Biography

Dr. Liping Huang is a Research Geneticist at the USDA Western Human Nutrition Research Center at the University of California, Davis. Dr. Huang obtained her M.D. degree at Shanghai Medical University in China. After working in the Department of Epidemiology focusing on infectious diseases in Shanghai Center for Disease Control for several years, she attended the Graduate Studies in Department of Microbiology, University of Iowa College of Medicine, Iowa, where she earned her Ph.D. in molecular virology in Dr. Mark F. Stinski laboratory. Her interest in human and mouse genetics led her to the Howard Hughes Medical Institute at the University of California San Francisco, where she was trained as a post-doctoral fellow in molecular genetics in Dr. Gitschier’s laboratory. During her post-doctoral training , Dr. Huang discovered two defective genes responsive for two mouse inherited diseases, lethal milk and pallid, by genetic mapping and positional cloning strategies. The discovery and functional characterization of the lethal milk gene make her one of the pioneer scientists in mammalian zinc transporter research.

Research Interests

Dr. Huang’s research focuses on investigation of the regulatory mechanisms of zinc homeostasis in humans and mice and the effects of disrupted zinc homeostasis on prostate cancer development, body weight regulation, and endocrinal tissue function.  Her work involves animal studies examining the role of zinc in prostate cancer initiation and progression and in body weight regulation in mice.  

Research Accomplishments

Identified and characterized molecules involved in cellular zinc homeostasis.  Zinc is an essential trace element required for the activities of many different enzymes and transcription factors. A long-term objective of Dr. Huang’s research is to understand the mechanism how the cellular zinc homeostasis is maintained in humans and mice at the molecular level in the healthy and diseased conditions. Significant progress has been made recently in the understanding of how zinc is taken up into the cell, distributed between the cellular compartments, and exported to the extracellular space. However, many fundamental questions are remained to be solved, such as how zinc is taken up and subsequently transport into the bloodstream in the small intestine, how zinc transporters get to the target organelles of the cell after synthesis, how zinc is stored in the cell, and how zinc is subsequently released to use.  Identifying the players (zinc transporters) is one of the first steps in trying to answer these questions.  Three novel zinc transporters have been functionally characterized in Dr. Huang’ laboratory at WHNRC. The results suggest that these zinc transporters play important roles in zinc absorption in the small intestine, in zinc efflux in mammary glands, and in regulation of zinc homeostasis when cells are zinc deficient.

Generated and phenotypically characterized a zinc transporter knockout mouse model. In 2003, Dr. Huang’s laboratory reported a study in identification and characterization of the mouse Znt7 gene. In that study, Dr. Huang demonstrated that Znt7 was localized in the Golgi apparatus and functioned to accumulate zinc in the Golgi apparatus. To address the role of Znt7 in maintaining cellular zinc homeostasis in the body, a Znt7 knockout mouse model was generated in Dr. Huang’s laboratory. The study demonstrates that mice lacking Znt7 are zinc deficient. As the result, Znt7 knockout mice show phenotypes of reduced food intake and poor growth, which are classic manifestations of zinc deficiency. However, Znt7 knockout mice do not show any sign of hair growth abnormality and dermatitis that are commonly seen in dietary zinc-deficient animals and humans. A significant reduction in the body fat accumulation (~50% less than wild type) was found in Znt7 knockout mice. In addition, feeding Znt7 knockout mice with a zinc supplemented diet cannot correct the growth retardation. The Znt7 knockout mice, for the first time, provide molecular evidence indicating that zinc regulates body weight gain through regulation of adiposity of the body and endocrinal tissue function.

The chance of getting prostate cancer goes up as a man gets older. Prostate cancer appears to be unique compared to other cancers. The precursor for prostate cancer, prostatic intra-epithelial neoplasia (PIN), is very common. PIN is present in about one-third of men between the ages of 30-39, and it is detected even more frequently with increased age. Since most prostate cancers are detected in men between the ages of 50 and 70, this indicates that prostate cancer initiation occurs several decades before a slow progression gives rise to clinical cancer. Based on the results from the study of cellular zinc homeostasis in tumorigenic and non-tumorigenic prostate epithelial cells in Dr. Huang laboratory, Dr. Huang hypothesized that a reduction in zinc accumulation in the prostate was a crucial factor in driving the progression of prostate cancer. Therefore, Dr. Huang initiated a study in 2007 to investigate the effect of a reduction of cellular zinc in prostate epithelium (due to the Znt7-null mutation) on the prostate cancer initiation and progression in TRAMP mice (the mouse model of human prostate cancer). TRAMP mice present PIN around 10 weeks old and develop prostate cancer around 24 weeks. The preliminary results from this study demonstrated that TRAMP mice with Znt7-null genetic background developed PIN earlier and severer than the wild type controls. Primary prostate cancer and local/distance metastasis are detected in 30-40% 16 weeks old TRAMP/Znt7-/- mice. None of 16 or 20 weeks old wild type TRAMP mice developed primary prostate cancer in this study. The study is continuing in Dr. Huang’s laboratory to identify the target genes that are affected by zinc.

The work is represented by the following publications:

Kirschke CP, Huang L. 2008. Expression of ZNT (SLC30) family members in the epithelium of the mouse prostate during sexual maturation. J. Mol. Histol. 39:359-370.

Huang L, Yu YY, Kirschke CP, Gertz ER, Lloyd KK. 2007. Znt7 (Slc30a7)-deficient mice display reduced body zinc status and body fat accumulation. J. Biol. Chem. 282:37053-37063.

Huang L, Kirschke CP. 2007. A di-leucine sorting signal in ZIP1 (SLC39A1) mediates endocytosis of the protein. FEBS J. 274:3986-3997.

Yu YY, Kirschke CP, Huang L. 2007.  Immunohistochemical analysis of ZnT1, 4, 5, 6, and 7 in the mouse gastrointestinal tract. J.Histochem. Cytochem. 55:223-234.

Huang L, Kirschke CP, Zhang Y. 2006. Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a possible role in prostate cancer progression. Cancer Cell Int. 31;6:10.

Huang L, Kirschke CP, Zhang Y, Yu YY. 2005. The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. J. Biol Chem. 280:15456-15463.

Andree KB, Kim J, Kirschke CP, Gregg JP, Paik H, Joung H, Woodhouse L, King JC,  Huang L. 2004 Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans. J Nutr. 134:1716-1723.

Palmiter RD, Huang L. 2004. Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflugers Arch. European J. Physiology. 447:744-751.

Kirschke CP, Huang L. 2003. ZnT7, a novel mammalian zinc transporter, accumulates zinc in the Golgi apparatus. J Biol Chem. 278:4096-102.

Huang L, Kirschke CP, Gitschier J. 2002. Functional characterization of a novel mammalian zinc transporter, ZnT6. J. Biol. Chem. 277:26389-95.