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Una O'Doherty, MD, PhD

Una O'Doherty, MD, PhD Physician

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

Dr. O'Doherty is a Penn Medicine employed physician.

Clinical Specialties

Specialty:

  • Pathology and Laboratory Medicine

Programs & Centers:

  • Cancer
    • Bone Marrow Transplant and Stem Cell Transplant Program
    • Hematological Malignancies (Blood Cancer) Program
  • Pathology and Laboratory Medicine
    • Immunobiology and Experimental Pathology
    • Transfusion Medicine and Therapeutic Pathology

Board Certification:

  • Pathology - Clinical Pathology, 1998

Clinical Expertise:

  • Blood Cancer
  • Bone Marrow Diseases
  • Bone Marrow Transplant
  • Cancer Screening and Diagnostics

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Cigna HealthSpring
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • PA Medicare
  • Preferred Care
  • Rail Road Medicare / Palmetto GBA
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: NewYork-Presbyterian/Weill Cornell Medical Center
Residency: New York University
Residency: Hospital of the University of Pennsylvania
Fellowship: Hospital of the University of Pennsylvania

Memberships

AIDS Clinical Trials Group (ACTG) Reservoir Assays Working Group, National AIDS Policy Project, amfAR, Project Inform, Treatment Action Group Cure-Related Clinical Research Workshop, International American Association of Blood Banks, National American Society for Apheresis, National American Society for Apheresis, Public Affairs Committee, National American Society for Microbiology, National American Society of Hematology, National AMFAR (American Foundation for AIDS Research) grant review, adhoc, National Cell and Molecular Biology Graduate Group, Local 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, National Penn Center for AIDS Research, Local

Hospital Affiliation

Dr. O'Doherty is a Penn Medicine employed physician.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.
  • Penn Presbyterian Medical Center: Has privileges to treat patients in the hospital.
  • Pennsylvania Hospital: Has privileges to treat patients in the hospital.

Research

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. Our lab has developed an in vitro model of HIV-1 latency. We use quantitative and imaging methods to study how HIV-1 establishes latent infection in resting CD4+ T cells.

Current dogma holds that latent HIV-1 infection occurs only when T cells are activated. Our findings challenge this. Using novel quantitative assays we made three discoveries about latent HIV-1 infection in CD4+ T cells. One, HIV-1 can integrate into resting CD4+ T cells. Two, the T cells bearing integrated HIV-1 genomes do not produce new virions unless stimulated. Three after stimulation a percentage of these cells produce virus. Thus, in our system HIV-1 establishes latent infection in resting T cells in the absence of activating stimuli. We now want to determine if reservoirs form more efficiently in the presence of subtle stimuli and if reservoirs form preferentially in subsets of resting T cells that are more permissive for HIV-1 integration. We are attempting to quantify the contribution of memory and naive cells to reservoirs in vivo. Finally, we are interested to determine how reservoirs are maintained in vivo. To study this, we are first developing assays that can sensitively detect ongoing replication.

In addition, a new focus in our lab is to enhance transduction of resting CD4+ T cells with gene therapy vectors based on the HIV genome.

In summary, we have developed an in vitro model of HIV-1 latency and our studies promise to provide new insights into reservoir formation in HIV-1 infected individuals and may eventually lead to novel therapies.

Rotation Projects
1. Measure the percentage of resting T cells that contain provirus (integrated viral DNA) in HIV-infected individuals in various CD4+ T cell subpopulations including memory and naïve subsets to understand the contribution of both of these cell types to reservoirs.
2. Measure total, linear and integrated HIV DNA to determine if ongoing replication occurs on HAART.
3. Quantify the frequency of multiply infected cells after single round infection of resting CD4+ T cells to determine if hypersusceptible cells exist among naive and memory cells.
4. Determine the susceptibilities of other primary WBC (dendritic cells and progenitor cells to HIV integration).

Lab personnel:

Jenny Yu - Research Specialist
Angela Mexas - Postdoctoral fellow

Selected Publications:

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: CD4+ and CD8+ T Cell Activation Are Associated with HIV DNA in Resting CD4+ T Cells. PloS one 9 (10): e110731,2014.

Garfall A L, Dougherty A L, Vogl D T, Weiss B M, Cohen A D, Mick R, O'Doherty U, Stadtmauer E A: Association between mobilization regimen and PFS after auto-SCT for multiple myeloma. Bone marrow transplantation 49 (11): 1439-41,2014.

De Spiegelaere Ward, Malatinkova Eva, Lynch Lindsay, Van Nieuwerburgh Filip, Messiaen Peter, O'Doherty Una, Vandekerckhove Linos: Quantification of integrated HIV DNA by repetitive-sampling Alu-HIV PCR on the basis of poisson statistics. Clinical chemistry 60 (6): 886-95,2014.

Pace Matthew J, Graf Erin H, O'Doherty Una: HIV 2-long terminal repeat circular DNA is stable in primary CD4+T Cells. Virology 441 (1): 18-21,2013.

Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, Lysenko ES, Bosch RJ, Lai J, Chioma S, Emad F, Abdel-Mohsen M, Hoh R, Hecht F, Hunt P, Somsouk M, Wong J, Johnston R, Siliciano RF, Richman DD, O'Doherty U, Palmer S, Deeks SG, Siliciano JD: Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies. PLoS pathogens 9 (2): e1003174,2013.

Brady T, Kelly BJ, Male F, Roth S, Bailey Aubrey, Malani N, Gijsbers R, O'Doherty U, Bushman FD: Quantitation of HIV DNA integration: Effects of differential integration site distributions on Alu-PCR assays. Journal of virological methods 189 (1): 53-57,2013.

Azzoni Livio, Foulkes Andrea S, Papasavvas Emmanouil, Mexas Angela M, Lynn Kenneth M, Mounzer Karam, Tebas Pablo, Jacobson Jeffrey M, Frank Ian, Busch Michael P, Deeks Steven G, Carrington Mary, O'Doherty Una, Kostman Jay, Montaner Luis J: Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. The Journal of infectious diseases 207 (2): 213-22,2013.

View all publications

Academic Contact Info

Department of Laboratory Medicine and Therapeutic Pathology
Division of Transfusion Medicine
University of Pennsylvania
705 Stellar Chance Laboratory
422 Curie Blvd.

Philadelphia, PA 19104
Phone: (215) 573-7273
Fax: (215) 573-5369

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