Una O'Doherty, M.D.Ph.D.

faculty photo
Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

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

Marilia Pinzone - Postdoctoral fellow
Maria Paola Bertuccio - Postdoctoral fellow
LaMont Cannon - Postdoctoral fellow
Emmanuele Venanzi-Rullo - Infectious Diesease Fellow

Selected Publications

Ghassemi S, Durgin JS, Nunez-Cruz S, Patel J, Leferovich J, Pinzone M, Shen F, Cummins KD, Plesa G, Cantu VA, Reddy S, Bushman FD, Gill SI, O'Doherty U, O'Connor RS, Milone MC.: Rapid manufacturing of non-activated potent CAR T cells. Nat Biomed Eng 2022.

Chen H, Li Z, Feng S, Richard-Greenblatt M, Hutson E, Andrianus S, Glaser LJ, Rodino KG, Qian J, Jayaraman D, Collman RG, Glascock A, Bushman FD, Lee JS, Cherry S, Fausto A, Weiss SR, Koo H, Corby PM, Oceguera A, O'Doherty U, Garfall AL, Vogl DT, Stadtmauer EA, Wang P.: Femtomolar SARS-CoV-2 antigen aetection using the microbubbling digital assay with smartphone readout enables antigen burden quantitation and tracking. Clin Chem 68: 230-239, Aug 2021.

Pinzone MR, Weissman S, Pasternak AO, Zurakowski R, Migueles S, O'Doherty U.: Naive infection predicts reservoir diversity and is a formidable hurdle to HIV eradication. JCI Insight 6: e150794, Jul 2021.

Venanzi Rullo E, Pinzone MR, Cannon L, Weissman S, Ceccarelli M, Zurakowski R, Nunnari G, O'Doherty U.: Persistence of an intact HIV reservoir in phenotypically naive T cells. JCI Insight 5: e133157, Oct 2020.

Giron LB, Colomb F, Papasavvas E, Azzoni L, Yin X, Fair, M, Anzurez A, Damra M, Mounzer K, Kostman JR, Tebas P, O'Doherty U, Tateno H, Liu Q., Betts MR, Montaner LJ, Abdel-Mohsen M : Interferon-α alters host glycosylation machinery during treated HIV infection. EBioMedicine 59: doi: 10.1016/j.ebiom.2020.102945, August 2020.

Pinzone MR, Bertuccio MP, VanBelzen DJ, Zurakowski R, O'Doherty U.: Next-Generation sequencing in a direct model of HIV infection reveals important parallels to and differences from in vivo reservoir dynamics. J Virol 94: e01900-19, Apr 2020.

Venanzi Rullo E, Cannon L, Pinzone MR, Ceccarelli M, Nunnari G, O'Doherty U: Genetic evidence that naïve T cells can contribute significantly to the HIV intact reservoir: time to re-evaluate their role". Clinical Infectious Diseases 69(12): 236-2237, Nov 2019.

Thibodeaux SR, Tanhehco YC, Irwin L Jamensky L, Schell K, O'Doherty U: More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study. Transfusion and Apheresis Science 58(1): 100-106, Feb 2019.

Pinzone MR, VanBelzen DJ, Weissman S, Bertuccio MP, Cannon L, Venanzi-Rullo E, Migueles S, Jones RB, Mota T Joseph SB, Groen K, Pasternak AO, Hwang WT, Sherman B, Vourekas A, Nunnari G, O'Doherty U: Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion. Nature Communications 10(1): 728, 02 2019.

Steven LM, Huang K, VanBelzen DJ, Montaner LJ, O'Doherty U, Richman DD: Quantitation of integrated HIV provirus by pulsed-field gel electrophoresis and droplet digital PCR. Journal of Clinical Microbiology 56(12): pii: JCM.01158-18, Sep 2018 Notes: doi: 10.1128/JCM.01158-18. [Epub ahead of print]

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Last updated: 08/07/2023
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