Donald Ganem Explained

Donald "Don" Emil Ganem is an American physician, virologist, professor emeritus of microbiology and medicine, and the former Global Head of Infectious Diseases Research at Novartis Institutes for BioMedical Research.[1]

Early life and education

Born and raised in northern Massachusetts, Ganem graduated in 1968 from Phillips Academy Andover and in 1972 from Harvard College.[1] [2] After two years of medical school, he took an 18-month leave of absence to work on SV40 DNA replication with George Fareed.[3] In 1977, Ganem graduated with an M.D. from Harvard Medical School.[4] At Peter Bent Brigham Hospital (now Brigham and Women's Hospital), he was a resident and chief resident in internal medicine. At the University of California, San Francisco (UCSF), he did subspecialty training in infectious diseases, working in Harold Varmus's laboratory.

Career and research

Ganem became a faculty member at UCSF in 1982, rising eventually to the rank of Professor of Microbiology & Immunology and Medicine. In 1991, he also became an investigator of the Howard Hughes Medical Institute.[5]

At UCSF, his work initially focused on the molecular basis of hepatitis B virus (HBV) replication and assembly. This included fundamental studies on the synthesis and assembly of subviral[6] [7] [8] and viral[9] [10] particles, the mechanism of the encapsidation of viral RNA,[11] [12]  and detailed analyses of viral reverse transcription,[13] [14] including the first description of how linear viral DNA is formed,[15]  which led him to propose the now-accepted idea that linear DNA is the likely precursor to integrated viral genomes.[16] In the mid-1990s, he turned his attention to the study of the virology of Kaposi’s sarcoma (KS), the leading tumor of AIDS patients. After the landmark discovery of genomic fragments of a novel herpesvirus (KSHV) in KS tissue by Moore and Chang[17], Ganem's lab developed the first system for the growth of KSHV in cell culture.[18] Soon thereafter, the Ganem lab,[19] [20] the Moore and Chang lab,[21] and many subsequent groups independently published strong epidemiologic evidence that KSHV was indeed linked to the development of KS tumors. His later work on KSHV focused on identifying and characterizing the genes expressed in latent and reactivated infections,[22] [23] including those involved in gene regulation,[24] [25] [26] signal transduction,[27] [28] and immune evasion.[29] [30] [31] His studies of viral microRNAs also led his team to discover microRNAs in another family of viruses, the polyomaviruses.[32] Finally, Ganem was also part of a UCSF team (led by Dr. Joseph DeRisi) that developed a highly parallel viral screening system using DNA microarrays (and later, metagenomic DNA sequencing) to identify known and novel viral pathogens in animal and human tissue samples.[33] [34] [35]

In 2011, Ganem left UCSF to become the Global Head of Infectious Diseases Research at Novartis, where he led teams developing novel antivirals for respiratory viruses, HBV, herpesviruses, and polyomaviruses, as well as new antibiotics for multi-resistant gram-negative bacteria. Ganem left Novartis in 2018. In 2020, with Kelly Wong, Ph.D., he co-founded Via Nova Therapeutics, a biotech firm focused on antiviral drug development. He retired from active research in 2024.

Awards and honors

References

  1. Web site: Tracking a pandemic: A conversation with virologist Don Ganem, MD '68, Expert insights into COVID-19. Savard, Rita. March 26, 2020. Andover Magazine Online.
  2. Web site: Don Ganem. iBiology (ibiology.org).
  3. Neill . Ushma S. . 2014-02-03 . A conversation with Don Ganem . Journal of Clinical Investigation . en . 124 . 2 . 464–465 . 10.1172/JCI73101 . 0021-9738 . 3904632 . 24487639.
  4. Web site: Don Ganem . Member Directory, National Academy of Sciences (nasonline.org).
  5. Web site: Don Ganem, MD, Investigator / 1991–2010. Howard Hughes Medical Institute. (with links to articles on PubMed)
  6. Eble . B. E. . Lingappa . V. R. . Ganem . D. . 1986 . Hepatitis B surface antigen: an unusual secreted protein initially synthesized as a transmembrane polypeptide . Molecular and Cellular Biology . 6 . 5 . 1454–1463 . 10.1128/mcb.6.5.1454-1463.1986 . 0270-7306 . 367670 . 3023891.
  7. Eble . B. E. . MacRae . D. R. . Lingappa . V. R. . Ganem . D. . 1987 . Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen . Molecular and Cellular Biology . 7 . 10 . 3591–3601 . 10.1128/mcb.7.10.3591-3601.1987 . 0270-7306 . 368013 . 3683395.
  8. Simon . K. . Lingappa . V. R. . Ganem . D. . 1988 . Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor . The Journal of Cell Biology . 107 . 6 Pt 1 . 2163–2168 . 10.1083/jcb.107.6.2163 . 0021-9525 . 2115684 . 3198683.
  9. Ostapchuk . P. . Hearing . P. . Ganem . D. . 1994 . A dramatic shift in the transmembrane topology of a viral envelope glycoprotein accompanies hepatitis B viral morphogenesis . The EMBO Journal . 13 . 5 . 1048–1057 . 10.1002/j.1460-2075.1994.tb06353.x . 0261-4189 . 394912 . 8131739.
  10. Bruss . V. . Ganem . D. . 1991 . The role of envelope proteins in hepatitis B virus assembly . Proceedings of the National Academy of Sciences of the United States of America . 88 . 3 . 1059–1063 . 10.1073/pnas.88.3.1059 . free . 0027-8424 . 50954 . 1992457.
  11. Hirsch . R. C. . Loeb . D. D. . Pollack . J. R. . Ganem . D. . 1991 . cis-acting sequences required for encapsidation of duck hepatitis B virus pregenomic RNA . Journal of Virology . 65 . 6 . 3309–3316 . 10.1128/JVI.65.6.3309-3316.1991 . 0022-538X . 240989 . 2033673.
  12. Hirsch . R. C. . Lavine . J. E. . Chang . L. J. . Varmus . H. E. . Ganem . D. . 1990 . Polymerase gene products of hepatitis B viruses are required for genomic RNA packaging as wel as for reverse transcription . Nature . 344 . 6266 . 552–555 . 10.1038/344552a0 . 0028-0836 . 1690862.
  13. Tavis . J. E. . Perri . S. . Ganem . D. . 1994 . Hepadnavirus reverse transcription initiates within the stem-loop of the RNA packaging signal and employs a novel strand transfer . Journal of Virology . 68 . 6 . 3536–3543 . 10.1128/JVI.68.6.3536-3543.1994 . 0022-538X . 236857 . 8189492.
  14. Loeb . D. D. . Hirsch . R. C. . Ganem . D. . 1991 . Sequence-independent RNA cleavages generate the primers for plus strand DNA synthesis in hepatitis B viruses: implications for other reverse transcribing elements . The EMBO Journal . 10 . 11 . 3533–3540 . 10.1002/j.1460-2075.1991.tb04917.x . 0261-4189 . 453082 . 1915307.
  15. Staprans . S. . Loeb . D. D. . Ganem . D. . 1991 . Mutations affecting hepadnavirus plus-strand DNA synthesis dissociate primer cleavage from translocation and reveal the origin of linear viral DNA . Journal of Virology . 65 . 3 . 1255–1262 . 10.1128/JVI.65.3.1255-1262.1991 . 0022-538X . 239899 . 1704925.
  16. Yang . W. . Summers . J. . 1999 . Integration of hepadnavirus DNA in infected liver: evidence for a linear precursor . Journal of Virology . 73 . 12 . 9710–9717 . 10.1128/JVI.73.12.9710-9717.1999 . 0022-538X . 113017 . 10559280.
  17. Chang . Y. . Cesarman . E. . Pessin . M. S. . Lee . F. . Culpepper . J. . Knowles . D. M. . Moore . P. S. . 1994 . Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma . Science (New York, N.Y.) . 266 . 5192 . 1865–1869 . 10.1126/science.7997879 . 0036-8075 . 7997879. 1994Sci...266.1865C .
  18. Renne . R. . Zhong . W. . Herndier . B. . McGrath . M. . Abbey . N. . Kedes . D. . Ganem . D. . 1996 . Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture . Nature Medicine . 2 . 3 . 342–346 . 10.1038/nm0396-342 . 1078-8956 . 8612236.
  19. Kedes . D. H. . Operskalski . E. . Busch . M. . Kohn . R. . Flood . J. . Ganem . D. . 1996 . The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission . Nature Medicine . 2 . 8 . 918–924 . 10.1038/nm0896-918 . 1078-8956 . 8705863.
  20. Martin . J. N. . Ganem . D. E. . Osmond . D. H. . Page-Shafer . K. A. . Macrae . D. . Kedes . D. H. . 1998 . Sexual transmission and the natural history of human herpesvirus 8 infection . The New England Journal of Medicine . 338 . 14 . 948–954 . 10.1056/NEJM199804023381403 . 0028-4793 . 9521982.
  21. Gao . S. J. . Kingsley . L. . Li . M. . Zheng . W. . Parravicini . C. . Ziegler . J. . Newton . R. . Rinaldo . C. R. . Saah . A. . Phair . J. . Detels . R. . Chang . Y. . Moore . P. S. . 1996 . KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma . Nature Medicine . 2 . 8 . 925–928 . 10.1038/nm0896-925 . 1078-8956 . 8705864.
  22. Zhong . W. . Wang . H. . Herndier . B. . Ganem . D. . 1996 . Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma . Proceedings of the National Academy of Sciences of the United States of America . 93 . 13 . 6641–6646 . 10.1073/pnas.93.13.6641 . free . 0027-8424 . 39079 . 8692871.
  23. Dittmer . D. . Lagunoff . M. . Renne . R. . Staskus . K. . Haase . A. . Ganem . D. . 1998 . A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus . Journal of Virology . 72 . 10 . 8309–8315 . 10.1128/JVI.72.10.8309-8315.1998 . 0022-538X . 110196 . 9733875.
  24. Lukac . D. M. . Renne . R. . Kirshner . J. R. . Ganem . D. . 1998 . Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein . Virology . 252 . 2 . 304–312 . 10.1006/viro.1998.9486 . 0042-6822 . 9878608.
  25. Kirshner . J. R. . Lukac . D. M. . Chang . J. . Ganem . D. . 2000 . Kaposi's sarcoma-associated herpesvirus open reading frame 57 encodes a posttranscriptional regulator with multiple distinct activities . Journal of Virology . 74 . 8 . 3586–3597 . 10.1128/jvi.74.8.3586-3597.2000 . 0022-538X . 111868 . 10729134.
  26. Liang . Y. . Chang . J. . Lynch . S. J. . Lukac . D. M. . Ganem . D. . 2002 . The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway . Genes & Development . 16 . 15 . 1977–1989 . 10.1101/gad.996502 . 0890-9369 . 186409 . 12154127.
  27. Lagunoff . M. . Majeti . R. . Weiss . A. . Ganem . D. . 1999 . Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus . Proceedings of the National Academy of Sciences of the United States of America . 96 . 10 . 5704–5709 . 10.1073/pnas.96.10.5704 . free . 0027-8424 . 21924 . 10318948.
  28. Grossmann . C. . Podgrabinska . S. . Skobe . M. . Ganem . D. . 2006 . Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype . Journal of Virology . 80 . 14 . 7179–7185 . 10.1128/JVI.01603-05 . 0022-538X . 1489050 . 16809323.
  29. Coscoy . L. . Ganem . D. . 2000 . Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis . Proceedings of the National Academy of Sciences of the United States of America . 97 . 14 . 8051–8056 . 10.1073/pnas.140129797 . free . 0027-8424 . 16668 . 10859362.
  30. Coscoy . L. . Ganem . D. . 2001 . A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation . The Journal of Clinical Investigation . 107 . 12 . 1599–1606 . 10.1172/JCI12432 . 0021-9738 . 200195 . 11413168.
  31. Madrid . A. S. . Ganem . D. . 2012 . Kaposi's sarcoma-associated herpesvirus ORF54/dUTPase downregulates a ligand for the NK activating receptor NKp44 . Journal of Virology . 86 . 16 . 8693–8704 . 10.1128/JVI.00252-12 . 1098-5514 . 3421743 . 22674989.
  32. Sullivan . C. S. . Grundhoff . A. T. . Tevethia . S. . Pipas . J. M. . Ganem . D. . 2005 . SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells . Nature . 435 . 7042 . 682–686 . 10.1038/nature03576 . 1476-4687 . 15931223.
  33. Wang . D. . Coscoy . L. . Zylberberg . M. . Avila . P. C. . Boushey . H. A. . Ganem . D. . DeRisi . J. L. . 2002 . Microarray-based detection and genotyping of viral pathogens . Proceedings of the National Academy of Sciences of the United States of America . en . 99 . 24 . 15687–15692 . 10.1073/pnas.242579699 . free . 137777 . 12429852.
  34. Kistler . A. L. . Gancz . A. . Clubb . S. . Skewes-Cox . P. . Fischer . K. . Sorber . K. . Chiu . C. Y. . Lublin . A. . Mechani . S. . Farnoushi . Y. . Greninger . A. . Wen . C. C. . Karlene . S. B. . Ganem . D. . DeRisi . J. L. . 2008 . Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: identification of a candidate etiologic agent . Virology Journal . 5 . 1 . 88 . 10.1186/1743-422X-5-88 . free . 1743-422X . 2546392 . 18671869.
  35. Chandriani . S. . Skewes-Cox . P. . Zhong . W. . Ganem . D. E. . Divers . T. J. . Van Blaricum . A. J. . Tennant . B. C. . Kistler . A. L. . 2013 . Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis . Proceedings of the National Academy of Sciences of the United States of America . 110 . 15 . E1407–1415 . 10.1073/pnas.1219217110 . free . 1091-6490 . 3625295 . 23509292.
  36. Web site: Donald Emil Ganem. American Academy of Arts & Sciences (amacad.org). 18 October 2023 .
  37. Web site: Past Presidents. American Society for Virology (asv.org).

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