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United States Department of Agriculture

Agricultural Research Service

LIPING HUANG

Research Geneticist

 

 

 

Ph.D., Department of Microbiology

University of Iowa

 

M.D., Shanghai Medical University

PR China

 

Office:     430 West Health Sciences Dr.

                 University of California

                 Davis, CA 95616

             

Phone:     (530) 754-5756 (office)

                 (530) 754-5757 (lab)

 

Fax:         (530) 752-5271

 

Huang Lab

                                                                                            

 

                                                                               

 

Biography

Dr. Liping Huang is a Research Geneticist at the USDA Western Human Nutrition Research Center and an Associate Adjunct Professor in the Department of Nutrition at the University of California, Davis. Dr. Huang obtained her M.D. degree in Medicine and Public Health at Shanghai Medical University in China. After working in the Shanghai Municipal Center for Disease Control and Prevention focusing on infectious diseases for several years, she studied in the Department of Microbiology, University of Iowa College of Medicine, where she earned her Ph.D. in molecular virology under Dr. Mark F. Stinski. 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 associate 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 made her a pioneer in mammalian zinc transporter research. Since joining the WHNRC, Dr. Huang has functionally characterized three novel zinc transporters that are important for regulation and maintenance of physiological zinc levels in the body and for dietary zinc absorption. Dr. Huang is a member of the Society for Zinc Biology and the American Society for Biochemistry and Molecular Biology.

Research Program

Dr. Huang has primarily focused on mammalian zinc transporter proteins and their roles in maintaining body zinc homeostasis, regulating body adiposity, and modifying insulin expression. She is also interested in the molecular mechanisms by which zinc and lunasin reduce the risk of prostate cancer. Her work involves cell lines and mice to investigate the roles of zinc in reduction of prostate cancer risk and in regulation of body weight, body fat, and insulin resistance.  

Research Accomplishments

Identified and characterized molecules involved in cellular zinc homeostasis.  A long-term objective of Dr. Huang’s research is to understand the mechanism by which cellular zinc homeostasis is maintained in humans and mice at the molecular level in healthy and diseased conditions. 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 regarding identification and characterization of the mouse Znt7 gene. To address the physiological roles 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. A significant reduction in the body fat accumulation was found in Znt7 knockout mice. This knockout mouse model provides molecular evidence indicating that zinc regulates body weight gain through regulation of adiposity of the body.

Connections between zinc nutrition, homeostasis and body adiposity and diabetes remain largely unknown. During the study of the phenotypes of the Znt7 knockout mice, Dr. Huang discovered that these mice are prone to development of insulin resistance and impaired glucose tolerance leading to diabetes. Over-expression of ZnT7 in pancreatic beta-cells (cells that produce the blood glucose-regulating hormone, insulin) increased insulin expression leading to higher insulin protein synthesis and basal insulin secretion.  It was a novel discovery that the insulin genes (Ins1 and Ins2) in rodents are the target genes of the metal-responsive transcription factor Mtf1. The studies establish the importance of cellular zinc in regulation of insulin synthesis and secretion and thus control of blood sugar level. The results have important implications for future research into mechanisms by which cellular zinc regulates insulin and glucose metabolism, and highlights that proper zinc nutrition and beta-cell zinc handling could be important for maintenance of metabolic health and blood sugar control.

Prostate cancer initiation occurs several decades before a slow progression gives rise to clinical cancer. Based on the results from a study (conducted in Dr. Huang’s laboratory) of cellular zinc homeostasis in tumorigenic and non-tumorigenic prostate epithelial cells, Dr. Huang hypothesized that a reduction in cellular zinc accumulation in the prostate was an important factor in driving the progression of prostate cancer. Therefore, Dr. Huang initiated a study 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). The results from this study demonstrated that TRAMP mice with a Znt7-null genetic background developed prostate cancer earlier than the wild type controls.

Selected Articles

 

1.    Tepaamorndech S, Huang L, Kirschke CP. A null-mutation in the Znt7 gene accelerated prostate tumor formation in a transgenic adeno-carcinoma mouse prostate model. Cancer Lett. 308:33-42, 2011.

 

2.    Galvez AF, Huang L, Magbanua MJ, Dawson K, Rodriguez RL. Lunasin peptide upregulates thrombospondin 1 (THBS1) gene expression in non-tumorigenic prostate epithelial cells. Nutrition and Cancer, 63:623-36, 2010.

 

3.    Huang, L, Yan M, Kirschke CP. Over-expression of ZnT7 increases insulin synthesis and secretion in pancreatic -cells by promoting insulin gene transcription. Exp. Cell Res. 316:2630-43, 2010.

 

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

 

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

 

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

 

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

 

8.    Magbanua MM, Dawson K, Huang L, Malyj W, Gregg J, Galvez A, Rodriguez RL. Nutrient-Gene Interactions Involving Soy Peptide and Chemopreventive Genes in Prostate Epithelial Cells. In:  “Nutritional Genomics: Discovering the Path to Personalized Nutrition”, A Kaput and Rodriguez  eds, John Wiley & Sons, Inc., 2006.

 

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

 

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

 

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

 

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

 

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

 

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

 

15.  Huang L, Kuo YM, Gitschier J. The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency. Nat. Genet. 23:329-332,1999.

 

16.  Huang L, Gitschier J. A novel gene involved in zinc transport is deficient in the lethal milk mouse.  Nat. Genet. 17:292-297, 1997.

 

 

 

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Last Modified: 1/27/2012
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