PEOPLE

Una O'Doherty, MD, PhD

Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
University of Pennsylvania Perelman School of Medicine

Contact InformationDepartment of Laboratory Medicine and Therapeutic Pathology
Division of Transfusion Medicine
University of Pennsylvania
705 Stellar Chance Laboratory
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 573-7273
Fax: (215) 573-5369

Email: unao@mail.med.upenn.edu

Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

Research Expertise

Research Interests
HIV-1 latency.

Key words: HIV, latency, reservoirs, dendritic cells, viral pathogenesis, proviral integration, retrovirus, virology, T cell activation, resting T cells.

Description of Research
Highly active anti-retroviral therapy can clear the blood of HIV-1 virions. But, despite long-term suppression of virus, when the drugs are stopped the virus returns. Thus, reservoirs of latent, treatment-resistant HIV-1 exist in infected individuals and are a major barrier to cure. With the advent of ART, the challenge in the field of HIV is to clear the remaining reservoir. The challenge is significant since the reservoir is very small - less than 1 in a million CD4+ T cells are true HIV reservoir cells. Moreover, identifying the true reservoir is made more difficult because it is hidden among many defective HIV proviruses.

To better understand the challenge to cure HIV, we quantify the reservoir and to measure how much reservoir expression occurs at baseline and to what extent the reservoir visibility can be increased by stimulation. A major hurdle that we face in these studies is to distinguish replication competent HIV from defective proviruses. We believe that we have identified a technology that largely overcomes this hurdle. Our approach utilizes Fiber-optic Array Scanning Technology (or FAST) to identify rare cells that can express HIV proteins at high levels. The technique is largely based on approaches for rare cancer cell detection.

Our lab also studies HIV reservoirs by using an in vitro model that we developed and characterized. We have shown that this model mimics many important aspects of HIV in vivo. This model allows us probe the important differences between the latent and productive state of HIV infection. We are keenly interested to probe why HIV expression is less efficient in latently infected cells. This is an underexplored area that can be addresses with current sequencing and proteomic approaches.

Rotation Projects
1. Characterize the ability of FAST technology to distinguish and quantify replication competent proviruses from defective proviruses.
2. Characterize the frequency of replication competent proviruses in different patient populations.
3. Probe the mechanistic differences between latent and productive HIV Infection.


Lab personnel:

Jake VanBelzen - Postbaccalaureate student
Marilia Pinzone- Postdoctoral fellow

Itmat Expertise

HIV reservoirs, HIV immune clearance, CAR T cells

Graduate Groups

Cell and Molecular Biology

Education

B.S. (Biochemistry), Barnard College, New York, NY - cum laude, 1987
Ph.D. The Rockefeller University, New York, NY, Advisors: Drs. Nina Bhardwaj and Ralph M. Steinman, 1994
M.D. Cornell University Medical College, New York, NY, 1995

Specialty Certification

Diplomate, American Board of Pathology in Clinical Pathology, 1998

Postgraduate Training

Resident in Anatomic Pathology, Department of Pathology , New York University Medical Center, New York, NY, 1995-1996
Resident in Laboratory Medicine, Department of Pathology and Laboratory Medicine

, Hospital of the University of Pennsylvania, Philadelphia, PA, 1996-1998
Postdoctoral Research Fellow, Laboratory of Cellular Physiology and Immunology, with Dr. Melissa Pope
, The Rockefeller University, New York, NY, 1996-1996
Postdoctoral Research Fellow, Department of Microbiology, with Dr. Michael Malim, University of Pennsylvania, Philadelphia, PA, 1998-2001
Fellow in Transfusion Medicine, Department of Pathology and Laboratory Medicine , Hospital of the University of Pennsylvania, Philadelphia, PA, 2000-2001

Awards and Honors

The Francis Smith Scholarship, 1985
Columbia University Undergraduate Research Fellowships, 1985-1986
The Dr. Ann Kruttner Scholarship, 1985
Medical Scientist Training Program, Cornell-Rockefeller, 1987-1995
K08 Mentored Clinical Scientist Development Award, 1999-2004
National Blood Foundation Scholar, 2001-2002
K02 Independent Scientist Award, 2008-2013

Memberships and Professional Organizations

American Society for Microbiology, 2000 - present
American Association of Blood Banks, 2000 - present
Cell and Molecular Biology Graduate Group, 2001 - present
Penn Center for AIDS Research, 2001 - present
American Society of Hematology, 2003 - present
International Society for Cellular Therapy, 2003 - 2009
National Blood Foundation grant review committee, 2005 - 2011
NIH NIAID Study Section Special Emphasis Panel AIDS Molecular and Cellular Biology (AMCB) with Dr. Kailash Gupta, ad hoc, 2005 - 2005
Barnard Scientific Advisory Board, 2005 - 2007
AMFAR (American Foundation for AIDS Research) grant review, adhoc, 2006 - present
NIH NIAID study section AIDS Immunology and Pathogenesis (AIP) with Dr. Shiv Prasad, ad hoc, 2009 and 2015, 2009 - 2015
American Society for Apheresis, Public Affairs Committee, 2010 - present
AIDS Policy Project, amfAR, Project Inform, Treatment Action Group
Cure-Related Clinical Research Workshop, 2010 - present
American Society for Apheresis, 2010 - present
Genzyme Transplant: Health Outcomes Advisory Board, 2010 - 2013
NIH NIAID RFA review panel, Martin Delaney Program Project with Bruce Sundstrom, 2011 - 2011
NIH NIAID RFA review panel, Delivering Therapeutics to Residual Active HIV Reservoirs with Dr. Ellen Buckzo, 2013 - 2013
NIH NIAID RFA review panel, Innovative Assays to Quantify HIV latency with Dr. Raymond Schlef, April 2014, 2014 - 2014
NIH NIAID RFA review panel, Targeting latently infected cells without reactivation with Dr. Robert Unfer, 2014 - 2014
AIDS Clinical Trials Group (ACTG) Reservoir Assays Working Group, 2015 - present
NIH, NIAID study section for AIDS Molecular and Cellular Biology (AMCB) with Kenneth Roebuck, 2016 - present
NIH NIAID review panel, RFA for Precision Genome Engineering for HIV Eradication, High-Throughput Assay Platform for Quantifying Latent HIV Reservoirs, and Method for the Detection of Minority Populations of Drug Resistant HIV with Thomas Conway, 2016 - 2016

Web Links


Selected Publications

Monitoring Integration over Time Supports a Role for Cytotoxic T Lymphocytes and Ongoing Replication as Determinants of Reservoir Size.

Pinzone Marilia Rita, Graf Erin, Lynch Lindsay, McLaughlin Brigit, Hecht Frederick M, Connors Mark, Migueles Stephen A, Hwang Wei-Ting, Nunnari Giuseppe, O'Doherty Una, Journal of virology 90(23): 10436-10445, 2016, PMID:27630237

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Quantifying integrated SIV-DNA by repetitive-sampling Alu-gag PCR.

Mavigner Maud, Lee S Thera, Habib Jakob, Robinson Cameron, Silvestri Guido, O'Doherty Una, Chahroudi Ann, Journal of virus eradication 2(4): 219-226, 2016, PMID:27781104

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Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.

Lee Sulggi A, Bacchetti Peter, Chomont Nicolas, Fromentin Remi, Lewin Sharon R, O'Doherty Una, Palmer Sarah, Richman Douglas D, Siliciano Janet D, Yukl Steven A, Deeks Steven G, Burbelo Peter D, PloS one 11(8): e0160192, 2016, PMID:27483366

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Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy.

Imamichi Hiromi, Dewar Robin L, Adelsberger Joseph W, Rehm Catherine A, O'Doherty Una, Paxinos Ellen E, Fauci Anthony S, Lane H Clifford, Proceedings of the National Academy of Sciences of the United States of America 113(31): 8783-8, 2016, PMID:27432972

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A subset of CD4/CD8 double negative T cells expresses HIV proteins in patients on ART.

DeMaster Laura K, Liu Xiaohe, VanBelzen D Jake, Trinité Benjamin, Zheng Lingjie, Agosto Luis M, Migueles Stephen A, Connors Mark, Sambucetti Lidia, Levy David N, Pasternak Alexander O, O'Doherty Una, Journal of virology 90(5): 2165-79, 2015, PMID:26537682

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Minor Contribution of Host-HIV Readthrough Transcripts to the Level of HIV Cell-associated gag RNA.

Pasternak Alexander O, DeMaster Laura K, Kootstra Neeltje A, Reiss Peter, O'Doherty Una, Berkhout Ben, Journal of virology 90(2): 1148-51, 2015, PMID:26559833

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A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals.

Procopio Francesco Andrea, Fromentin Rémi, Kulpa Deanna A, Brehm Jessica H, Bebin Anne-Gaelle, Strain Matthew C, Richman Douglas D, O'Doherty Una, Palmer Sarah, Hecht Frederick M, Hoh Rebecca, Barnard Richard J O, Miller Michael D, Hazuda Daria J, Deeks Steven G, Sékaly Rafick-Pierre, Chomont Nicolas, EBioMedicine 2(8): 872-81, 2015, PMID:26425694

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CD4+ and CD8+ T Cell Activation Are Associated with HIV DNA in Resting CD4+ T Cells.

Cockerham Leslie R, Siliciano Janet D, Sinclair Elizabeth, O'Doherty Una, Palmer Sarah, Yukl Steven A, Strain Matt C, Chomont Nicolas, Hecht Frederick M, Siliciano Robert F, Richman Douglas D, Deeks Steven G, PloS one 9(10): e110731, 2014, PMID:25340755

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Association between mobilization regimen and PFS after auto-SCT for multiple myeloma.

Garfall A L, Dougherty A L, Vogl D T, Weiss B M, Cohen A D, Mick R, O'Doherty U, Stadtmauer E A, Bone marrow transplantation 49(11): 1439-41, 2014, PMID:25046220

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Quantification of integrated HIV DNA by repetitive-sampling Alu-HIV PCR on the basis of poisson statistics.

De Spiegelaere Ward, Malatinkova Eva, Lynch Lindsay, Van Nieuwerburgh Filip, Messiaen Peter, O'Doherty Una, Vandekerckhove Linos, Clinical chemistry 60(6): 886-95, 2014, PMID:24664400

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