Division of Hematology/Oncology

Faculty

faculty photo

Beatrice H. Hahn, M.D.

Professor of Medicine
Department: Medicine

Contact information
Perelman School of Medicine
University of Pennsylvania
409 Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
Office: 215-746-8515
Fax: 215-573-8976
Lab: 215-573-7663
Graduate Group Affiliations
Education:
M.D.
University of Munich, Medical School, Munich, Germany, 1981.
Doctorate (Medicine)
University of Munich, Medical School, Munich, Germany, 1982.
Post-Graduate Training
Postdoctoral Fellow, National Cancer Institute, Bethesda, MD, 1982-1985.
Postdoctoral Fellow, National Institutes of Health, Laboratory of Tumor Cell Biology, Bethesda, MD, 1982-1985.
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Description of Research Expertise

My laboratory has had a long-standing interest in elucidating the origins and evolution of human and simian immunodeficiency viruses, and in studying HIV/SIV gene function and disease mechanisms from an evolutionary perspective. Characterizing the evolutionary relationships of simian immunodeficiency viruses infecting different non-human primate species in sub-Saharan Africa, we found that Acquired Immunodeficiency Syndrome (AIDS) – one of the most devastating infectious diseases to have emerged in recent history – was the result of cross-species infections of humans by lentiviruses of primate origin. Specifically, we discovered that HIV-1 resulted from cross-species infections of SIVcpz and SIVgor naturally infecting chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla), respectively, while HIV-2 resulted from transmissions of SIVsmm infecting sooty mangabeys (Cercocebus atys). Moreover, we found that these viruses had entered the human population on multiple occasions, although only one of these transfers had spawned the HIV-1 pandemic. As we now know from molecular clock analyses, the main group of HIV-1, which has afflicted more than 70 million people and caused more than 30 million deaths worldwide, was transmitted to humans in the first third of the 20th century.

To further characterize the primate reservoirs of HIV-1 and HIV-2, we developed non-invasive methods of SIV detection and characterization. These novel (urine and fecal based) methods allowed us to pinpoint the geographic origin of epidemic HIV-2, trace the source of pandemic (group M) and non-pandemic (group N) HIV-1 to geographically isolated chimpanzee communities in southern Cameroon, and discover in wild gorilla populations viruses closely related to HIV-1 group O. We also performed the first natural history study of SIVcpz in Gombe National Park, determining the prevalence, transmission patterns and pathogenicity of this virus in both habituated and non-habituated chimpanzee communities. Combining virological, ecological, behavioral and necropsy data from over a decade, we found that SIVcpz, like HIV-1, causes significantly increased mortality and AIDS-like immunopathology in wild chimpanzees. We also found that in at least one instance high SIVcpz prevalence rates contributed to the decline of a chimpanzee community. This was a surprising finding, since until then it had been assumed for a long time that SIVcpz was non-pathogenic in its natural host.

Most recently, we have employed our non-invasive detection methods to determine the origin of the human malaria parasite Plasmodium falciparum. Screening ~3,000 ape fecal samples from 60 field sites in central Africa, we found Plasmodium spp. infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape Plasmodium infections were highly prevalent, widely distributed, and almost always comprised of mixed parasite species. Phylogenetic analyses of full-length Plasmodium mitochondrial sequences revealed that human P. falciparum is of gorilla origin, and not as previously reported of chimpanzee, bonobo or ancient human origin. Moreover, just like for HIV-1, we found that pandemic P. falciparum had resulted from a single cross-species transmission event.
In the future, we will continue to work on emerging infectious diseases and build basic and translational research programs in global health. Current projects involve:

1. Studies of HIV-1 transmission. We have devised a way to infer the nucleotide sequence of HIV-1 strains that are responsible for initiating productive infection. We are interested in determining whether these transmitted/founder viruses have unique biological properties that render them uniquely suited for mucosal transmission.

2. Studies of ape Plasmodium infections. We will investigate whether African apes represent a recurrent source of human infection by characterizing potential ape reservoirs and using 454 sequencing to detect ape Plasmodium in humans at risk for such infections.

3. Studies of SIVcpz infection of wild chimpanzees. We are interested in the impact of SIVcpz infection on chimpanzee population dynamics and will continue our natural history studies in Gombe National Park and other sites in Tanzania.

4. Studies in HIV vaccine development. We are interested in examining new platforms for HIV immunogen design and delivery.

Members of the Hahn Lab

Current members of the Hahn lab, with the month and the year they joined the lab, their previous institution, and a brief description of their projects (updated summer 2011):

Research Assistant Professors:
Weimin Liu, M.D.
(06/02) Plasmodium infections of wild apes
Yingying Li, M.D. (06/97) Molecular epidemiology of SIVcpz in wild-living chimpanzees

Research Associate:
Gerald H. Learn, Ph.D.
(03/08) Molecular evolution of HIV/SIV and ape Plasmodium infections

Laboratory Supervisor:
Erica L.H. Parrish
(10/10)

Students:
Nicholas F. Parrish
(8/09) B.S., Emory University. Biological phenotype of transmitted founder HIV-1
Shilpa S. Iyer (8/10) B.S., Fergusson College, M.S. University of Pune, Pune, India. Fitness costs associated with HIV-1 immune escape
Sesh Sundararaman (3/11) B.S., Williams College. Great ape reservoirs of human malaria.

Technicians:
Miguel Ramirez
(08/11)
Andrew G. Smith (07/11)

Former postdocs:
Lilly Kong, D.V.M.
, Chief Scientific Officer, PrimeraDx
Scott Michael, Ph.D., Associate Professor, Florida Gulf Coast University
John Kappes, Ph.D., Associate Professor, University of Alabama
Feng Gao, M.D., Professor, Duke University
Thomas Fletcher, Ph.D., Chief Scientific Officer, Immugen Pharmaceuticals, Inc.
Sundarasamy Mahalingam, Ph.D., Associate Professor, Indian Institute of Technology Madras, India
David Robertson, Ph.D., Senior Lecturer, University of Manchester, United Kingdom
Brandon Keele, Ph.D., Senior Scientist SAIC-Frederick, NCI-Frederick

Former students:
Yuexia Li, Ph.D.
, Senior Director of Quality Systems, Tetracore, Inc
Stanley Trask, M.S., Research Scientist, Affymetix
Marcelo Soares, Ph.D., Professor of Genetics, Universidade Federal do Rio de Janeiro, Brazil
Mario L. Santiago, Ph.D., Assistant Professor, University of Colorado
Rebecca Rudicell, Ph.D., Postdoctoral Fellow, Vaccine Research Center, NIH

Selected Publications

Gogarten Jan F, Akoua-Koffi Chantal, Calvignac-Spencer Sebastien, Leendertz Siv Aina J, Weiss Sabrina, Couacy-Hymann Emmanuel, Koné Inza, Peeters Martine, Wittig Roman M, Boesch Christophe, Hahn Beatrice H, Leendertz Fabian H: The ecology of primate retroviruses - An assessment of 12 years of retroviral studies in the Taï national park area, Côte d׳Ivoire. Virology 460-461C: 147-153, Jul 2014.

Abkallo Hussein M, Liu Weimin, Hokama Sarina, Ferreira Pedro E, Nakazawa Shusuke, Maeno Yoshimasa, Quang Nguyen T, Kobayashi Nobuyuki, Kaneko Osamu, Huffman Michael A, Kawai Satoru, Marchand Ron P, Carter Richard, Hahn Beatrice H, Culleton Richard: DNA from pre-erythrocytic stage malaria parasites is detectable by PCR in the faeces and blood of hosts. International Journal for Parasitology 44(7): 467-73, Apr 2014.

Veillette Maxime, Désormeaux Anik, Medjahed Halima, Gharsallah Nour-Elhouda, Coutu Mathieu, Baalwa Joshua, Guan Yongjun, Lewis George, Ferrari Guido, Hahn Beatrice H, Haynes Barton F, Robinson James E, Kaufmann Daniel E, Bonsignori Mattia, Sodroski Joseph, Finzi Andrés: Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. Journal of Virology 88(5): 2633-44, Mar 2014.

Liu Weimin, Li Yingying, Shaw Katharina S, Learn Gerald H, Plenderleith Lindsey J, Malenke Jordan A, Sundararaman Sesh A, Ramirez Miguel A, Crystal Patricia A, Smith Andrew G, Bibollet-Ruche Frederic, Ayouba Ahidjo, Locatelli Sabrina, Esteban Amandine, Mouacha Fatima, Guichet Emilande, Butel Christelle, Ahuka-Mundeke Steve, Inogwabini Bila-Isia, Ndjango Jean-Bosco N, Speede Sheri, Sanz Crickette M, Morgan David B, Gonder Mary K, Kranzusch Philip J, Walsh Peter D, Georgiev Alexander V, Muller Martin N, Piel Alex K, Stewart Fiona A, Wilson Michael L, Pusey Anne E, Cui Liwang, Wang Zenglei, Färnert Anna, Sutherland Colin J, Nolder Debbie, Hart John A, Hart Terese B, Bertolani Paco, Gillis Amethyst, LeBreton Matthew, Tafon Babila, Kiyang John, Djoko Cyrille F, Schneider Bradley S, Wolfe Nathan D, Mpoudi-Ngole Eitel, Delaporte Eric, Carter Richard, Culleton Richard L, Shaw George M, Rayner Julian C, Peeters Martine, Hahn Beatrice H, Sharp Paul M: African origin of the malaria parasite Plasmodium vivax. Nature Communications 5: 3346, 2014.

Wanaguru Madushi, Liu Weimin, Hahn Beatrice H, Rayner Julian C, Wright Gavin J: RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 110(51): 20735-40, Dec 2013.

Schmökel Jan, Li Hui, Shabir Asma, Yu Hangxing, Geyer Matthias, Silvestri Guido, Sodora Donald L, Hahn Beatrice H, Kirchhoff Frank: Link between primate lentiviral coreceptor usage and Nef function. Cell reports 5(4): 997-1009, Nov 2013.

Moeller Andrew H, Shilts Meghan, Li Yingying, Rudicell Rebecca S, Lonsdorf Elizabeth V, Pusey Anne E, Wilson Michael L, Hahn Beatrice H, Ochman Howard: SIV-Induced Instability of the Chimpanzee Gut Microbiome. Cell Host & Microbe 14(3): 340-5, Sep 2013.

Ayouba Ahidjo, Akoua-Koffi Chantal, Calvignac-Spencer Sébastien, Esteban Amandine, Locatelli Sabrina, Li Hui, Li Yingying, Hahn Beatrice H, Delaporte Eric, Leendertz Fabian H, Peeters Martine: Evidence for continuing cross-species transmission of SIVsmm to humans: characterization of a new HIV-2 lineage in rural Côte d'Ivoire. AIDS (London, England) 27(15): 2488-91, Sep 2013.

Li Hui, Blair Lily, Chen Yalu, Learn Gerald, Pfafferott Katja, John Mina, Bhattacharya Tanmoy, Hahn Beatrice H, Mallal Simon, Shaw George M, Bar Katharine J: Molecular Mechanisms of HIV-1 Prophylaxis Failure Revealed by Single Genome Sequencing. The Journal of Infectious Diseases 208(10): 1598-603, Sep 2013.

Letko Michael, Silvestri Guido, Hahn Beatrice H, Bibollet-Ruche Frederick, Gokcumen Omer, Simon Viviana, Ooms Marcel: Vif proteins from diverse primate lentiviral lineages use a same binding site in APOBEC3G. Journal of Virology 87(21): 11861-71, Aug 2013.

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Last updated: 07/18/2014
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