC barrier function. Thus, developmental differences in FAK expression during inflammatory injury serve to preserve neonatal pulmonary endothelial barrier function compared with that of adults and suggest that intrinsic differences in the immature versus pulmonary endothelium, especially relative to FAK1 phosphorylation, may contribute to the improved outcomes of children with ARDS.

Single cell RNAseq

Single cell RNAseq project is to define the heterogeneity of murine pulmonary cell types, their distinct subpopulations and dynamic changes in gene expression, and to understand the adaptive switches at the different lung developing. We combined single cell sorting and RNA sequencing approaches to identify distinct populations of endothelial, mesenchymal, and immune cells, and distinct subpopulations. This project is undertaking in collaboration with the Dr. Quake and Dr. Alvira labs at Stanford.


Approximately 15 million babies are born preterm each year, and about one million of those babies will die because of it. In the United States, the premature birth rate has risen for the past 3 consecutive years, reaching an abysmal percentage of 9.93% of all births for 2017. Currently, there are no treatments available for a woman undergoing preterm birth, which is defined by the World Health Organization as gestation less than 37 weeks. This project investigates the cellular processes necessary for the initiation of labor prior to term and preterm birth. With a more concrete understanding of the physiological processes of labor, our laboratory hopes to develop anti-contractile or tocolytic therapies for the treatment and prevention of preterm birth.

The transient receptor potential vanilloid 4 (TRPV4) channel is a non-selective calcium permeable cation channel, which is activated by stimuli such as stretch temperature and swelling. Our laboratory has recently demonstrated that TRPV4 in the pregnant uterus functions to modulate myometrial contractility. Specifically, in studies with pharmacological blockade of TRPV4 we show that loss of the channel 1) diminishes cytosolic calcium entry into uterine smooth muscle cells, 2) decreases oxytocin-induced myometrial contraction, and 3) prolongs gestation in two distinct mouse models of preterm labor.  In contrast, increased TRPV4 activity in the pregnant uterus across gestation enhanced the susceptibility of mice to inflammation-induced preterm labor. Interestingly, TRPV4 is upregulated in the uterus during mid-gestation, well before the onset of labor. Expression patterns of TRPV4 thus suggest that the channel may additionally contribute to labor through the remodeling of the uterus from a non-contractile to a contractile tissue. Our two ongoing projects are thus aimed to deepen our understanding of how TRPV4 1) is regulated in the pregnant uterus across gestation and 2) modulates uterine inflammation and the molecular processes that lead to the onset of contraction, both in the context of term and preterm labor.

Recent studies demonstrate that micro RNAs regulate the expression of multiple contractile-associated genes within the cervix, myometrium, and placenta during pregnancy. In multiple tissues outside of the uterus, such as chondrocytes, the micro RNA 203 (miR-203) has been demonstrated to regulate TRPV4 expression via targeted degradation of TRPV4 RNA transcripts. In uterine tissue from pregnant mice, we show that miRNA-203 decreases concomitantly to increases in TRPV4 expression across gestation. Further, overexpression of miR-203 using a miR-203 mimic, suppresses TRPV4 expression in mouse uterine smooth muscle cells and diminishes myocyte contractility. We are now in the processes of developing miR-203 knockout mice to use as a direct tool to validate the function of miR-203 in the regulation of myometrial TRPV4 during pregnancy in murine models of term and preterm labor.

Inflammation is the only known pathology with substantial evidence of causality for both spontaneous term and preterm labor. Specifically, inflammation is observed as 1) innate and adaptive immune cells infiltrating the myometrium and the cervix, 2) upregulation of pro-inflammatory cytokines and chemokines in the amniotic fluid, myometrium and cervix, and 3) activation of the multifactorial transcription factor nuclear factor kappa B (NFkB) in the upper and lower uterine segment prior to the onset of labor. In tissues such as adipose and lung epithelial cells, TRPV4 has been demonstrated to promote inflammatory signaling through the activation NFkB and upregulation of multiple pro-inflammatory cytokines. Working in vitro with human uterine smooth muscle cells and primary mouse uterine smooth muscle cells, and in vivo with multiple mouse models preterm labor we are now actively studying the role of myometrial TRPV4 in the promotion of inflammation. Particularly, we are examining the potential role and mechanisms of TRPV4-dependent activation of NFkB and propagation of pro-inflammatory mediators (e.g. IL-1b, IL-6, MCP-1, and COX-2), and accessing its affects on myometrial contractility.

Conclusively, we believe understanding the molecular frame-work in which TRPV4 is regulated in the pregnant uterus and how it contributes to inflammation prior to the onset of spontaneous term and preterm labor will serve as a powerful tool for the development of novel tocolytics, with the ultimate goal of eradicating preterm birth.