Dr. Fan-Minogue received an MD from Peking Union Medical College, and a PhD in Cell Biology under the mentorship of Dr. David Bedwell at UAB. She came to Stanford as a fellow of the NCI R25T Molecular Imaging Scholars Training Program and performed postdoctoral research under the mentorship of Dr. Sanjiv Gambhir on non-invasive molecular imaging of cancer cell signaling. She then completed a masters degree in Bioinformatics at Stanford funded by the NLM Biomedical Informatics Training grant and performed translational bioinformatics research under the mentorship of Dr. Atul Butte. In 2015, she joined Dr. Kari Nadeau's lab and is currently an Instructor in Pulmonary & Critical Care Medicine. With extensive years of training and research experience in basic science, translational medicine and systems biology, Dr. Fan-Minogue has developed a long-term research goal centered on improving the understanding of the molecular mechanism of human diseases and expediting the translation of research discovery by integrating multi-disciplinary approaches.
Instructor, Medicine - Pulmonary & Critical Care Medicine
Honors & Awards
PSB Travel Award, 2015 Pacific Symposium on Biocomputing (2014)
AACR-Aflac Scholar-in-Training Award, American Association for Cancer Research (AACR) (2013)
Awardee for Attending Future Faculty Workshop, Rice's NSF ADVANCE Program (2012)
Best Poster Award, Biomedical Computation at Stanford (BCATS) (2012)
Grand Prize ($20K) at the Innovate 4 Healthcare IT Challenge, Center for Health Information and Decision Systems (CHIDS) and Johnson&Johnson (2012)
NLM Informatics Postdoctoral Master Fellowship, Stanford University (2012)
NLM Informatics Fellowship, Columbia University (declined) (2011)
AACR-Merck Scholar-in-Training Award, American Association of Cancer Research (2010)
National Summit on Gender and the Postdoctorate Travel Grants, National Postdoctoral Association (2010)
Travel Fellowship, Helena Anna Henzl Gabor Young Women in Science Fund (2009)
Stanford Molecular Imaging Scholar, NCI R25T Training Grant (2007)
Best Platform Presentation, 13th Southeastern Regional Yeast Meeting (2006)
1st place Oral Presenation, 16th Microbiology Research Retreat (2005)
Boards, Advisory Committees, Professional Organizations
Assigned Reviewer, AMIA Joint Summits on Translational Science (2014 - Present)
Member, ASHG, The American Society of Human Genetics (2014 - Present)
Member, ISCB: International Society for Computational Biology (2014 - Present)
Member, AMIA: American Medical Informatics Association (2012 - Present)
Member, AWIS: Association for Women in Science (2011 - Present)
Member, AAUW: American Association of University Women (2011 - Present)
Member, WMIS: World Molecular Imaging Society (2011 - 2013)
cofounder, Asian Women in STEM (2010 - 2011)
Associate Member, WICR: Women in Cancer Research (2009 - Present)
Associate Member, AACR: American Association for Cancer Research (2009 - Present)
Committee Member, CBIS 1st Annual Symposium Organizing Committee (2009 - 2010)
Member, AMI: Academy of Molecular Imaging (2008 - 2011)
Member, SMI: Society of Molecular Imaging (2008 - 2011)
M.S., Stanford University, BIOM-MS (2013)
Ph.D., University of Alabama at Birmingham, Cell Biology (2007)
M.D., Peking Union Medical College, Medicine (2002)
Hua Fan Minogue, Sanjiv Sam Gambhir. "United States Patent US-2012-0270914-A1 Split-Luciferase c-Myc sensor and uses thereof", Leland Stanford Junior University, Oct 1, 2012
Current Research and Scholarly Interests
Dr. Fan-Minogue's current research is under the mentorship of Dr. Kari Nadeau and with a focus on understanding the immune mechanism of asthma and food allergy by utilizing single cell-based genomics technologies and immuno-informatics approaches.
A systematic assessment of linking gene expression with genetic variants for prioritizing candidate targets.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
2015; 20: 383-394
Gene expression and disease-associated variants are often used to prioritize candidate genes for target validation. However, the success of these gene features alone or in combination in the discovery of therapeutic targets is uncertain. Here we evaluated the effectiveness of the differential expression (DE), the disease-associated single nucleotide polymorphisms (SNPs) and the combination of the two in recovering and predicting known therapeutic targets across 56 human diseases. We demonstrate that the performance of each feature varies across diseases and generally the features have more recovery power than predictive power. The combination of the two features, however, has significantly higher predictive power than each feature alone. Our study provides a systematic evaluation of two common gene features, DE and SNPs, for prioritization of candidate targets and identified an improved predictive power of coupling these two features.
View details for PubMedID 25592598
Relating hepatocellular carcinoma tumor samples and cell lines using gene expression data in translational research.
BMC medical genomics
2015; 8: S5-?
Cancer cell lines are used extensively to study cancer biology and to test hypotheses in translational research. The relevance of cell lines is dependent on how closely they resemble the tumors being studied. Relating tumors and cell lines, and recognizing their similarities and differences are thus very important for translational research. Rapid advances in genomics have led to the generation of large volumes of genomic and transcriptomic data for a diverse set of primary cancer samples, normal tissue samples and cancer cell lines. Hepatocellular Carcinoma (HCC) is one of the most common tumors worldwide, with high occurrence in Asia and sub-Saharan regions. The current effective treatments of HCC remain limited. In this work, we compared the gene expression measurements of 200 HCC tumor samples from The Cancer Genome Atlas and over 1000 cancer cell lines including 25 HCC cancer cell lines from Cancer Cell Line Encyclopedia. We showed that the HCC tumor samples correlate closely with HCC cell lines in comparison to cell lines derived from other tumor types. We further demonstrated that the most commonly used HCC cell lines resemble HCC tumors, while we identified nearly half of the cell lines that do not resemble primary tumors. Interestingly, a substantial number of genes that are critical for disease development or drug response are either expressed at low levels or absent among highly correlated cell lines; additional attention should be paid to these genes in translational research. Our study will be used to guide the selection of HCC cell lines and pinpoint the specific genes that are differentially expressed in either tumors or cell lines.
View details for DOI 10.1186/1755-8794-8-S2-S5
View details for PubMedID 26043652
The Integrative Human Microbiome Project: Dynamic Analysis of Microbiome-Host Omics Profiles during Periods of Human Health and Disease
CELL HOST & MICROBE
2014; 16 (3): 276-289
Much has been learned about the diversity and distribution of human-associated microbial communities, but we still know little about the biology of the microbiome, how it interacts with the host, and how the host responds to its resident microbiota. The Integrative Human Microbiome Project (iHMP, http://hmp2.org), the second phase of the NIH Human Microbiome Project, will study these interactions by analyzing microbiome and host activities in longitudinal studies of disease-specific cohorts and by creating integrated data sets of microbiome and host functional properties. These data sets will serve as experimental test beds to evaluate new models, methods, and analyses on the interactions of host and microbiome. Here we describe the three models of microbiome-associated human conditions, on the dynamics of preterm birth, inflammatory bowel disease, and type 2 diabetes, and their underlying hypotheses, as well as the multi-omic data types to be collected, integrated, and distributed through public repositories as a community resource.
View details for DOI 10.1016/j.chom.2014.08.014
View details for Web of Science ID 000342057000006
View details for PubMedID 25211071
Preclinical Efficacy of the Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab in a Mouse Brain Orthotopic Glioma Model Evaluated by Bioluminescence, PET, and MRI
CLINICAL CANCER RESEARCH
2013; 19 (20): 5711-5721
Ficlatuzumab is a novel therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize extensive preclinical work using this agent in a mouse brain orthotopic model of glioblastoma.Sequential experiments were done using eight- to nine-week-old nude mice injected with 3 × 10(5) U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were conducted first. Subsequently, various small-animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and MRI, were used with a U87 MG-Luc 2 stable cell line, with and without the use of ficlatuzumab, to evaluate the ability to noninvasively assess tumor growth and response to therapy. ANOVA was conducted to evaluate for significant differences in the response.There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-D-thymidine (FLT) PET provided a better signal-to-background ratio than 2[(18)F]fluoro-2-deoxy-d-glucose (FDG) PET. In addition, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later.Targeting the HGF/c-MET pathway with the novel agent ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy. Given the clinical applicability of these findings, future studies on patients with glioblastoma may be appropriate.
View details for DOI 10.1158/1078-0432.CCR-12-1015
View details for Web of Science ID 000325797600019
A c-Myc Activation Sensor-Based High-Throughput Drug Screening Identifies an Antineoplastic Effect of Nitazoxanide
MOLECULAR CANCER THERAPEUTICS
2013; 12 (9): 1896-1905
Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor based high throughput-screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is established from a pure clone of a stable breast cancer cell line that constitutively expresses a c-Myc activation sensor. Optimization of the assay performance in the HTS format resulted in uniform and robust signals at the baseline. Using this system, we performed a quantitative HTS against approximately 5,000 existing bioactive compounds from five different libraries. Thirty-nine potential hits were identified, including currently known c-Myc inhibitors. There are a few among the top potent hits that are not known for anti-c-Myc activity. One of these hits is nitazoxanide (NTZ), a thiazolide for treating human protozoal infections. Validation of NTZ in different cancer cell lines revealed a high potency for c-Myc inhibition with IC50 ranging between 10 - 500nM. Oral administration of NTZ in breast cancer xenograft mouse models significantly suppressed tumor growth by inhibition of c-Myc and induction of apoptosis. These findings suggest a potential of NTZ to be repurposed as a new anti-tumor agent for inhibition of c-Myc associated neoplasia. Our work also demonstrated the unique advantage of molecular imaging in accelerating discovery of drugs for c-Myc targeted cancer therapy.
View details for DOI 10.1158/1535-7163.MCT-12-1243
View details for Web of Science ID 000324174600019
View details for PubMedID 23825064
- Mining Cancer Genomics Data for Identification of Cancer Stem Cell Targets The Journal of Nuclear Medicine 2013; Jan 25 (10)
- Extracting Computational and Semantic Features from Portable Chest X-rays for Diagnosis of Acute Respiratory Distress Syndrome 2013: 64
- A quantitative high throughput molecular imaging based drug screening identifies an anti-protozoal drug as an anti-cancer agent for its inhibitory effect on the c-Myc oncoprotein Molecular Imaging and Biology 2012; Feb (14)
MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase
2011; 71 (6): 2286-2297
MYC is a potential target for many cancers but is not amenable to existing pharmacologic approaches. Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) by statins has shown potential efficacy against a number of cancers. Here, we show that inhibition of HMG-CoA reductase by atorvastatin (AT) blocks both MYC phosphorylation and activation, suppressing tumor initiation and growth in vivo in a transgenic model of MYC-induced hepatocellular carcinoma (HCC) as well as in human HCC-derived cell lines. To confirm specificity, we show that the antitumor effects of AT are blocked by cotreatment with the HMG-CoA reductase product mevalonate. Moreover, by using a novel molecular imaging sensor, we confirm that inhibition of HMG-CoA reductase blocks MYC phosphorylation in vivo. Importantly, the introduction of phosphorylation mutants of MYC at Ser62 or Thr58 into tumors blocks their sensitivity to inhibition of HMG-CoA reductase. Finally, we show that inhibition of HMG-CoA reductase suppresses MYC phosphorylation through Rac GTPase. Therefore, HMG-CoA reductase is a critical regulator of MYC phosphorylation, activation, and tumorigenic properties. The inhibition of HMG-CoA reductase may be a useful target for the treatment of MYC-associated HCC as well as other tumors.
View details for DOI 10.1158/0008-5472.CAN-10-3367
View details for Web of Science ID 000288381300028
View details for PubMedID 21262914
Noninvasive molecular imaging of c-Myc activation in living mice
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2010; 107 (36): 15892-15897
The cytoplasmic Myc protein (c-Myc) regulates various human genes and is dysregulated in many human cancers. Phosphorylation mediates the protein activation of c-Myc and is essential for the function of this transcription factor in normal cell behavior and tumor growth. To date, however, the targeting of Myc as a therapeutic approach for cancer treatment has been achieved primarily at the nonprotein level. We have developed a molecular imaging sensor for noninvasive imaging of c-Myc activity in living subjects using a split Firefly luciferase (FL) complementation strategy to detect and quantify the phosphorylation-mediated interaction between glycogen synthase kinase 3beta (GSK3beta) and c-Myc. This sensor system consists of two fusion proteins, GSK 35-433-CFL and NFL-c-Myc, in which specific fragments of GSK3beta and c-Myc are fused with C-terminal and N-terminal fragments of the split FL, respectively. The sensor detects phosphorylation-specific GSK3beta-c-Myc interaction, the imaging signal of which correlates with the steady-state and temporal regulation of c-Myc phosphorylation in cell culture. The sensor also detects inhibition of c-Myc activity via differential pathways, allowing noninvasive monitoring of c-Myc-targeted drug efficacy in intact cells and living mice. Notably, this drug inhibition is detected before changes in tumor size are apparent in mouse xenograft and liver tumor models. This reporter system not only provides an innovative way to investigate the role of functional c-Myc in normal and cancer-related biological processes, but also facilitates c-Myc-targeted drug development by providing a rapid quantitative approach to assessing cancer response to therapy in living subjects.
View details for DOI 10.1073/pnas.1007443107
View details for Web of Science ID 000281637800049
View details for PubMedID 20713710
- Molecular Imaging of Oncogene Targeted Cancer Therapy Molecular Imaging and Biology 2010; 12 (1)
- Comparison of 18F-FDG and 18F-FLT small-animal PET imaging in an orthotopic glioblastoma mouse model Molecular Imaging and Biology 2010; 12 (2)
- Secretory Gaussia Luciferase (Sgluc)-Monomeric Red Fluorescence Protein (Mrfp)-Truncated Herpes Simplex VirusThymidine Kinase (Ttk) Triple Fusion Improves Intracellular Luciferase Activity and Enhances its Imaging Applications in Small Animals Molecular Imaging and Biology 2010; 12 (1)
- Molecular Imaging of Protein-Protein Interactions Molecular Imaging: Principles and Practice 2010
- Reporter Gene Imaging of Cell Signal Transduction Molecular Imaging with Reporter Genes 2010
Connection between stop codon reassignment and frequent use of shifty stop frameshifting
RNA-A PUBLICATION OF THE RNA SOCIETY
2009; 15 (5): 889-897
Ciliated protozoa of the genus Euplotes have undergone genetic code reassignment, redefining the termination codon UGA to encode cysteine. In addition, Euplotes spp. genes very frequently employ shifty stop frameshifting. Both of these phenomena involve noncanonical events at a termination codon, suggesting they might have a common cause. We recently demonstrated that Euplotes octocarinatus peptide release factor eRF1 ignores UGA termination codons while continuing to recognize UAA and UAG. Here we show that both the Tetrahymena thermophila and E. octocarinatus eRF1 factors allow efficient frameshifting at all three termination codons, suggesting that UGA redefinition also impaired UAA/UAG recognition. Mutations of the Euplotes factor restoring a phylogenetically conserved motif in eRF1 (TASNIKS) reduced programmed frameshifting at all three termination codons. Mutation of another conserved residue, Cys124, strongly reduces frameshifting at UGA while actually increasing frameshifting at UAA/UAG. We will discuss these results in light of recent biochemical characterization of these mutations.
View details for DOI 10.1261/rna.1508109
View details for Web of Science ID 000265231500014
View details for PubMedID 19329535
Distinct eRF3 requirements suggest alternate eRF1 conformations mediate peptide release during eukaryotic translation termination
2008; 30 (5): 599-609
Organisms that use the standard genetic code recognize UAA, UAG, and UGA as stop codons, whereas variant code species frequently alter this pattern of stop codon recognition. We previously demonstrated that a hybrid eRF1 carrying the Euplotes octocarinatus domain 1 fused to Saccharomyces cerevisiae domains 2 and 3 (Eo/Sc eRF1) recognized UAA and UAG, but not UGA, as stop codons. In the current study, we identified mutations in Eo/Sc eRF1 that restore UGA recognition and define distinct roles for the TASNIKS and YxCxxxF motifs in eRF1 function. Mutations in or near the YxCxxxF motif support the cavity model for stop codon recognition by eRF1. Mutations in the TASNIKS motif eliminated the eRF3 requirement for peptide release at UAA and UAG codons, but not UGA codons. These results suggest that the TASNIKS motif and eRF3 function together to trigger eRF1 conformational changes that couple stop codon recognition and peptide release during eukaryotic translation termination.
View details for DOI 10.1016/j.molcel.2008.03.020
View details for Web of Science ID 000256644100010
View details for PubMedID 18538658
Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity
RNA-A PUBLICATION OF THE RNA SOCIETY
2008; 14 (1): 148-157
Recent studies of prokaryotic ribosomes have dramatically increased our knowledge of ribosomal RNA (rRNA) structure, functional centers, and their interactions with antibiotics. However, much less is known about how rRNA function differs between prokaryotic and eukaryotic ribosomes. The core decoding sites are identical in yeast and human 18S rRNAs, suggesting that insights obtained in studies with yeast rRNA mutants can provide information about ribosome function in both species. In this study, we examined the importance of key nucleotides of the 18S rRNA decoding site on ribosome function and aminoglycoside susceptibility in Saccharomyces cerevisiae cells expressing homogeneous populations of mutant ribosomes. We found that residues G577, A1755, and A1756 (corresponding to Escherichia coli residues G530, A1492, and A1493, respectively) are essential for cell viability. We also found that residue G1645 (A1408 in E. coli) and A1754 (G1491 in E. coli) both make significant and distinct contributions to aminoglycoside resistance. Furthermore, we found that mutations at these residues do not alter the basal level of translational accuracy, but influence both paromomycin-induced misreading of sense codons and readthrough of stop codons. This study represents the most comprehensive mutational analysis of the eukaryotic decoding site to date, and suggests that many fundamental features of decoding site function are conserved between prokaryotes and eukaryotes.
View details for DOI 10.1261/rna.805208
View details for Web of Science ID 000251698200015
View details for PubMedID 18003936
Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes
MOLECULAR AND CELLULAR BIOLOGY
2006; 26 (2): 438-447
The reassignment of stop codons is common among many ciliate species. For example, Tetrahymena species recognize only UGA as a stop codon, while Euplotes species recognize only UAA and UAG as stop codons. Recent studies have shown that domain 1 of the translation termination factor eRF1 mediates stop codon recognition. While it is commonly assumed that changes in domain 1 of ciliate eRF1s are responsible for altered stop codon recognition, this has never been demonstrated in vivo. To carry out such an analysis, we made hybrid proteins that contained eRF1 domain 1 from either Tetrahymena thermophila or Euplotes octocarinatus fused to eRF1 domains 2 and 3 from Saccharomyces cerevisiae. We found that the Tetrahymena hybrid eRF1 efficiently terminated at all three stop codons when expressed in yeast cells, indicating that domain 1 is not the sole determinant of stop codon recognition in Tetrahymena species. In contrast, the Euplotes hybrid facilitated efficient translation termination at UAA and UAG codons but not at the UGA codon. Together, these results indicate that while domain 1 facilitates stop codon recognition, other factors can influence this process. Our findings also indicate that these two ciliate species used distinct approaches to diverge from the universal genetic code.
View details for Web of Science ID 000234676100005
View details for PubMedID 16382136
- Distinct paths to stop-codon reassignment in the ciliates Tetrahymena thermaphila and Euplotes octocarinatus Journal of Eukaryotic Microbiology 2006
- The insight of NF-kB activation and inhibition: the hopeful future therapy in clinic? Journal of Chinese Practical Surgery 2002