Beatrice H. Hahn, M.D.

faculty photo
Professor of Medicine
Department: Medicine
Graduate Group Affiliations

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
Education:
M.D.
University of Munich, Medical School, Munich, Germany, 1981.
Doctorate (Medicine)
University of Munich, Medical School, Munich, Germany, 1982.
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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

Richard Jonathan, Veillette Maxime, Brassard Nathalie, Iyer Shilpa S, Roger Michel, Martin Loïc, Pazgier Marzena, Schön Arne, Freire Ernesto, Routy Jean-Pierre, Smith Amos B, Park Jongwoo, Jones David M, Courter Joel R, Melillo Bruno N, Kaufmann Daniel E, Hahn Beatrice H, Permar Sallie R, Haynes Barton F, Madani Navid, Sodroski Joseph G, Finzi Andrés: CD4 mimetics sensitize HIV-1-infected cells to ADCC. Proceedings of the National Academy of Sciences of the United States of America May 2015.

D'arc Mirela, Ayouba Ahidjo, Esteban Amandine, Learn Gerald H, Boué Vanina, Liegeois Florian, Etienne Lucie, Tagg Nikki, Leendertz Fabian H, Boesch Christophe, Madinda Nadège F, Robbins Martha M, Gray Maryke, Cournil Amandine, Ooms Marcel, Letko Michael, Simon Viviana A, Sharp Paul M, Hahn Beatrice H, Delaporte Eric, Mpoudi Ngole Eitel, Peeters Martine: Origin of the HIV-1 group O epidemic in western lowland gorillas. Proceedings of the National Academy of Sciences of the United States of America 112(11): E1343-52, Mar 2015.

Gardner Matthew R, Kattenhorn Lisa M, Kondur Hema R, von Schaewen Markus, Dorfman Tatyana, Chiang Jessica J, Haworth Kevin G, Decker Julie M, Alpert Michael D, Bailey Charles C, Neale Ernest S, Fellinger Christoph H, Joshi Vinita R, Fuchs Sebastian P, Martinez-Navio Jose M, Quinlan Brian D, Yao Annie Y, Mouquet Hugo, Gorman Jason, Zhang Baoshan, Poignard Pascal, Nussenzweig Michel C, Burton Dennis R, Kwong Peter D, Piatak Michael, Lifson Jeffrey D, Gao Guangping, Desrosiers Ronald C, Evans David T, Hahn Beatrice H, Ploss Alexander, Cannon Paula M, Seaman Michael S, Farzan Michael: AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519(7541): 87-91, Mar 2015.

Sauter Daniel, Hotter Dominik, Van Driessche Benoît, Stürzel Christina M, Kluge Silvia F, Wildum Steffen, Yu Hangxing, Baumann Bernd, Wirth Thomas, Plantier Jean-Christophe, Leoz Marie, Hahn Beatrice H, Van Lint Carine, Kirchhoff Frank: Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins. Cell Reports 10(4): 586-99, Feb 2015.

Moeller Andrew H, Peeters Martine, Ayouba Ahidjo, Ngole Eitel Mpoudi, Esteban Amadine, Hahn Beatrice H, Ochman Howard: Stability of the gorilla microbiome despite simian immunodeficiency virus infection. Molecular Ecology 24(3): 690-7, Feb 2015.

Asmal Mohammed, Luedemann Corinne, Lavine Christy L, Mach Linh V, Balachandran Harikrishnan, Brinkley Christie, Denny Thomas N, Lewis Mark G, Anderson Hanne, Pal Ranajit, Sok Devin, Le Khoa, Pauthner Matthias, Hahn Beatrice H, Shaw George M, Seaman Michael S, Letvin Norman L, Burton Dennis R, Sodroski Joseph G, Haynes Barton F, Santra Sampa: Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes. Virology 475: 37-45, Jan 2015.

Yue Ling, Pfafferott Katja J, Baalwa Joshua, Conrod Karen, Dong Catherine C, Chui Cecilia, Rong Rong, Claiborne Daniel T, Prince Jessica L, Tang Jianming, Ribeiro Ruy M, Cormier Emmanuel, Hahn Beatrice H, Perelson Alan S, Shaw George M, Karita Etienne, Gilmour Jill, Goepfert Paul, Derdeyn Cynthia A, Allen Susan A, Borrow Persephone, Hunter Eric: Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. PLoS Pathogens 11(1): e1004565, Jan 2015.

Cohn Lillian B, Silva Israel T, Oliveira Thiago Y, Rosales Rafael A, Parrish Erica H, Learn Gerald H, Hahn Beatrice H, Czartoski Julie L, McElrath M Juliana, Lehmann Clara, Klein Florian, Caskey Marina, Walker Bruce D, Siliciano Janet D, Siliciano Robert F, Jankovic Mila, Nussenzweig Michel C: HIV-1 integration landscape during latent and active infection. Cell 160(3): 420-32, Jan 2015.

Barbian Hannah J, Decker Julie M, Bibollet-Ruche Frederic, Galimidi Rachel P, West Anthony P, Learn Gerald H, Parrish Nicholas F, Iyer Shilpa S, Li Yingying, Pace Craig S, Song Ruijiang, Huang Yaoxing, Denny Thomas N, Mouquet Hugo, Martin Loic, Acharya Priyamvada, Zhang Baoshan, Kwong Peter D, Mascola John R, Verrips C Theo, Strokappe Nika M, Rutten Lucy, McCoy Laura E, Weiss Robin A, Brown Corrine S, Jackson Raven, Silvestri Guido, Connors Mark, Burton Dennis R, Shaw George M, Nussenzweig Michel C, Bjorkman Pamela J, Ho David D, Farzan Michael, Hahn Beatrice H: Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. mBio 6(2), 2015.

Busula Annette O, Takken Willem, Loy Dorothy E, Hahn Beatrice H, Mukabana Wolfgang R, Verhulst Niels O: Mosquito host preferences affect their response to synthetic and natural odour blends. Malaria Journal 14(1): 133, 2015.

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Last updated: 05/27/2015
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