The major interest of my lab is to understand the transcriptional regulatory mechanisms involved in human diseases with a focus on cardiovascular diseases and cancer. We use a multidisciplinary approach, including molecular and cellular biology, genetics, biochemistry, immunology, and electrophysiology. There are four on-going projects in the lab that focus on the transcription factor Forkhead box protein O4 (FoxO4), leucine zipper transcription factor like-1 (LZTFL1), and the epigenetic regulator JMJD2A, a member of the jumonji-C family of histone lysine demethylases (KDMs).
We established several mouse models of human diseases in the lab, including carotid artery ligation as a model of human restenosis, an inflammatory bowel disease model, and mouse models of ischemic diseases and cardiac hypertrophy. We have studied the biology of both FoxO4 and JMJD2A in the context of these models.
Project 1: Transcriptional mechanisms of ischemic diseases.
The mammalian forkhead transcription factor O sub-family consists of FoxO1, FoxO3, FoxO4, and FoxO6. FoxO proteins are involved in a variety of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. While a majority of studies in the field have investigated FoxO1 and FoxO3, my lab has focused on FoxO4. We have made several key contributions to the field. Read more.
Project 2. Epigenetic regulation of cardiac hypertrophy and heart failure.
Epigenetic control via chromatin modification is recognized as a fundamental mechanism for regulating gene expression throughout development and in diseases. However, the role of histone methylation in cardiac biology remains largely unexplored. The fetal gene program is silenced in adult hearts and reactivated during pathological hypertrophic remodeling. Trimethylation of histone 3 lysine 9 (H3K9me3) is a conserved histone modification normally associated with transcriptionally silent chromatins. Removal of H3K9me3 may de-repress transcription. Read more.
Project 3: Tumor suppressive functions of LZTFL1.
Human LZTFL1 is located in the chromosome region 3p21.3, a hotspot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens. Read more.
Project 4: Small molecule inhibitors of histone demethylases in prostate cancer.
The standard androgen deprivation therapies involving either chemical or surgical castration for androgen-dependent prostate cancer (ADPC), although effective at the beginning, can lead to inevitable castration-resistant prostate cancer (CPRC), which is lethal to patients. The growth of both ADPC and CRPC depends on androgen receptor (AR)-signaling. Read more.