USCACA 2012 Awardee Summary

Dr. Xiuli Bi, College of Life Science, Liaoning University, Shenyang
Dr. Xiuli Bi, currently an Associate Professor at the College of Life Science, Liaoning University in Shenyang, China, received her B.S. degree in Pharmaceutical Science from Hebei Medical University in 2000 and a Ph.D. degree in Pharmacology from Shenyang Pharmaceutical University in 2005. In 2005, Dr. Bi did her first postdoctoral research on cancer biology at the University of Alabama at Birmingham, Birmingham, Alabama in USA. In 2007, Dr. Bi joined Dr. Wancai Yang’s laboratory at the University of Illinois at Chicago,Chicago, Illinios, USA, to pursue her studies on carcinogenesis and chemoprevention of colorectal cancer.

Colorectal cancer is a significant and common public health problem worldwide. In the United States, colorectal cancer is the second-leading cause of cancer-related deaths equally in both men and women. With life style changes in the recent years in China, the incidence of colorectal cancer and death rate among all the malignant diseases have increased to 10.6% and 7.8%, respectively. Thus, a better understanding of cellular and molecular mechanisms underlying the development and progression of colorectal cancer is crucial for identifying new targets for effective prevention and treatments.Dr. Bi and her colleague firstly found that genetic deficiency of decorin, a member of the small leucine-rich proteoglycan (SLRPs), causes intestinal tumor formation through disruption of intestinal cell maturation, which was associated with aberrant expression of beta-catenin and E-cadherin. This work was published in Carcinogenesis in 2008. Her recent work conducted in China further showed that decorin plays a critical role in controlling cancer cell migration via interaction with E-cadherin, which was recently published in Carcinogenesis (2012). She also used food intervention as a promising strategy for colorectal cancer prevention. Dr. Bi and her colleague found that freeze-dried black raspberries (BRB) could efficiently prevent intestinal tumorigenesis in Apc and Muc2 mouse models of colorectal cancer. This novel finding was published in Cancer Prevention Research in 2010 that received positive responses from the academic community and the public.
In October 2010, Dr. Bi returned to China and assumed a faculty position as an Associate Professor at the College of Life Science in Liaoning University. She has been continuing her studies on colorectal carcinogenesis, metastasis, prevention and treatment. She has successfully developed the cancer research program at Liaoning University and established various collaborations nationally and internationally. Her research has been supported by the National Science Foundation of China, Board of Education of Liaoning Province and a Start-up Fund from Liaoning University. Her studies that were performed in China have been recently published in high-impact journals including Carcinogenesis (2012), Journal of Agricultural and Food Chemistry (2012), and European Journal of Medicinal Chemistry (2012). Based on her achievements, Dr. Bi was selected for several prestigious awards including
Outstanding Young Talents of Liaoning Province and Outstanding Talents of Shenyang in 2011. Selected Publications: 1. Bi X, Pohl NM, Qian Z, Yang GR, Gou Y, Guzman G, Kajdacsy-Balla A, Iozzo RV,
Yang W. Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice. Carcinogenesis, 2012, 33 (2) 326-30.
2. Bi X, Pohl NM, Yin Z, Yang W. Loss of JNK2 Increases Intestinal Tumor Susceptibility in Apc1638+/- Mice with Dietary Modulation. Carcinogenesis, 2011, 32(4) 584-588.
3. Bi X, Fang W, Wang LS, Stoner G, Yang W. Chemoprevention of black raspberry in Apc and Muc2 models of human colorectal cancer. Cancer Prevention Research, 2010, 3(11); 1443–50.
4. Bi X, Tong C, Dockendorff A, Bancroft L, Gallagher L, Guzman G,Iozzo RV, Augenlicht LH, Yang W. Genetic Deficiency of Decorin Causes Intestinal Tumor Formation through Disruption of Intestinal Cell Maturation. Carcinogenesis, 2008, 29(7):1435-40.
Dr. Binghui Li, Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin
Dr. Binghui Li, currently a professor at Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, received his BS degree in Bioengineering from Nanchang University, Nanchang, Jiangxi, in 2000, and PhD degree in Biochemistry and Molecular Biology in Graduate University of Chinese Academy of Sciences, Beijing, in 2006, and was awarded with the President Scholarship of Chinese Academy of Sciences in 2006.
In 2007, Dr. Li joined Dr. Wei Du’s Laboratory at the Ben May
Department for Cancer Research, the University of Chicago, Chicago, USA. A major research project of Dr. Li was to study the interactions between retinoblastoma (Rb) tumor suppressor and tuberous sclerosis protein 2 (TSC2) in cancer cell models. Rb is frequently inactivated in human cancers. In Dr. Du’s laboratory, a genetic screen was carried out in Drosophila to identify mutations that are synthetic lethal with Rb mutant cells. Gig (fly version of TSC2) was identified and the inactivation of both rbf (fly version of Rb) and gig was found to synergistically induce cell death. Dr. Li showed that the inactivation of TSC2 specifically also kills Rb mutant cancer cells under stress conditions, which is correlated with an inhibition of tumor growth. Furthermore, cancer cell death induced by concomitant inactivation of Rb and TSC2 is mediated by increased cellular stress, including oxidative stress. Inactivation of TSC2 and Rb synergistically induced oxidative stress via increased protein synthesis, and inhibited de novo lipid synthesis, and decreased induction of the ROS scavenger enzyme SOD2. Although cancer cells often exhibit inactivation of
tumor suppressors such as Rb, this knowledge has yet to be exploited to develop targeted cancer therapies. These results suggest that TSC2 could be a target for specifically killing of Rb deficient cancer cells, which are frequently found in human cancers. This outstanding work was published in Cancer Cell in 2010, and subsequently highlighted at Science and Cancer Research.
In Dr. Du’s laboratory, Binghui also demonstrated that extract from American ginseng was able to induce apoptosis in colon cancer cells. Simultaneously, it increased reactive oxygen species (ROS) that activated the NF-kB signaling pathway and thus enhanced the survival of colon cancer cells. Therefore, antioxidants increased the cancer-killing ability of American ginseng extract. Its main bioactive components, ginsenosides, induced both apoptosis and paraptosis-like cell death in colon cancer cells by activating p53.
At present, Dr. Li leads a research group working on cancer metabolism and dissecting how the irreversible upsetting of metabolic homeostasis induces cancer cell death.
Selected Publications 1. TianW.,MaX.,ZhangS.,SunY.andLiB.FattyAcidSynthaseInhibitorsfrom
Plants and Their Potential Application in the prevention of Metabolic Syndrome.
Clin Oncol Cancer Res., 8: 1-9. (2011) 2. LiB.,ZhaoJ.,WangCZ,SearleJ.,HeTC.,YuanCS.,andDuW.Ginsenoside
Rh2 induce apoptosis and paraptosis-like cell death in colon cancer cells through
activation p53. Cancer Letters, 28;301(2):185-92. (2011) 3. LiB.,GordonGM.,DuCH.,XuJ,andDuW.SpecifickillingofRbmutantcancer
cells by inactivating TSC2. Cancer Cell, 17: 469-480. (2010) Highlighted in Science(2010;328:1455) and Cancer Research (2010;70:5198) ; Evaluated by“Faculty Of 1000 Biology”.
4. LiB.,wangCZ.,HeTC.,YuanCS.,andDuW.AntioxidantspotentiateAmerican ginseng-induced killing of colorectal cancer cells. Cancer Letters, 289 (1), 62-70. (2010).
Dr. Lina Zhang, Department of breast cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
Dr. Lina Zhang, currently an attending doctor in the Department of breast cancer at the Tianjin Medical University Cancer Institute & Hospital, received her BS degree in Clinical Medicine in 2002, her MS degree in Oncology in 2008, and her PhD degree in Epidemiology and Health Statistics in 2011 from the Tianjin Medical University. Subsequently, Dr. Zhang joined the faculty of Tianjin Medical University Cancer Institute & Hospital, where she works as a breast cancer surgeon and a cancer researcher.
In 2010, Dr. Lina Zhang joined Dr. Wei Zhang’s laboratory in the Department of Pathology at the M.D. Anderson Cancer Center,
University of Texas, Houston, Texas, USA as a Global Academic Programs Associate and an exchange PhD student from the laboratory of Dr. Kexin Chen at Tianjin Medical University Cancer Institute and Hospital. Dr. Zhang demonstrated that ryanodin receptor gene 3 (RYR3) that encodes a large protein involved in calcium channel, is important for breast cancer cell growth, morphology and migration. She identified a putative binding site for microRNA-367 (miR-367) located in the 3'-untranslated region (3'-UTR) of the RYR3 gene. She then identified a novel SNP within the miR-367 binding site that affects breast cancer risk, calcification, and patient survival. Her PhD thesis work resulted in a publication in Proceedings of National Academy of Sciences, USA (PNAS). Currently, she is focused on functional validations studies of discoveries from the Genome Wide Association Studies (GWAS) and has accumulated evidence that an unknown gene C6orf97 is important for breast cancer. Dr. Zhang’s studies have been published in high-impact journal in biomedical research including PNAS, PLoS One, Breast Cancer Research and Treatment, and PLoS Genetics. After a highly productive training in Dr. Wei Zhang’s laboratory at the M.D. Anderson Cancer Center, Dr. Zhang returned to her cancer institute & hospital in Tianjin, China in 2011.
As an oncology surgeon specializing in breast cancer, a major disease that afflicts women in China and in the world, she continues to work with Dr. Chen and colleagues on a GWAS project in breast cancer as well as being an active member of the surgery team. Dr. Zhang was a key research investigator on two grants from the Natural Science Foundation of China (NSFC) and recently successfully competed for a NSFC grant as a young principal investigator. In 2011, she won the first prize in research competition at the Tianjin Medical University. I n 2011, her research was highlighted as an example showing that Chinese trainees returned to China and became the driving force of cancer research in China in an article published by the Cancer Discovery, a flagship journal of American Association of Cancer Research (AACR). AACR is the largest non-profit society in cancer research in USA. Dr. Zhang is dedicated to breast cancer research and treatments in China.
Selected Publications:
1. ZhangL,LiuY,SongF,ZhengH,HuL,HongLu,LiuP,HaoX,ZhangW,ChenK. A functional SNP in the miR-367 binding site in the 3'UTR of the calcium channel gene RYR3 affects breast cancer risk and calcification. Proc Natl Acad Sci U S A. 2011,16;108(33):13653-8.
2. Cheng H, Zhang L, Cogdell D, Zheng H, Scatter A, Nykter M, Harris C, Chen K, Hamilton S, Zhang W. Circulating Plasma MiR-141 is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis. Plos One, 2011,6(3):e17745. (co-first author)
3. Zhang L, Gu L, Qian B, Hao X, Zhang W, Wei Q, Chen K. Association of genetic polymorphisms of ER-alpha and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women. Breast Cancer Res Treat, 2009,114(2):327-338.
4. Dai H, Zhang L, Cao M, Song F, Zheng H, Zhu X, Wei Q, Zhang W, Chen K. The
role of polymorphisms in circadian pathway genes in breast tumorigenesis.
Breast Cancer Res Treat, 2011,127(2):531-40. 5. LongJ,CaiQ,ShuXO,QuS,LiC,ZhengY,GuK,WangW,XiangYB,ChengJ,
Chen K, Zhang L, Zheng H, Shen CY, Huang CS, Hou MF, Shen H, Hu Z, Wang F, Deming SL, Kelley MC, Shrubsole MJ, Khoo US, Chan KY, Chan SY, Haiman CA, Henderson BE, Le Marchand L, Iwasaki M, Kasuga Y, Tsugane S, Matsuo K, Tajima K, Iwata H, Huang B, Shi J, Li G, Wen W, Gao YT, Lu W, Zheng W. Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. PLoS Genet,2010,24;6(6):e1001002.
Dr. Yi Zhang, Department of Pharmacology at the College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu.
Dr. Yi Zhang is currently a lecturer in the Department of Pharmacology at the College of Pharmaceutical Sciences, Soochow University. Dr. Zhang attended Suzhou Medical College (now Soochow University) in China, and graduated summa cum laude in his class with a Major in pharmacy. He also received his master in 2004 and Ph.D. degrees in 2012 in Pharmacology from Soochow University.
In May, 2010, Yi Zhang joined Dr. Jin-Ming Yang's lab as a visiting scholar at the Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. At the Penn State, Dr. Zhang studied the role and mechanisms of nucleus accumbens-1 (NAC1, a transcriptional co-factor that belongs to the BTB/POZ gene family) in cancer development and progression. Dr. Zhang demonstrated an oncogenic role of NAC1 that is closely associated with the molecular function of this transcriptional co-factor in controlling autophagy and cellular senescence. He found that under stress conditions, NAC1 activates autophagy via modulating the expression and translocation of HMGB1 (a highly conserved chromatin-associated nuclear proteinfunctioning as a critical regulator of autophagy). Yi also showed that NAC1-mediated autophagy affects the efficacy of cisplatin-induced cancer cell death. These results not only shed new lights on the molecular regulation of autophagy, but also provide a better approach to achieve maximum therapeutic benefits of cisplatin, a commonly used chemotherapeutic drug for cancer treatment. This work was published in Oncogene in Feb of 2012. In another research project, Dr. Zhang identified NAC1 as a previously unrecognized suppressor of senescence that affects pathogenesis of tumor development and progression. This part of work was published in Cancer Research in August of 2012. During his two-years training with Dr. Yang, Yi published a total of 5 papers as the first author in Oncogene, Cancer Res, Autophagy, Biochemical and Biophysical Research Communication and Acta Pharmacologic Sinica. Additionally, he is the co-first author or coauthor in a number of publications in Cancer Research, Molecular
Cancer Therapeutics, and PLoS ONE as well as in a book chapter. In May 2012, Dr. Zhang returned to College of Pharmaceutical Sciences, Soochow University. In addition to teaching, Dr. Zhang continues to pursue his independent research and also collaborates with his colleagues in Suzhou, Shanghai (China) and Hershey (USA). Dr. Zhang's studies are currently supported by the Natural Science Foundation of China, Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the ince College Natural Science Foundation, and Soochow University. Dr. Zhang's achievements have clearly demonstrated his potential for excellence and future contribution to cancer
research.
Selected publications: 1. Zhang Y, Cheng Y, Ren X, Hori T, Huber-Keener KJ, Zhang L, Yap KL, Liu D,
Shantz L, Qin ZH, Zhang S, Wang J, Wang HG, Shih IeM, Yang JM. Dysfunction of Nucleus Accumbens-1 Activates Cellular Senescence and Inhibits Tumor Cell Proliferation and Oncogenesis. Cancer Res. 2012 Aug 15;72(16):4262-75.
2. Zhang Y, Cheng Y, Ren X, Zhang L, Yap KL, Wu H, Patel R, Liu D, Qin ZH, Shih IM, Yang JM. NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response. Oncogene. 2012, 31(8),1055-1064.
3. Zhang Y, Yang JW, Ren X, Yang JM. NAC1 and HMGB1 enter a partnership for manipulating autophagy. Autophagy. 2011 Dec;7(12):1557-8.
Jiangsu Prov
Zhang Y, Cheng Y, Zhang L, Ren X, Huber-Keener KJ, Lee S, Yun J, Wang HG, Yang JM. Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression. BiochemBiophys Res Commun. 2011 Oct 14; 414(1):129-34.
Zhang L#, Zhang Y#, Liu XY, Qin ZH, Yang JM. Expression of elongation factor-2 kinase contributes to anoikis resistance and invasion of human glioma cells. ActaPharmacol Sin. 2011 Mar;32(3):361-7. (# these authors contributed equally to this study)
Dr. Yuhua Zhao, Department of Biochemistry and Molecular Biology, Sichuan University, Chengdu, Sichuan
Dr. Yuhua Zhao, currently an associate professor at the Department of Biochemistry and Molecular Biology, Sichuan University, received her bachelor degree in Pharmacy from West China University of Medical Sciences in 1992, master degree in Biochemistry from West China University of Medical Sciences in 1995, and Ph. D. degree in Biochemistry and Molecular Biology from the Sichuan University in 2003.
In July 2007, Dr. Zhao joined Dr. Ming Tan's laboratory at the Mitchell Cancer Institute of University of South Alabama, Mobile, Alabama, USA as a postdoctoral fellow. Dr. Zhao's research projects focused on glucose metabolism and ErbB2-mediated breast
cancer progression. For the first time, Dr. Zhao found that in human breast cancer cells, ErbB2 promotes glycolysis through the HSF1-mediated upregulation of LDH-A, which may have a major role in regulating glucose metabolism in breast cancer cells. This work was published on Oncogene and attracted significant interests from cancer research community and the local news media. In another research project, Dr. Zhao showed that increased glycolysis contributes to trastuzumab resistance and combining trastuzumab with glycolysis inhibition synergistically suppressed trastuzumab-sensitive and-resistant breast cancers. These results were published on Cancer Research and featured on the Homepage of the journal and in Nature/SciBX.
In August 2010, Dr. Zhao returned to the Sichuan University to continue her career as both a teacher and researcher. She continues to work on targeted treatment of breast cancer and is actively seeking for extramural funding from Chinese government. Meanwhile she is diligently working to establish a collaborative research laboratory that focuses on cancer metabolism between Sichuan University and Mitchell Cancer Institute at the University of South Alabama. The goal of Dr. Zhao’s researchis to translate the knowledge acquired in the laboratory into clinical prognosis and treatments for human cancers.
Selected Publications 1. Zhao Y, Liu H, Liu Z, Ding Y, LeDoux SP, Wilson GL, Voellmy R, Lin Y, Lin W,
Nahta R, Liu B, Fodstad O, Chen J, Wu Y, Price JE, and Tan M. Overcoming Trastuzumab Resistance in ErbB2-Positive Breast Cancer by Targeting Dysregulated Glucose Metabolism. Cancer Research, 2011, 71(13); 4585-97.
2. ZhaoY,LiuH,RikerAI,FodstadO,LedouxSP,WilsonGL,TanM.Emerging metabolic targets in cancer therapy. Frontiers in Bioscicences,2011, 16:1844-1860.
3. ZhouM*,ZhaoY*,DingY*,LiuH,LiuZ,FodstadO,RikerAI,Kamarajugadda S, Lu J, Owen LB, Ledoux SP, Tan M. Inhibition of lactatedehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol. Molecular Cancer, 2010, 9(1):33. (* these authors contributed equally).
Zhao Y, Weng CC, Tong M, Wei J, Tai HH. Restoration of leukotriene B(4)-12-hydroxydehydrogenase/15-, oxo-prostaglandin 13-reductase (LTBDH/PGR) expression inhibits, lung cancer growth in vitro and in vivo. Lung Cancer, 2010, 68(2): 161-169
Zhao Y, Zhou M, Liu H, Ding Y, Khong HT, Yu D, Fodstad O, Tan M. Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth. Oncogene, 2009, 28(42): 3689-3701.