NYMC > Faculty > Directory > By Name > Xu, Dazhong

Dazhong Xu, Ph.D.

Associate Professor of Pathology
Vice Chair of Research

Email:

dazhong_xu@nymc.edu

Address:

Department of Pathology
Basic Sciences Building
New York Medical College
Valhalla, NY 10595

Professional Interests:

The research interest of my laboratory is in molecular and cellular biology of cancer. We work to elucidate molecular mechanisms underlying carcinogenesis and cancer progression with a focus on lung cancer. The lab employs state-of-the-art molecular, cellular, and genetic tools as well as mouse models to achieve our research goals. The two main research projects in the lab are the following:  

1. Genomic instability and lung carcinogenesis

Genomic instability is a well-established hallmark of cancer and a major contributor of carcinogenesis and cancer progression. Although many cellular activities are involved in this process, perturbation of the cellular DNA damage and repair mechanism is one of the major reasons for genomic instability to occur. We recently discovered that Gene 33 (also named Mig6 and ERRFI1), an adaptor/scaffold protein previously known to only have cytoplasmic functions, is also located in the nucleus and associated with chromatin. Our data indicate that nuclear/chromatin Gene 33 may regulate the DNA damage response and DNA repair in response to genotoxic stress. This mechanism likely contributes to lung carcinogenesis induced by genotoxic carcinogens, such as hexavalent chromium. The goal of this research project is to understand the mechanism underlying the regulation of DNA damage/repair by Gene 33 and whether this newly identified biological process contribute to lung carcinogenesis.

2. The hypoxic response and lung cancer

Adaptation to the hypoxic condition is critical for cancer cells, as these cells are often subjected to hypoxia due to rapid growth of solid tumors. The ability of cancer cells to survive in the hypoxic condition develops over time through remodeling of key cellular processes such as energy metabolism, angiogenesis, and cell survival. These processes involve both cancer cells and the microenvironment surrounding them, i.e. tumor microenvironment. The HIF transcription factors play central roles in both acute and chronic cellular responses to hypoxia. These factors, particularly HIF-1, are the main regulators of adaptation of cancer cells to hypoxia. The alpha subunit of the HIF-1 transcription factor (HIF-1α), which exists at a very low level under normoxia due to constant proteasome-dependent degradation, is stabilized by hypoxia. The increase in the level of the HIF-1α protein serves as the primary mechanism for HIF-1 activation. Expression of HIF-1α is often high in cancer cells as a result of adaptation to hypoxia. The stability or subcellular localization of HIF-1α can also be regulated by its phosphorylation by protein kinases, such as polo-like kinase 3 (Plk3). We recently discovered that Plk3 is subjected to degradation by the ubiquitin-proteasome system. We found that SIAH2, a hypoxia-inducible ubiquitin E3 ligase, mediates Plk3 ubiquitination and degradation by the proteasome. Interestingly, we found that Plk3 also phosphorylates and promotes degradation of SIAH2. Given the known role of SIAH2 in stabilizing HIF-1α, the mutual regulative mechanism between Plk3 and SIAH2 functions to fine-tune the level of HIF-1α. We believe that this signaling pathway plays a significant role in the adaptation of cancer cells to hypoxia, thereby regulating cancer progression. The goal of this research project is to gain comprehensive understanding of the mechanism of this novel signaling pathway, the contribution of this pathway to lung carcinogenesis and cancer progression, and the potential of this pathway as a therapeutic target.

Education Profile:

Post Graduate Studies:   Massachusetts General Hospital/Harvard Medical School, Tufts Medical Center

Graduate Degree:  M.S., Ph.D.

Graduate Degree Institution:   University of Florida, Wright State University

Undergraduate Institution:   Nanjing University

 

Selected Bibliography:

Search PubMed for all available publications of Dazhong Xu, Ph.D.