Robert W. Doms, MD, PhD
Professor of Pathology and Laboratory Medicine
Professor of Microbiology
Perelman School of Medicine at the University of Pennsylvania
Chair and Pathologist-in-Chief
Children's Hospital of Philadelphia
Contact InformationChildren’s Hospital of Philadelphia
Department of Pathology and Laboratory Medicine
Main Building, 5th Floor, Rm. 5135
34th St. & Civic Center Blvd.
Philadelphia, PA 19104
Tel: 215-590-4446
Fax: 215-590-1021
Email: domsr@email.chop.edu
Research Expertise
Research Interests:
HIV; emerging viral pathogens
Keywords:
HIV; Rift Valley fever virus; virus-host cell interactions; Andes virus
Description of Research:
Research in the Doms lab utilizes a wide array of cell biological, biochemical, genetic, and immunological techniques to study membrane proteins important in HIV/AIDS pathogenesis as well as relatively new research projects on Rift Valley Fever virus and other members of the bunyavirus family in which we seek to identify host cell pathways that are used by these viruses to infect cells.
Current projects involve the use of specific inhibitors of virus entry, many of which are now used clinically including the membrane fusion inhibitor enfuvirtide and the CCR5 antagonist maraviroc. By studying the entry process, we hope to characterize why some virus strains are more sensitive to certain classes of entry inhibitors than other virus strains and to determine if these differences correlate with virus tropism or pathogenesis. This information could also be used to help guide clinical therapy. A great deal of our work in this area involves examining viruses obtained from patients who have received these drugs, as we attempt to identify how HIV acquires resistance to entry inhibitors, and the implications this has for viral tropism. Finally, now that the structure of the HIV Env protein is better understood and the receptors with which it interacts have been identified, it is now possible to rationally modify the Env protein through genetic means in the hopes of eliciting more effective immunogens. We use both HIV-1, HIV-2 and SIV systems to address these points, comparing closely related virus strains that differ markedly in their pathogenic potential to understand how specific structural alterations can impact virus replication in vivo. Our work in this area is supported by the International AIDS Vaccine Initiative.
Over the past several years, we have initiated projects Rift Valley fever virus and several other bunyaviruses that cause disease in humans. This work is being done in collaboration with colleagues at USAMRIID at Ft. Detrick, MD as well as the Centers for Disease Control. Cell biological and genetic studies are being done at Penn, while BSL4 work is done at USAMRIID. One of our students is now a postdoctoral fellow at Ft. Detrick. We are generally interested in how these viruses interact with host cells, and in identifying host pathways that are utilized by viruses during their life cycle. Much of this work is being done in collaboration with Dr. Sara Cherry, who is an expert in applying high throughput RNAi screens to the study of different viruses.
Graduate Groups
Cell and Molecular Biology
Education
BA (Biology), Bucknell University , 1981
MD (Medicine), Yale University, 1988
PhD (Cell Biology), Yale University Ari Helenius, Thesis Advisor, 1988
Specialty Certification
American Board of Pathology, 1992
Postgraduate Training
IRTA Fellow (Advisor: Bernie Moss), NIH, 1988-89
Postdoctoral Fellow (Advisor: Ari Helenius), Yale University, 1988
Resident, Pathology, (Advisor: Bernie Moss), NIH, 1989-92
Awards and Honors
Robert P. Vidinghoff Research Scholarship, 1978-80
National Science Foundation Predoctoral Fellowship, 1981-84
Phi Beta Kappa Award, 1981
Medical Scientist Training Program, 1983
Gairman Prize for Outstanding Thesis, 1988
Paul Beeson Scholar Award, 1996
American Society for Clinical Investigation, 1997
Anderson Symposium Speaker, University of Virginia, 1998
Burroughs Wellcome Award for Translational Research, 1998
Stanley N. Cohen Biomedical Research Award, University of Pennsylvania, 1998
Elizabeth Glaser Scientist Award, Pediatric AIDS Foundation, 1999
Sidney Grossberg Lectureship, Medical College of Wisconsin, 2001
Pfizer Outstanding Investigator Award, American Society for Investigative Pathology, 2001
Plenary Speaker, 8th National Conference on Retroviruses and Opportunistic Infections, 2001
Plenary Speaker, 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris, France, 2003
Tom Matthews Memorial Lecture: 1st Inhibition of HIV Entry Workshop, 2005
Fellow, American Society for Microbiology, 2006
Association of American Physicians, 2006
Best Basic Science Lecturer, Module 1, 2007
Aaron Wyatt Memorial Lecture, University of British Columbia, 2009
President, AMSMIC (Association of Medical School Microbiology and Immunology Chairs), 2012
American Association for the Advancement of Science (AAAS), 2013
Outstanding Instruction in Microbiology (Module 1), Perelman School of Medicine at the University of Pennsylvania, 2013
MSG Basic Science Teaching Award, Medical Student Government Awards, Perelman School of Medicine at the University of Pennsylvania, 2015
Best Course Director Award for Module 1 Teaching, MS2 Pre-Clinical Teaching Awards, Perelman School of Medicine at the University of Pennsylvania, 2016, 2017
Christian R. and Mary F. Lindback Foundation Awards for Distinguished Teaching, Penn Medicine, 2018
MSG Basic Science Teaching Award, Medical Student Government Awards, Perelman School of Medicine at the University of Pennsylvania, 2020
Memberships and Professional Organizations
American Association for the Advancement of Science, 2000-present
-------- Member at Large, Section on Medical Sciences, 2008-13
-------- Fellow, 2013-present
American Society for Cell Biology
American Society for Clinical Investigation
American Society for Investigative Pathology
American Society for Microbiology
American Society for Virology
Society for Neuroscience
Selected Publications
Comparative Evaluation of Choose Your Own Adventure and Traditional Linear Case Formats in Radiology Small Group Teaching
Thomas SP, Fathy R, Aepli S, Clancy CB, Lipschik GY, Simpson SA, Katz SI, Doms RW, Nachiappan AC. Acad Radiol 29 Suppl 5:S82-S88, May 2022. doi: 10.1016/j.acra.2021.10.022. Epub 2022 Jan 2. PMID: 34987000.
What Came First-the Virus or the Egg?
Doms RW. Cell 168(5):755-757, Feb 2017. doi: 10.1016/j.cell.2017.02.012. PMID: 28235193.
Platelet Factor 4 Inhibits and Enhances HIV-1 Infection in a Concentration-Dependent Manner by Modulating Viral Attachment
Parker ZF, Rux AH, Riblett AM, Lee FH, Rauova L, Cines DB, Poncz M, Sachais BS, Doms RW. AIDS Res Hum Retroviruses 32(7):705-17, Jul 2016. doi: 10.1089/AID.2015.0344. Epub 2016 Mar 15. PMID: 26847431; PMCID: PMC4931766.
Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques
Li H, Wang S, Kong R, Ding W, Lee FH, Parker Z, Kim E, Learn GH, Hahn P, Policicchio B, Brocca-Cofano E, Deleage C, Hao X, Chuang GY, Gorman J, Gardner M, Lewis MG, Hatziioannou T, Santra S, Apetrei C, Pandrea I, Alam SM, Liao HX, Shen X, Tomaras GD, Farzan M, Chertova E, Keele BF, Estes JD, Lifson JD, Doms RW, Montefiori DC, Haynes BF, Sodroski JG, Kwong PD, Hahn BH, Shaw GM. Proc Natl Acad Sci U S A 113(24):E3413-22, Jun 2016. doi: 10.1073/pnas.1606636113. Epub 2016 May 31. PMID: 27247400; PMCID: PMC4914158.
Making Bunyaviruses Talk: Interrogation Tactics to Identify Host Factors Required for Infection
Riblett AM, Doms RW. Viruses 8(5):130, May 2016. doi: 10.3390/v8050130. PMID: 27187446; PMCID: PMC4885085.
A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection
Riblett AM, Blomen VA, Jae LT, Altamura LA, Doms RW, Brummelkamp TR, Wojcechowskyj JA. J Virol 90(3):1414-23, Nov 2015. doi: 10.1128/JVI.02055-15. PMID: 26581979; PMCID: PMC4719632.
Antibodies elicited by yeast glycoproteins recognize HIV-1 virions and potently neutralize virions with high mannose N-glycans
Zhang H, Fu H, Luallen RJ, Liu B, Lee FH, Doms RW, Geng Y. Vaccine 33(39):5140-7, Sep 2015. doi: 10.1016/j.vaccine.2015.08.012. Epub 2015 Aug 13. PMID: 26277072; PMCID: PMC4577470.
The major cellular sterol regulatory pathway is required for Andes virus infection
Petersen J, Drake MJ, Bruce EA, Riblett AM, Didigu CA, Wilen CB, Malani N, Male F, Lee FH, Bushman FD, Cherry S, Doms RW, Bates P, Briley K Jr. PLoS Pathog 10(2):e1003911, Feb 2014. doi: 10.1371/journal.ppat.1003911. PMID: 24516383; PMCID: PMC3916400.
Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection
Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Blood 123(1):61-9, Jan 2014. doi: 10.1182/blood-2013-08-521229. Epub 2013 Oct 25. PMID: 24162716; PMCID: PMC3879906.
Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry
Wojcechowskyj JA, Didigu CA, Lee JY, Parrish NF, Sinha R, Hahn BH, Bushman FD, Jensen ST, Seeholzer SH, Doms RW. Cell Host Microbe 13(5):613-623, May 2013. doi: 10.1016/j.chom.2013.04.011. PMID: 23684312; PMCID: PMC4104530.