Beatrice H. Hahn

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. (Medicine)
University of Munich, Munich, Germany, 1981.
Intern (Medicine)
University of Munich, 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:

Research Assistant Professors:
Fred Bibollet-Ruche, Ph.D.

Senior Research Investigators:
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:
Fang-Hua Lee

Students:
Hannah Barbian
Shilpa S. Iyer
(8/10) B.S., Fergusson College, M.S. University of Pune, Pune, India. Fitness costs associated with HIV-1 immune escape
Elizabeth Loy
Edward Kreider

Technicians:
Andrew G. Smith (07/11)
Timothy Decker (10/12)
Catharine Bahari (09/14)

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
Nicholas F. Parrish, M.D., Ph.D.
Surgery Resident, Vanderbilt University
Sesh Sundararaman, Ph.D. MSTP Student, University of Pennsylvania Perelman School of Medicine

Selected Publications

Lopker Michael J, Del Prete Gregory Q, Estes Jacob D, Li Hui, Reid Carolyn, Newman Laura, Lipkey Leslie, Camus Celine, Easlick Juliet L, Wang Shuyi, Decker Julie M, Bar Katharine J, Learn Gerald, Pal Ranajit, Weiss Deborah E, Hahn Beatrice H, Lifson Jeffrey D, Shaw George M, Keele Brandon F: Derivation and characterization of pathogenic transmitted/founder molecular clones from SIVsmE660 and SIVmac251 following mucosal infection. Journal of virology Jul 2016.

Loy Dorothy E, Liu Weimin, Li Yingying, Learn Gerald H, Plenderleith Lindsey J, Sundararaman Sesh A, Sharp Paul M, Hahn Beatrice H: Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. International journal for parasitology Jul 2016.

Scheid Johannes F, Horwitz Joshua A, Bar-On Yotam, Kreider Edward F, Lu Ching-Lan, Lorenzi Julio C C, Feldmann Anna, Braunschweig Malte, Nogueira Lilian, Oliveira Thiago, Shimeliovich Irina, Patel Roshni, Burke Leah, Cohen Yehuda Z, Hadrigan Sonya, Settler Allison, Witmer-Pack Maggi, West Anthony P, Juelg Boris, Keler Tibor, Hawthorne Thomas, Zingman Barry, Gulick Roy M, Pfeifer Nico, Learn Gerald H, Seaman Michael S, Bjorkman Pamela J, Klein Florian, Schlesinger Sarah J, Walker Bruce D, Hahn Beatrice H, Nussenzweig Michel C, Caskey Marina: HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature Jun 2016.

Li Hui, Wang Shuyi, Kong Rui, Ding Wenge, Lee Fang-Hua, Parker Zahra, Kim Eunlim, Learn Gerald H, Hahn Paul, Policicchio Ben, Brocca-Cofano Egidio, Deleage Claire, Hao Xingpei, Chuang Gwo-Yu, Gorman Jason, Gardner Matthew, Lewis Mark G, Hatziioannou Theodora, Santra Sampa, Apetrei Cristian, Pandrea Ivona, Alam S Munir, Liao Hua-Xin, Shen Xiaoying, Tomaras Georgia D, Farzan Michael, Chertova Elena, Keele Brandon F, Estes Jacob D, Lifson Jeffrey D, Doms Robert W, Montefiori David C, Haynes Barton F, Sodroski Joseph G, Kwong Peter D, Hahn Beatrice H, Shaw George M: Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proceedings of the National Academy of Sciences of the United States of America 113(24): E3413-22, Jun 2016.

Terio Karen A, Lonsdorf Elizabeth V, Kinsel Michael J, Raphael Jane, Lipende Iddi, Collins Anthony, Li Yingying, Hahn Beatrice H, Travis Dominic A, Gillespie Thomas R: Oesophagostomiasis in non-human primates of Gombe National Park, Tanzania. American journal of primatology Jun 2016.

Schoofs Till, Klein Florian, Braunschweig Malte, Kreider Edward F, Feldmann Anna, Nogueira Lilian, Oliveira Thiago, Lorenzi Julio C C, Parrish Erica H, Learn Gerald H, West Anthony P, Bjorkman Pamela J, Schlesinger Sarah J, Seaman Michael S, Czartoski Julie, McElrath M Juliana, Pfeifer Nico, Hahn Beatrice H, Caskey Marina, Nussenzweig Michel C: HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science (New York, N.Y.) 352(6288): 997-1001, May 2016.

Apps Richard, Del Prete Gregory Q, Chatterjee Pramita, Lara Abigail, Brumme Zabrina L, Brockman Mark A, Neil Stuart, Pickering Suzanne, Schneider Douglas K, Piechocka-Trocha Alicja, Walker Bruce D, Thomas Rasmi, Shaw George M, Hahn Beatrice H, Keele Brandon F, Lifson Jeffrey D, Carrington Mary: HIV-1 Vpu Mediates HLA-C Downregulation. Cell host & microbe 19(5): 686-95, May 2016.

Bonsignori Mattia, Zhou Tongqing, Sheng Zizhang, Chen Lei, Gao Feng, Joyce M Gordon, Ozorowski Gabriel, Chuang Gwo-Yu, Schramm Chaim A, Wiehe Kevin, Alam S Munir, Bradley Todd, Gladden Morgan A, Hwang Kwan-Ki, Iyengar Sheelah, Kumar Amit, Lu Xiaozhi, Luo Kan, Mangiapani Michael C, Parks Robert J, Song Hongshuo, Acharya Priyamvada, Bailer Robert T, Cao Allen, Druz Aliaksandr, Georgiev Ivelin S, Kwon Young D, Louder Mark K, Zhang Baoshan, Zheng Anqi, Hill Brenna J, Kong Rui, Soto Cinque, Mullikin James C, Douek Daniel C, Montefiori David C, Moody Michael A, Shaw George M, Hahn Beatrice H, Kelsoe Garnett, Hraber Peter T, Korber Bette T, Boyd Scott D, Fire Andrew Z, Kepler Thomas B, Shapiro Lawrence, Ward Andrew B, Mascola John R, Liao Hua-Xin, Kwong Peter D, Haynes Barton F: Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell 165(2): 449-63, Mar 2016.

Haynes Barton F, Shaw George M, Korber Bette, Kelsoe Garnett, Sodroski Joseph, Hahn Beatrice H, Borrow Persephone, McMichael Andrew J: HIV-Host Interactions: Implications for Vaccine Design. Cell host & microbe 19(3): 292-303, Feb 2016.

Menger David J, Omusula Philemon, Wouters Karlijn, Oketch Charles, Carreira Ana S, Durka Maxime, Derycke Jean-Luc, Loy Dorothy E, Hahn Beatrice H, Mukabana Wolfgang R, Mweresa Collins K, van Loon Joop J A, Takken Willem, Hiscox Alexandra: Eave Screening and Push-Pull Tactics to Reduce House Entry by Vectors of Malaria. The American journal of tropical medicine and hygiene 94(4): 868-78, Feb 2016.

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Last updated: 04/19/2016
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