Una O'Doherty, MD, PhD
Emeritus Professor CE of Pathology and Laboratory MedicinePerelman School of Medicine at the University of Pennsylvania
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@pennmedicine.upenn.edu
Specialty Division
Transfusion Medicine & Therapeutic 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:
Marilia Pinzone - Postdoctoral fellow
Maria Paola Bertuccio - Postdoctoral fellow
LaMont Cannon - Postdoctoral fellow
Emmanuele Venanzi-Rullo - Infectious Diesease 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
Columbia University Undergraduate Research Fellowships, 1985-1986
The Francis Smith Scholarship, 1985
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
NIAID Merit Award, 2020
Memberships and Professional Organizations
American Society for Microbiology, 2000 - present
American Association of Blood Banks, 2000 - 2011
Cell and Molecular Biology Graduate Group, 2001 - present
Penn Center for AIDS Research, 2001 - present
American Society of Hematology, 2003 - 2010
International Society for Cellular Therapy, 2003 - 2009
National Blood Foundation Grant Review Committee, 2005 - 2011
Barnard Scientific Advisory Board, 2005 - 2007
NIH NIAID Study Section Special Emphasis Panel AIDS Molecular and Cellular Biology (AMCB) with Dr. Kailash Gupta, ad hoc, 2005 - 2005
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 - 2015
Genzyme Transplant: Health Outcomes Advisory Board, 2010 - 2013
American Society for Apheresis, 2010 - present
American Society for Apheresis, Public Affairs Committee, 2010 - 2018
AIDS Policy Project, amfAR, Project Inform, Treatment Action Group
Cure-Related Clinical Research Workshop (member), 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, Targeting Latently Infected Cells without Reactivation with Dr. Robert Unfer, 2014 - 2014
NIH NIAID RFA Review Panel, Innovative Assays to Quantify HIV Latency with Dr. Raymond Schlef,, 2014 - 2014
AIDS Clinical Trials Group (ACTG) Reservoir Assays Working Group, 2015 - 2016
Zoe's Circle, Networking Event for the Women of Pathology and Laboratory Medicine, 2015 - present
NIH, NIAID Study Section for AIDS Molecular and Cellular Biology (AMCB and HCVD) with Kenneth Roebuck, 2016 - 2022
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
Scientific Advisory Board for Enterprise for Research and Advocacy to Stop and Eradicate (ERASE) HIV, Martin Delaney Collaboratory, 2021 - present
Web Links
Selected Publications
Red cell exchange for rapid leukoreduction in adults with hyperleukocytosis and leukostasis
Mack EA, Dougher MC, Ginda A, Cahill CQ, Murter M, Schell K, Tanhehco YC, Bhoj V, Fesnak AD, Siegel DL, Kambayashi T, Aqui N, O'Doherty U., Blood, 2023, PMID:38052031
Serotonin reduction in post-acute sequelae of viral infection
Wong AC, Devason AS, Umana IC, Cox TO, Dohnalová L, Litichevskiy L, Perla J, Lundgren P, Etwebi Z, Izzo LT, Kim J, Tetlak M, Descamps HC, Park SL, Wisser S, McKnight AD, Pardy RD, Kim J, Blank N, Patel S, Thum K, Mason S, Beltra JC, Michieletto MF, Ngiow SF, Miller BM, Liou MJ, Madhu B, Dmitrieva-Posocco O, Huber AS, Hewins P, Petucci C, Chu CP, Baraniecki-Zwil G, Giron LB, Baxter AE, Greenplate AR, Kearns C, Montone K, Litzky LA, Feldman M, Henao-Mejia J, Striepen B, Ramage H, Jurado KA, Wellen KE, O'Doherty U, Abdel-Mohsen M, Landay AL, Keshavarzian A, Henrich TJ, Deeks SG, Peluso MJ, Meyer NJ, Wherry EJ, Abramoff BA, Cherry S, Thaiss CA, Levy M., Cell 186(): 4851-4867, 2023, PMID:37848036
Rapid manufacturing of non-activated potent CAR T cells
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., Nat Biomed Eng, 2022, PMID:35190680
Femtomolar SARS-CoV-2 antigen aetection using the microbubbling digital assay with smartphone readout enables antigen burden quantitation and tracking
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., Clin Chem 68(): 230-239, 2021, PMID:34383886
Naive infection predicts reservoir diversity and is a formidable hurdle to HIV eradication
Pinzone MR, Weissman S, Pasternak AO, Zurakowski R, Migueles S, O'Doherty U., JCI Insight 6(): e150794, 2021, PMID:34228640
Persistence of an intact HIV reservoir in phenotypically naive T cells
Venanzi Rullo E, Pinzone MR, Cannon L, Weissman S, Ceccarelli M, Zurakowski R, Nunnari G, O'Doherty U., JCI Insight 5(): e133157, 2020, PMID:33055422
Interferon-α alters host glycosylation machinery during treated HIV infection
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, EBioMedicine 59(): doi: 10.1016/j.ebiom.2020.102945, 2020, PMID:32827942
Next-Generation sequencing in a direct model of HIV infection reveals important parallels to and differences from in vivo reservoir dynamics
Pinzone MR, Bertuccio MP, VanBelzen DJ, Zurakowski R, O'Doherty U., J Virol 94(): e01900-19, 2020, PMID:32051279
Genetic evidence that naïve T cells can contribute significantly to the HIV intact reservoir: time to re-evaluate their role".
Venanzi Rullo E, Cannon L, Pinzone MR, Ceccarelli M, Nunnari G, O'Doherty U, Clinical Infectious Diseases 69(12): 236-2237, 2019, PMID:31063189
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.
Thibodeaux SR, Tanhehco YC, Irwin L Jamensky L, Schell K, O'Doherty U, Transfusion and Apheresis Science 58(1): 100-106, 2019, PMID:30616959
