A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE

Shen, Binghui, Ph.D.

Laboratory of Binghui Shen, Ph.D.
The Shen laboratory has carried out various major National Institutes of Health-funded projects. In addition, we collaborate with Dr. Yuejin Hua of Zhejiang University, China, in the study of radiation-induced DNA damage responses in Deinococcus radiodurans.
 
Research Environment
The laboratory is located in the Beckman Research Institute at City of Hope in Duarte, California. Duarte is in the northeast suburbs of Los Angeles, just outside Pasadena, nestled in the foothills of the San Gabriel mountains. We're close to all of the entertainment and scenic attractions Southern California has to offer, yet far enough removed from the big city buzz. Take a half hour drive to the beach, or an hour and a half to local skiing. The medical center and Beckman Research Institute are situated on a beautiful, 112-acre campus, and our lab is housed in the Kaplan-Black Research Building.
 
Approximately 25 NCI-supported core facilities are available for biomedical research in City of Hope as a Comprehensive Cancer Center research facility. These include: microarray, mass-spectroscopy/protein sequencing, DNA sequencing, oligonucleotide & peptide synthesis, phosphor- and fluoro-imaging, histology/histochemistry, frozen tumor bank, time-lapse videography, confocal and electron microscopies, cytogenetics, NMR, flow-cytometry, molecular modeling, transgenic mice, and animal care.
 
An active Postdoctoral Association (PDA) promotes interaction between the Institute and postdoctoral fellows and graduate students, to help to ensure that their transition is smooth and their time here is as fulfilling as possible
 

Research

DNA Replication, Repair, and Apoptosis Nucleases in Genome Stability and Cancer
DNA replication and repair are critical for maintaining genome stability. These processes are in part dependent on the activities of an emerging family of structure-specific nucleases. Flap EndoNuclease 1 (FEN1) is a metallo- and substrate structure specific- nuclease. It possesses three distinct biochemical activities, functioning as a flap endonuclease (FEN), a nick-specific exonuclease (EXO), and a gapdependent endonuclease (GEN). FEN1 plays a critical role in maintaining human genome stability via six different pathways. It serves as a major nuclease for RNA primer removal during Okazaki fragment maturation and for long patch base excision repair using its FEN activity. Its concerted action of EXO and GEN activities is critical in resolution of di- and tri- nucleotide repeat secondary structures and stalled DNA replication forks, as well as in apoptotic cell DNA fragmentation. It also plays a major role in maintenance of telomere stability.
 
The multiple functions of FEN1 are regulated via three major mechanisms: formation of complexes with different protein partners, cellular compartmentation, and post-translational modifications. More than 30 proteins have been identified to interact with FEN1, forming specific complexes in different pathways. Upon acetylation, FEN1 translocates into the nucleus in response to DNA damage and cell cycle phase changes. It is very much enhanced in the nucleolus for maintenance of stability of tandem repeats of ribosomal DNA. FEN1 is also in mitochondrion, playing an important role in mitochondrial DNA replication and repair. The nuclease is acetylated, phosphorylated or methylated in different molecular events and the interaction between methylation and phosphorylation determines its recruitment onto DNA replication forks via proliferating cell nuclear antigen. The first group of FEN1 somatic mutations has been identified in human cancer cells, which has clear segregation of biochemical activities. The future emphasis will be placed on the mutations and prevalent polymorphisms that may impair one of the three major regulatory mechanisms. See Project 1  - Functional Analysis of FEN-1 Nuclease in Genome Stability.
 
Recently, we found that another major nuclease, DNA2, is dominantly localized into mitochondria and cooperatively processes replication and repair DNA intermediates for ligation and completion of circular mtDNA replication and repair. These novel and exciting observations prompted us to: i) knock out the DNA2 gene in mice to determine if defective DNA2-mediated RNA primer removal causes mitochondrial genomic instabilities, consequently promoting cancers and other genetic diseases, and ii) link functional defects of the DNA2 mutations identified in human mitochondrion-based diseases to pathologic mechanisms. Information made available from these studies should establish a relationship among the functions of these novel mitochondrial genes, unique mitochondrial mutagenic phenotype(s), and pathological mechanisms. The proposed study may also establish a foundation for the development of new treatment regimens for patients with mitochondrion-based cancers and other disorders. See Project 2 - Role of Nucleases in RNA Primer Removal and Mutagenesis.
 
The other novel nuclease that we are interested in is called TatD, which possesses a nick and 3’ exonuclease activity and is involved in apoptosis DNA fragmentation. In collaboration with Dr. John Williams in the Department of Molecular Medicine, we are currently undertaking a detailed 3-D structural and functional analysis of TatD to determine its role in apoptosis and the biological consequences, in human cells, of defects in this nuclease.
 

Project 1

Functional analysis of FEN1 nuclease in genome stability
The project was funded by NCI to test a hypothesis that subtle deficiency or defects in the individual biochemical activities of FEN1 may lead to different phenotypes in yeast and different susceptibilities in the human population to environmental stresses and individual differences in the onset of genetic diseases.
 
Figure to the right: E160D FEN1 mice are highly susceptible to cancers as a result of their mutator phenotype and chronic inflammation. The panel shows the chronic inflammation and Tumorigenesis in the lung. Top, disease incidence at specific life stages (timeline in months) of wild-type (WT), Fen1ED/+ (ED/+) and Fen1ED/ED (ED/ED) mice. Below, histology (H&E) of normal lung, lung with chronic inflammation, adenoma and adenocarcinoma in ED/ED mice. From: Zheng et al., 2008 Nature Medicine.
 

Project 2

Role of nuclease in RNA primer removal and mutagenesis
The major goals of this project are to carry out experiments to test roles of several eukaryotic nuclease complexes in RNA primer removal during lagging strand DNA synthesis in nuclei and mitochondria, and to examine the mutagenic consequences of defects of the individual nuclease complexes.
 
Localization of hDNA2 and mitochondria-lspecific heat-shock protein 70 (mtHSP70) in HeLa cells. hDNA2 (red) and mtHSP70 (green) were stained with antibodies to hDNA2 and mtHSP70. The nucleus (blue) was stained with DAPI. Yellow spots (arrows) indicate co-localization of hDNA2 and mtHSP70 (merged views). The square box in the upper right panel is a magnification of the area framed in white.
 

Lab Members

Huifang Dai, B.S.
Sr. Research Associate
Ph 626-256-HOPE (4673), ext. 63818
Fax 626-301-8892
hdai@coh.org
 
Joonas Jamsen, Ph.D.
Postdoctoral Fellow
Ph. 626-256-HOPE (4673), ext. (W/A)
Fax 626-301-8892
jjamsen@coh.org
 
Weiqiang Lin, Ph.D.
Postdoctoral Fellow
Ph. 626-256-HOPE (4673), ext.64146
Fax 626-301-8892
wlin@coh.org
 
Guojun Lin, Ph.D.
Postdoctoral Fellow
Ph. 626-256-HOPE (4673), ext. 63818
Fax 626-301-8892
glu@coh.org
 
David Onyango, Ph.D.
Postdoctoral Fellow
Ph. 626-256-HOPE (4673), ext. 65284
Fax 626-301-8892
donyango@coh.org
 
Julie Kanjanapangka
Graduate Student
Ph 626-256-HOPE (4673), ext. 62935
Fax 626-301-8892
jkanjanapangka@coh.org
 
Zhenxing Wu, M.S.
Predoctoral Fellow
Ph. 626-256-HOPE (4673), ext. 63518
Fax 626-301-8892
zhwu@coh.org
 
Li Zheng, Ph.D.
Assistant Research Professor
Ph 626-256-HOPE (4673), ext. 64147
Fax 626-301-8892
lzheng@coh.org
 
Mian Zhou, Ph.D.
Staff Scientist
Ph 626-256-HOPE (4673), ext. 64147
Fax 626-301-8892
mzhou@coh.org
 
Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
NEWS & UPDATES
  • For breast cancer survivors, a common worry is a recurrence of their cancer. Currently, these patients are screened with regular mammograms, but there’s no way to tell who is more likely to have a recurrence and who is fully cleared of her cancer. A new blood test – reported in Cancer Research, a journal of the...
  • Metastasis — the spreading of cancer cells from a primary tumor site to other parts of the body — generally leads to poorer outcomes for patients, so oncologists and researchers are constantly seeking new ways to detect and thwart this malicious process. Now City of Hope researchers may have identified a substa...
  • Deodorant, plastic bottles, grilled foods, artificial sweeteners, soy products … Do any of these products really cause cancer? With so many cancer myths and urban legends out there, why not ask the experts? They can debunk cancer myths while sharing cancer facts that matter, such as risk factors, preventi...
  • Cancer risk varies by ethnicity, as does the risk of cancer-related death. But the size of those differences can be surprising, highlighting the health disparities that exist among various ethnic groups in the United States. Both cancer incidence and death rates for men are highest among African-Americans, acco...
  • George Winston, known worldwide for his impressionistic, genre-defying music, considers music to be his first language, and admits he often stumbles over words – especially when he attempts languages other than English. There’s one German phrase he’s determined to perfect, however: danke schön. Winston thinks h...
  • Few decisions are more important than those involving health care, and few decisions can have such lasting impact, not only on oneself but on relatives and loved ones. Those choices, especially, should be made in advance – carefully, deliberately, free of pain and stress, and with much weighing of values and pr...
  • Using a card game to make decisions about health care, especially as those decisions relate to the end of life, would seem to be a poor idea. It isn’t. The GoWish Game makes those overwhelming, but all-important decisions not just easy, but natural. On each card of the 36-card deck is listed what seriously ill,...
  • Young adults and adolescents with cancer face unique challenges both during their treatment and afterward. Not only are therapies for children and older adults not always appropriate for them, they also must come to terms with the disease and treatment’s impact on their relationships, finances, school or ...
  • Breast cancer is the most common cancer, other than skin cancer, among women in the United States. It’s also the second-leading cause of cancer death, behind lung cancer. In the past several years, various task force recommendations and studies have questioned the benefits of broad screening guidelines fo...
  • Paternal age and the health effects it has on potential offspring have been the focus of many studies, but few have examined the effect parental age has on the risk of adult-onset hormone-related cancers (breast cancer, ovarian cancer and endometrial cancer). A team of City of Hope researchers, lead by Yani Lu,...
  • Hormone therapy, which is prescribed to women for relief of menopausal symptoms such hot flashes, night sweats and vaginal dryness, has recently seen a decline in popularity (and use) due to its link to an increased risk of breast and endometrial cancer. But City of Hope researchers have found that menopausal h...
  • Myeloproliferative neoplasms can’t be narrowed down to a single cancer, but they can be described by a defining characteristic: too many blood cells. The diseases bring with them a host of frustrating, potentially life-altering symptoms, and management of the diseases and their symptoms is crucial. An upcoming ...
  • More than 18,000 researchers, clinicians, advocates and other professionals will convene at the 105th American Association for Cancer Research (AACR) annual meeting taking place in San Diego from April 5 to 9. With more than 6,000 findings being presented over this five-day period, the amount of information can...
  • Cancer of the prostate is the No. 2 cancer killer of men, behind lung cancer, accounting for more than 29,000 deaths annually in this country. But because prostate cancer advances slowly, good prostate health and early detection can make all the difference. Many prostate cancer tumors don’t require immedi...
  • Despite advances made in detecting and treating nonsmall cell lung cancer, its prognosis remains grim. Even patients whose cancers are caught at their earliest stage have only a 50 percent chance of five-year survival. This poor prognosis is due in part to the cancer’s ability to resist treatment, renderi...