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Wei Gu, MD

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Locations and Hours

Stanford Blood Center

3373 Hillview Ave
MC 5556
Palo Alto, CA 94304
Phone: (650) 723-5252
Fax: (650) 725-6902
Map, Directions & Parking

Specialties

Clinical Pathology

Work and Education

Professional Education

Stanford University School of Medicine, Palo Alto, CA, 6/1/2014

Residency

UCSF Pathology Residency, San Francisco, CA, 6/30/17

Fellowship

UCSF Pathology Fellowships, San Francisco, CA, 06/30/2018

Board Certifications

Clinical Pathology, American Board of Pathology

Molecular Genetic Pathology, American Board of Pathology

All Publications

Associations of Early COVID-19 Cases in San Francisco with Domestic and International Travel. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Gu, W. n., Deng, X. n., Reyes, K. n., Hsu, E. n., Wang, C. n., Sotomayor-Gonzalez, A. n., Federman, S. n., Bushnell, B. n., Miller, S. n., Chiu, C. n. 2020

Abstract

In early-to-mid March 2020, 20 of 46 (43%) COVID-19 cases at a tertiary care hospital in San Francisco, California were travel-related. Cases were significantly associated with travel to Europe or New York (odds ratio 32.9). Viral genomes recovered from 9 of 12 (75%) cases co-clustered with lineages circulating in Europe.

View details for DOI 10.1093/cid/ciaa599

View details for PubMedID 32436571

View details for PubMedCentralID PMC7314204

Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids. Nature medicine Gu, W. n., Deng, X. n., Lee, M. n., Sucu, Y. D., Arevalo, S. n., Stryke, D. n., Federman, S. n., Gopez, A. n., Reyes, K. n., Zorn, K. n., Sample, H. n., Yu, G. n., Ishpuniani, G. n., Briggs, B. n., Chow, E. D., Berger, A. n., Wilson, M. R., Wang, C. n., Hsu, E. n., Miller, S. n., DeRisi, J. L., Chiu, C. Y. 2020

Abstract

We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182body fluids from 160patients withacute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.

View details for DOI 10.1038/s41591-020-1105-z

View details for PubMedID 33169017

Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California. Science (New York, N.Y.) Deng, X. n., Gu, W. n., Federman, S. n., du Plessis, L. n., Pybus, O. G., Faria, N. R., Wang, C. n., Yu, G. n., Bushnell, B. n., Pan, C. Y., Guevara, H. n., Sotomayor-Gonzalez, A. n., Zorn, K. n., Gopez, A. n., Servellita, V. n., Hsu, E. n., Miller, S. n., Bedford, T. n., Greninger, A. L., Roychoudhury, P. n., Starita, L. M., Famulare, M. n., Chu, H. Y., Shendure, J. n., Jerome, K. R., Anderson, C. n., Gangavarapu, K. n., Zeller, M. n., Spencer, E. n., Andersen, K. G., MacCannell, D. n., Paden, C. R., Li, Y. n., Zhang, J. n., Tong, S. n., Armstrong, G. n., Morrow, S. n., Willis, M. n., Matyas, B. T., Mase, S. n., Kasirye, O. n., Park, M. n., Masinde, G. n., Chan, C. n., Yu, A. T., Chai, S. J., Villarino, E. n., Bonin, B. n., Wadford, D. A., Chiu, C. Y. 2020; 369 (6503): 58287

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.

View details for DOI 10.1126/science.abb9263

View details for PubMedID 32513865

View details for PubMedCentralID PMC7286545

Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection. Annual review of pathology Gu, W. n., Miller, S. n., Chiu, C. Y. 2019; 14: 31938

Abstract

Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.

View details for DOI 10.1146/annurev-pathmechdis-012418-012751

View details for PubMedID 30355154

View details for PubMedCentralID PMC6345613

Brain Tumor Mutations Detected in Cerebral Spinal Fluid CLINICAL CHEMISTRY Pan, W., Gu, W., Nagpal, S., Gephart, M. H., Quake, S. R. 2015; 61 (3): 514-522

Abstract

Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood-brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative "liquid biopsy" of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined.We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease.We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from <5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations from the CSF of a patient with leptomeningeal disease by use of cancer panel sequencing, and the result was concordant with genetic testing on the primary tumor biopsy.Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care.

View details for DOI 10.1373/clinchem.2014.235457

View details for Web of Science ID 000352161300013

View details for PubMedID 25605683

Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia. Genetics in medicine Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

Abstract

Purpose:Prenatal diagnosis of fetal Mendelian disorders can benefit from noninvasive approaches using fetal cell-free DNA in maternal plasma. Detecting metabolic disorders before birth can result in immediate treatment postpartum in order to optimize outcome.Methods:We developed a mathematical model and an experimental methodology to analyze the case of a fetus with a 25% risk of inheriting two known mutations in MUT that cause methylmalonic acidemia. To accomplish this, we measured allelic counts at the mutation sites and the fetal fraction from high minor-allele-frequency single-nucleotide polymorphism positions.Results:By counting linked alleles, the test was able to distinguish 11 positive markers from the negative controls and thereby determine whether or not the mutations carried by the parents were inherited by the fetus. For a homozygous fetus, the Z-score of the mutation site was 5.97, whereas the median Z-score of all the linked alleles was 4.56 when all negative (heterozygous) controls had a Z-score <2.5.Conclusion:The application of this methodology for diagnosing methylmalonic acidemia shows that this is a cost-effective and noninvasive approach to diagnosing known mutations related to Mendelian disorders in the fetus.Genet Med advance online publication 9 January 2014Genetics in Medicine (2014); doi:10.1038/gim.2013.194.

View details for DOI 10.1038/gim.2013.194

View details for PubMedID 24406457

Non-invasive prenatal measurement of the fetal genome NATURE Fan, H. C., Gu, W., Wang, J., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2012; 487 (7407): 320-?

Abstract

The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.

View details for DOI 10.1038/nature11251

View details for Web of Science ID 000306506500033

View details for PubMedID 22763444

View details for PubMedCentralID PMC3561905

Computerized microfluidic cell culture using elastomeric channels and Braille displays PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Gu, W., Zhu, X. Y., Futai, N., Cho, B. S., Takayama, S. 2004; 101 (45): 15861-15866

Abstract

Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.

View details for DOI 10.1073/pnas.0404353101

View details for Web of Science ID 000225196800009

View details for PubMedID 15514025

View details for PubMedCentralID PMC528755

Cell-Free DNA Tissues-of-Origin by Methylation Profiling Reveals Significant Cell, Tissue and Organ-Specific injury related to COVID-19 Severity. Med (New York, N.Y.) Cheng, A. P., Cheng, M. P., Gu, W., Lenz, J. S., Hsu, E., Schurr, E., Bourque, G., Bourgey, M., Ritz, J., Marty, F. M., Chiu, C. Y., Vinh, D. C., De Vlaminck, I. 2021

Abstract

Background: COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19.Methods: Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls.Findings: We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cell-free DNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation.Conclusion: This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.

View details for DOI 10.1016/j.medj.2021.01.001

View details for PubMedID 33521749

CRISPR-Cas12-based detection of SARS-CoV-2. Nature biotechnology Broughton, J. P., Deng, X. n., Yu, G. n., Fasching, C. L., Servellita, V. n., Singh, J. n., Miao, X. n., Streithorst, J. A., Granados, A. n., Sotomayor-Gonzalez, A. n., Zorn, K. n., Gopez, A. n., Hsu, E. n., Gu, W. n., Miller, S. n., Pan, C. Y., Guevara, H. n., Wadford, D. A., Chen, J. S., Chiu, C. Y. 2020; 38 (7): 87074

Abstract

An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.

View details for DOI 10.1038/s41587-020-0513-4

View details for PubMedID 32300245

Evaluation of SARS-CoV-2 serology assays reveals a range of test performance. Nature biotechnology Whitman, J. D., Hiatt, J. n., Mowery, C. T., Shy, B. R., Yu, R. n., Yamamoto, T. N., Rathore, U. n., Goldgof, G. M., Whitty, C. n., Woo, J. M., Gallman, A. E., Miller, T. E., Levine, A. G., Nguyen, D. N., Bapat, S. P., Balcerek, J. n., Bylsma, S. A., Lyons, A. M., Li, S. n., Wong, A. W., Gillis-Buck, E. M., Steinhart, Z. B., Lee, Y. n., Apathy, R. n., Lipke, M. J., Smith, J. A., Zheng, T. n., Boothby, I. C., Isaza, E. n., Chan, J. n., Acenas, D. D., Lee, J. n., Macrae, T. A., Kyaw, T. S., Wu, D. n., Ng, D. L., Gu, W. n., York, V. A., Eskandarian, H. A., Callaway, P. C., Warrier, L. n., Moreno, M. E., Levan, J. n., Torres, L. n., Farrington, L. A., Loudermilk, R. P., Koshal, K. n., Zorn, K. C., Garcia-Beltran, W. F., Yang, D. n., Astudillo, M. G., Bernstein, B. E., Gelfand, J. A., Ryan, E. T., Charles, R. C., Iafrate, A. J., Lennerz, J. K., Miller, S. n., Chiu, C. Y., Stramer, S. L., Wilson, M. R., Manglik, A. n., Ye, C. J., Krogan, N. J., Anderson, M. S., Cyster, J. G., Ernst, J. D., Wu, A. H., Lynch, K. L., Bern, C. n., Hsu, P. D., Marson, A. n. 2020

Abstract

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.

View details for DOI 10.1038/s41587-020-0659-0

View details for PubMedID 32855547

Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia GENETICS IN MEDICINE Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

View details for DOI 10.1038/gim.2013.194

View details for Web of Science ID 000338601400012

Electromechanical properties of pressure-actuated poly(dimethylsiloxane) microfluidic push-down valves ANALYTICAL CHEMISTRY Chen, H., Gu, W., Cellar, N., Kennedy, R., Takayama, S., Meiners, J. 2008; 80 (15): 6110-6113

Abstract

Pressure-actuated poly(dimethylsiloxane) (PDMS) valves have been characterized with respect to their electromechanical properties. Measurements of the valve opening and closing times, threshold pressures, and impedance spectra for closed valves can be used to assess the quality of the devices in general, determine their suitability for specialized applications, such as providing electrical isolated fluidic compartments for planar patch clamping, and specify ideal operating conditions. For our particular valve designs, we report valve opening times of the order of 10-100 micros, making them suitable for rapid buffer exchange applications. They can effectively provide reversible electrical isolation between adjacent fluidic compartments with typical resistances of 5 Gohms in the closed state, which meets the gigaohm requirement for patch clamping applications.

View details for DOI 10.1021/ac800506n

View details for Web of Science ID 000258096700068

View details for PubMedID 18576665

A Microfluidic System for Rapid Bacterial Pathogen Detection 7th IEEE Conference on Nanotechnology Mai, J. D., Gaster, R. S., Wu, A., Gu, W., Mach, K. E., Liao, J. C. IEEE. 2007: 13411345

View details for Web of Science ID 000261434900301

Handheld recirculation system and customized media for microfluidic cell culture LAB ON A CHIP Futai, N., Gu, W., Song, J. W., Takayama, S. 2006; 6 (1): 149-154

Abstract

A palm-sized microfluidic recirculation system and customized media enable simplified long-term culture and imaging of cells. The combination of bare Braille display modules, a leveled monolithic surface for complete chip mounting, and a transparent heater improved portability, mechanical stability and optical accessibility. Modification of basal culture media with Leibovitz's L-15 medium enabled an incubator-free culture of carbonate-dependent cells by eliminating the need for exogenous carbon dioxide. This capability is demonstrated through time-lapse recording of proliferation of C2C12 myoblasts and MC3T3-E1 osteoblasts for over 2 weeks in ambient atmosphere without medium exchange. The method opens up new possibilities for portable cell culture and for long-term continuous visual monitoring of cells.

View details for DOI 10.1039/b510901a

View details for Web of Science ID 000235506300020

View details for PubMedID 16372083

Microscale integrated sperm sorter. Methods in molecular biology (Clifton, N.J.) Chung, Y., Zhu, X., Gu, W., Smith, G. D., Takayama, S. 2006; 321: 227-244

Abstract

This chapter describes the design and fabrication of a passively driven microfluidic sperm sorter using soft lithographic microfabrication techniques. This self-contained device can separate motile sperm from nonmotile sperm and other cellular debris. The sorting system is small (coin sized) and structurally simple. It comprises two inlets; two outlets; a sorting channel; and arrays of horizontally oriented reservoirs that function as passively driven, constant-flow-rate pumps. Sperm with higher motility are sorted out from the rest of the semen samples based on their ability to swim through interfaces between adjacent laminar streams into separate streamlines, whereas the nonmotile sperm and debris remain in their initial streamlines. The device, which we call a microscale integrated sperm sorter, does not rely on any external power sources or controllers and incorporates all sample loading and sorting functions necessary to prepare high-quality sperm for in vitro fertilization. This self-contained, inexpensive, and portable device may also be useful for developing convenient sperm motility assays that can be used at the point of care or at home.

View details for PubMedID 16508075

Computer-controlled microcirculatory support system for endothelial cell culture and shearing ANALYTICAL CHEMISTRY Song, J. W., Gu, W., Futai, N., Warner, K. A., Nor, J. E., Takayama, S. 2005; 77 (13): 3993-3999

Abstract

Endothelial cells (ECs) lining the inner lumen of blood vessels are continuously subjected to hemodynamic shear stress, which is known to modify EC morphology and biological activity. This paper describes a self-contained microcirculatory EC culture system that efficiently studies such effects of shear stress on EC alignment and elongation in vitro. The culture system is composed of elastomeric microfluidic cell shearing chambers interfaced with computer-controlled movement of piezoelectric pins on a refreshable Braille display. The flow rate is varied by design of channels that allow for movement of different volumes of fluid per variable-speed pump stroke. The integrated microfluidic valving and pumping system allowed primary EC seeding and differential shearing in multiple compartments to be performed on a single chip. The microfluidic flows caused ECs to align and elongate significantly in the direction of flow according to their exposed levels of shear stress. This microfluidic system overcomes the small flow rates and the inefficiencies of previously described microfluidic and macroscopic systems respectively to conveniently perform parallel studies of EC response to shear stress.

View details for DOI 10.1021/ac050131o

View details for Web of Science ID 000230270800033

View details for PubMedID 15987102

Microfluidics for flow cytometric analysis of cells and particles PHYSIOLOGICAL MEASUREMENT Huh, D., Gu, W., Kamotani, Y., Grotberg, J. B., Takayama, S. 2005; 26 (3): R73-R98

Abstract

This review describes recent developments in microfabricated flow cytometers and related microfluidic devices that can detect, analyze, and sort cells or particles. The high-speed analytical capabilities of flow cytometry depend on the cooperative use of microfluidics, optics and electronics. Along with the improvement of other components, replacement of conventional glass capillary-based fluidics with microfluidic sample handling systems operating in microfabricated structures enables volume- and power-efficient, inexpensive and flexible analysis of particulate samples. In this review, we present various efforts that take advantage of novel microscale flow phenomena and microfabrication techniques to build microfluidic cell analysis systems.

View details for DOI 10.1088/0967-3334/26/3/R02

View details for Web of Science ID 000229837900002

View details for PubMedID 15798290