-Dr. Jinhua Wu

Dr. Jinhua Wu is a Postdoctoral Research Scientist at the Center for Radiological Research (CRR). She received her PhD from the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University where her thesis work focused on signaling crosstalk between the G-protein coupled receptor and transforming growth factor β pathways in breast and ovarian cancers. After she obtained her PhD, she became an associate professor at the Chinese Academy of Sciences, studying the role of radiation treatment in breast cancer cell dedifferentiation. In 2013, she joined the CRR and her current research is focused on interpreting the effects of environmental stressors, such as low dose radon exposure, in lung tissue carcinogenesis using the state-of-the-art accelerator based microbeam irradiator located at the Radiological Research Accelerator Facility (RARAF).

Evaluating the Function of Mitochondria During Cytoplasmic Irradiation
The United States Environmental Protection Agency (EPA) reports about 21,000 radon related lung cancer cases each year and recognizes it as the second leading cause of lung cancer in the United States. Radon is a radioactive decay product of uranium, is ubiquitous in indoor environments, and decays quickly with a half-life of 3.82 days emitting high linear energy transfer (LET) α-particles during the process. Using the RARAF precision microbeam irradiator with a beam width of 1 μm, Dr. Wu and colleagues were able to examine the emitted α-particles’ effects using in vitro cell models. By specifically irradiating subcellular targets using the microbeam, the selective role of both the cytoplasm and nucleus in responding to α-particle irradiation were examined. Currently, Dr. Wu is focusing on the biological functions of cytoplasm post irradiation and identifying key protein regulators for these biological functions.
Dr. Wu’s research has shown in response to mitochondrial stress caused by cytoplasmic irradiation, specific proteins are upregulated, including mitochondria fission protein dynamin-related protein-1 (DRP-1) which leads to increased mitochondria fission and dysfunction. Furthermore, the increased level of DRP-1 is also associated with mitophagy initiation, increasing frequency of whole cell autophagy.


Figure 1. cytoplasmic irradiation leads to increased mitophagy.

Autophagy is an intracellular degradation system that delivers cytoplasmic cellular components to the lysosome for controlled disassembly and recycling. While autophagy plays a wide variety of physiological and pathological roles, in the case of cytoplasmic irradiation, Dr. Wu verified mitochondrial dysfunction mediated autophagy protects irradiated lung epithelial cells from radiation induced cell death, and leads to increased genomic instability.

Identifying Key Protein Targets During Lung Tumorigenesis
Better understanding of cellular signaling pathways activated by cytoplasmic irradiation provides insightful information to prevent radon induced lung cancer. For this purpose, Dr. Wu performed a process known as RNA-seq to look for unique genes regulated by cytoplasmic irradiation and by comparing them to both control and nuclear-irradiated samples was able to identify specific protein targets including a kinase called Pim-1. Using knockdown assays, Pim-1 was then confirmed to regulate the increase of glycolysis in response to cytoplasmic irradiation. Glycolysis is the metabolic pathway that converts glucose into pyruvate and releases 2 molecules of ATP, which are used as energy by the cell. Cancer cells often exhibit hyperactive glycolysis, which provides a large supply of ATP as well as a primary route for carbon influx that is required for biosynthesis of essential macromolecules and formation of organelles during increased proliferation in tumorigenesis. Establishing the link of Pim-1 to glycolysis during lung cell tumorigenesis may provide an important potential target for radon induced cancers.



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