Dr Daniel S Chen, MD PhD - IGM Biosciences - Chief Medical Officer

Dr Daniel S Chen

MD PhD

IGM Biosciences

Chief Medical Officer

Mountain View, CA | United States

Main Specialties: Oncology

Additional Specialties: Immunology, Oncology, Melanoma, Biomarkers, Clinical Development, Cancer Immunotherapy

ORCID logohttps://orcid.org/0000-0001-5085-3579

Dr Daniel S Chen, MD PhD - IGM Biosciences - Chief Medical Officer

Dr Daniel S Chen

MD PhD

Introduction

Primary Affiliation: IGM Biosciences - Mountain View, CA , United States

Specialties:

Additional Specialties:

Research Interests:

Education

Aug 2018
IGM Biosciences

Chief Medical Officer
Jul 2018
Genentech/Roche

VP Global Head of Cancer Immunotherapy
Feb 2006
Stanford Cancer Center

Running Metastatic Melanoma Clinic
Jun 2004
Stanford University
Immunology Post-doctorate
with Mark Davis, PhD
Jun 2003
Stanford Cancer Center
Medical Oncology Fellowship
Jun 1998 - May 2003
Stanford Hospital and Clinics
Internal Medicine Internship, Internal Medicine Residency, Medical Oncology Fellowship
Medicine, Medical Oncology
Jun 2000
Stanford University
Internal Medicine Residency
Sep 1990 - May 1998
University of Southern California Department of Medicine
MD PhD
Medicine, Microbiology & Immunology
May 1998
University of Southern California Medical School
M.D. PhD Microbiology and Immunology
Sep 1986 - May 1990
Massachusetts Institute of Technology
B.S.

Experience

Mar 2009 - Jul 2018
Roche
VP, Global Head of Cancer Immunotherapy
Development
Feb 2006 - Jul 2018
Genentech
VP, Global Head of Cancer Immunotherapy
Development
Feb 2017
co-author "Elements of cancer immunity: the cancer immune set point"
Author
Chen and Mellman, Nature, 2017
Jun 2003 - Aug 2016
Stanford University
MD PhD, Melanoma, Cutaneous Oncology
Medical Oncology, Microbiology & Immunology, Howard Hughes Medical Institute, Stanford Cancer Center
Nov 2014
Keynote Presentation: AACR EORTC NCI Targeted Therapies Annual Meeting
Presenter
Cancer Immunotherapy and the T cell Army
Jul 2013
co-author "Oncology meets Immunology: the Cancer-Immunity Cycle"
Author
Chen and Mellman, Immunology, 2013
Aug 2018
IGM Biosciences
Chief Medical Officer

Publications

55Publications

3029Reads

63Profile Views

3326PubMed Central Citations

Combinations of Bevacizumab With Cancer Immunotherapy.

Cancer J 2018 Jul/Aug;24(4):193-204

From Genentech, Inc., South San Francisco, CA.

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http://Insights.ovid.com/crossref?an=00130404-201807000-0000
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http://dx.doi.org/10.1097/PPO.0000000000000327DOI Listing
June 2019
35 Reads
4.240 Impact Factor

Introduction by the Guest Editors: Bevacizumab.

Cancer J 2018 Jul/Aug;24(4):163-164

Genentech, Inc, South San Francico, CA.

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http://dx.doi.org/10.1097/PPO.0000000000000325DOI Listing
June 2019
5 Reads
4.240 Impact Factor

VEGF in Signaling and Disease: Beyond Discovery and Development.

Cell 2019 Mar;176(6):1248-1264

Department of Pathology, University of California, San Diego, CA, USA; Department of Ophthalmology, University of California, San Diego, CA, USA; The Moores Cancer Center, University of California, San Diego, CA, USA.

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https://linkinghub.elsevier.com/retrieve/pii/S00928674193005
Publisher Site
http://dx.doi.org/10.1016/j.cell.2019.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410740PMC
March 2019
9 Reads
32.242 Impact Factor

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8 + T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8 + T cells from the tumour parenchyma that were instead found in the fibroblast-and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-Administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-Tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-Tumour immunity by restricting T-cell infiltration.

http://lup.lub.lu.se/record/eafb86a6-8810-4b93-8882-732363b8ff58

View Article
2018
1 Read

TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Therapeutic antibodies that block the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer (mUC)1–5. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here, we examined tumours from a large cohort of mUC patients treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). Lack of response was associated with a signature of transforming growth factor β (TGF-β) signalling in fibroblasts, particularly in patients with CD8+ T cells that were excluded from the tumour parenchyma and instead found in the fibroblast- and collagen-rich peritumoural stroma—a common phenotype among patients with mUC. Using a mouse model that recapitulates this immune excluded phenotype, we found that therapeutic administration of a TGF-β blocking antibody together with anti–PD-L1 reduced TGF-β signalling in stromal cells, facilitated T cell penetration into the centre of the tumour, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding outcome in this setting and suggests that TGF-β shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T cell infiltration.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028240/

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2018
1 Read

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement

Journal of Clinical Oncology

Tsimberidou AM, Levit LA, Schilsky RL, Averbuch SD, Chen DS, Kirkwood JM, McShane LM, Sharon E, Mileham KF, Postow MA. Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement. J Clin Oncol. 2018 Oct 19:JCO1800145. doi: 10.1200/JCO.18.00145; simultaneous publication in J Immunother Cancer. 2018 Oct 19;6(1):108. doi: 10.1186/s40425-018-0426-7

http://ascopubs.org/doi/abs/10.1200/JCO.18.00145

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October 2018

Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy.

J Clin Oncol 2018 03 17;36(9):850-858. Epub 2018 Jan 17.

F. Stephen Hodi and Mizuki Nishino, Dana-Farber Cancer Institute, Boston, MA; Marcus Ballinger, Benjamin Lyons, Chris McKenna, Ina Rhee, Gregg Fine, Nathan Winslow, and Daniel S. Chen, Genentech, South San Francisco, CA; Jean-Charles Soria, AstraZeneca, Gaithersburg, MD; Josep Tabernero, Universitat Autònoma de Barcelona, Barcelona, Spain; Thomas Powles, Queen Mary University of London, London, United Kingdom; David Smith, Compass Oncology, Vancouver, WA; Axel Hoos, GlaxoSmithKline, Collegeville, PA; Ulrich Beyer, Roche Innovation Center, Basel, Switzerland; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.

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http://dx.doi.org/10.1200/JCO.2017.75.1644DOI Listing
March 2018
83 Reads
8 Citations
18.430 Impact Factor

Elements of cancer immunity and the cancer-immune set point.

Nature 2017 01;541(7637):321-330

Genentech, 1 DNA Way, South San Francisco, California 94080, USA.

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http://www.nature.com/articles/nature21349
Publisher Site
http://dx.doi.org/10.1038/nature21349DOI Listing
January 2017
72 Reads
152 Citations
42.351 Impact Factor

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial

Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population. ; status: published

https://lirias.kuleuven.be/handle/123456789/536990

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2016
1 Read

Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma

Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8+ T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8+ T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013615/

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2016
2 Reads

Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure).

Authors:
J M Kim D S Chen

Ann Oncol 2016 08 20;27(8):1492-504. Epub 2016 May 20.

Genentech, South San Francisco Stanford Medical Oncology, Stanford University School of Medicine, Stanford, USA

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http://dx.doi.org/10.1093/annonc/mdw217DOI Listing
August 2016
62 Reads
22 Citations
7.040 Impact Factor

MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer.

Nature 2014 Nov;515(7528):558-62

University of Nevada School of Medicine and US Oncology/Comprehensive Cancer Centers of Nevada, 3730 S. Eastern Avenue, Las Vegas, Nevada 89169, USA.

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http://dx.doi.org/10.1038/nature13904DOI Listing
November 2014
187 Reads
488 Citations
42.351 Impact Factor

Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy

Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix–associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL7 antibodies inhibited both of these key processes and augmented anti-VEGF–mediated vascular damage in various murine tumor models. In a genetically engineered mouse model of advanced non–small cell lung cancer, we found that anti-EGFL7 enhanced both the progression-free and overall survival benefits derived from anti-VEGF therapy in a dose-dependent manner. In addition, we identified a circulating progenitor cell type that was regulated by EGFL7 and evaluated the response of these cells to anti-EGFL7 treatment in both tumor-bearing mice and cancer patients from a phase I clinical trial. Importantly, these preclinical efficacy and clinical biomarker results enabled rational selection of the anti-EGFL7 dose currently being tested in phase II clinical trials.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754254

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2013

Oncology meets immunology: the cancer-immunity cycle.

Immunity 2013 Jul;39(1):1-10

Stanford Medical Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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http://dx.doi.org/10.1016/j.immuni.2013.07.012DOI Listing
July 2013
89 Reads
440 Citations
21.561 Impact Factor

Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab.

Clin Cancer Res 2013 Feb 20;19(4):929-37. Epub 2012 Nov 20.

Department of Oncology Biomarkers, Genentech, Inc., South San Francisco, CA 94080, USA.

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http://dx.doi.org/10.1158/1078-0432.CCR-12-2535DOI Listing
February 2013
7 Reads
50 Citations
8.722 Impact Factor

A Systemic Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy

BACKGROUND: Melanoma is a relatively immunogenic tumor, in which infiltration of melanoma cells by T lymphocytes is associated with a better clinical prognosis. We hypothesized that radiation-induced cell death may provide additional stimulation of an anti-tumor immune response in the setting of anti-CTLA-4 treatment. METHODS: In a pilot melanoma patient, we prospectively tested this hypothesis. We treated the patient with two cycles of ipilimumab, followed by stereotactic ablative radiotherapy to two of seven hepatic metastases, and two additional cycles of ipilimumab. RESULTS: Subsequent positron emission tomography-computed tomography scan indicated that all metastases, including unirradiated liver lesions and an unirradiated axillary lesion, had completely resolved, consistent with a complete response by RECIST. CONCLUSION: The use of radiotherapy in combination with targeted immunotherapy as a noninvasive in vivo tumor vaccine strategy appears to be a promising method of enhancing the induction of systemic immune responses and anti-tumor effect.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542835

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2012
1 Read

Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1.

Clin Cancer Res 2012 Dec 19;18(24):6580-7. Epub 2012 Oct 19.

Stanford Medical Oncology, Stanford, California, USA.

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http://dx.doi.org/10.1158/1078-0432.CCR-12-1362DOI Listing
December 2012
18 Reads
95 Citations
8.722 Impact Factor

A systemic complete response of metastatic melanoma to local radiation and immunotherapy.

Transl Oncol 2012 Dec 1;5(6):404-7. Epub 2012 Dec 1.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542835PMC
http://dx.doi.org/10.1593/tlo.12280DOI Listing
December 2012
20 Reads
61 Citations

Abscopal effect in a patient with melanoma.

N Engl J Med 2012 05;366(21):2035; author reply 2035-6

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http://dx.doi.org/10.1056/NEJMc1203984DOI Listing
May 2012
18 Reads
30 Citations
55.873 Impact Factor

Impact of exploratory biomarkers on the treatment effect of bevacizumab in metastatic breast cancer.

Clin Cancer Res 2011 Jan 11;17(2):372-81. Epub 2011 Jan 11.

Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom.

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http://dx.doi.org/10.1158/1078-0432.CCR-10-1791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023787PMC
January 2011
48 Reads
33 Citations
8.722 Impact Factor

Molecular biomarker analyses using circulating tumor cells.

PLoS One 2010 Sep 8;5(9):e12517. Epub 2010 Sep 8.

Department of Oncology Biomarker Development, Genentech, Inc, South San Francisco, California, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012517PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935889PMC
September 2010
20 Reads
92 Citations
3.234 Impact Factor

T cells use two directionally distinct pathways for cytokine secretion.

Nat Immunol 2006 Mar 29;7(3):247-55. Epub 2006 Jan 29.

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.

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http://dx.doi.org/10.1038/ni1304DOI Listing
March 2006
9 Reads
147 Citations
20.004 Impact Factor

Molecular and functional analysis using live cell microarrays.

Curr Opin Chem Biol 2006 Feb 18;10(1):28-34. Epub 2006 Jan 18.

Department of Microbiology and Immunology and the Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

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http://dx.doi.org/10.1016/j.cbpa.2006.01.001DOI Listing
February 2006
4 Reads
22 Citations
6.813 Impact Factor

Marked differences in human melanoma antigen-specific T cell responsiveness after vaccination using a functional microarray.

PLoS Med 2005 Oct 20;2(10):e265. Epub 2005 Sep 20.

Department of Internal Medicine/Division of Oncology, Stanford University, Stanford, California, United States of America.

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http://dx.doi.org/10.1371/journal.pmed.0020265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216330PMC
October 2005
17 Reads
34 Citations

Cellular immunotherapy: antigen recognition is just the beginning.

Springer Semin Immunopathol 2005 Jun 16;27(1):119-27. Epub 2005 Apr 16.

Department of Internal Medicine, Division of Oncology, Stanford University, Stanford, California 94305-5124, USA.

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http://dx.doi.org/10.1007/s00281-005-0200-zDOI Listing
June 2005
6 Reads
6 Citations

Detection and characterization of cellular immune responses using peptide-MHC microarrays.

The detection and characterization of antigen-specific T cell populations is critical for understanding the development and physiology of the immune system and its responses in health and disease. We have developed and tested a method that uses arrays of peptide-MHC complexes for the rapid identification, isolation, activation, and characterization of multiple antigen-specific populations of T cells. CD4(+) or CD8(+) lymphocytes can be captured in accordance with their ligand specificity using an array of peptide-MHC complexes printed on a film-coated glass surface. We have characterized the specificity and sensitivity of a peptide-MHC array using labeled lymphocytes from T cell receptor transgenic mice. In addition, we were able to use the array to detect a rare population of antigen-specific T cells following vaccination of a normal mouse. This approach should be useful for epitope discovery, as well as for characterization and analysis of multiple epitope-specific T cell populations during immune responses associated with viral and bacterial infection, cancer, autoimmunity, and vaccination.

https://doi.org/10.1371/journal.pbio.0000065

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2003

Detection and characterization of cellular immune responses using peptide-MHC microarrays.

PLoS Biol 2003 Dec 22;1(3):E65. Epub 2003 Dec 22.

Department of Biochemistry, Stanford University, Stanford, California, USA.

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http://dx.doi.org/10.1371/journal.pbio.0000065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC300678PMC
December 2003
6 Reads
38 Citations

Mouse hepatitis virus infection induces an early, transient calcium influx in mouse astrocytoma cells.

Exp Cell Res 1997 Nov;237(1):55-62

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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http://dx.doi.org/10.1006/excr.1997.3768DOI Listing
November 1997
3 Reads
3.250 Impact Factor

Retroviral vector-mediated transfer of an antisense cyclin G1 construct inhibits osteosarcoma tumor growth in nude mice.

Hum Gene Ther 1997 Sep;8(14):1667-74

Department of Microbiology, Childrens Hospital of Los Angeles Research Institute, and the University of Southern California School of Medicine 90033, USA.

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http://dx.doi.org/10.1089/hum.1997.8.14-1667DOI Listing
September 1997
3 Reads
6 Citations
3.755 Impact Factor

Human carcinoembryonic antigen and biliary glycoprotein can serve as mouse hepatitis virus receptors.

J Virol 1997 Feb;71(2):1688-91

Howard Hughes Medical Institute, University of Southern California School of Medicine, Los Angeles 90033-1054, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC191232PMC
February 1997
2 Reads
11 Citations
4.440 Impact Factor

A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.

Proc Natl Acad Sci U S A 1995 Dec;92(26):12095-9

Howard Hughes Medical Institute, School of Medicine, University of Southern California, Los Angeles 90033-1054, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC40303PMC
http://dx.doi.org/10.1073/pnas.92.26.12095DOI Listing
December 1995
3 Reads
30 Citations
9.810 Impact Factor

Top co-authors

Priti S Hegde
Priti S Hegde

Collegeville

9
Ira Mellman
Ira Mellman

Yale University School of Medicine

6
Mark M Davis
Mark M Davis

Stanford University School of Medicine

5
Gregg D Fine
Gregg D Fine

Genentech

5
Hartmut Koeppen
Hartmut Koeppen

The University of Texas M. D. Anderson Cancer Center

5
Thomas Powles
Thomas Powles

St Bartholomew's Hospital

5
David F McDermott
David F McDermott

Harvard Medical School

4
Marcus Ballinger
Marcus Ballinger

Genentech

4
Marcin Kowanetz
Marcin Kowanetz

Ludwig Institute for Cancer Research

4
Adrian M Jubb
Adrian M Jubb

University of Oxford

3