Donald Ganem

{{short description|American physician and virologist}} '''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.<ref name=Savard>{{cite web|title=Tracking a pandemic: A conversation with virologist Don Ganem, MD '68, Expert insights into COVID-19|author=Savard, Rita|date=March 26, 2020|website=Andover Magazine Online|url=https://www.andover.edu/news/2020/tracking-a-pandemic}}</ref>

==Early life and education== Born and raised in northern Massachusetts, Ganem graduated in 1968 from Phillips Academy Andover and in 1972 from Harvard College.<ref name=Savard/><ref name=iBiology>{{cite web|title=Don Ganem|website=iBiology (ibiology.org)|url=https://www.ibiology.org/speakers/don-ganem/}}</ref> After two years of medical school, he took an 18-month leave of absence to work on SV40 DNA replication with George Fareed.<ref name=":0">{{Cite journal |last=Neill |first=Ushma S. |date=2014-02-03 |title=A conversation with Don Ganem |journal=Journal of Clinical Investigation |language=en |volume=124 |issue=2 |pages=464–465 |doi=10.1172/JCI73101 |issn=0021-9738 |pmc=3904632 |pmid=24487639}}</ref> In 1977, Ganem graduated with an M.D. from Harvard Medical School.<ref name="healthgrades">{{cite web |title=Don Ganem |url=https://www.nasonline.org/directory-entry/don-ganem-0humwb/ |website=Member Directory, National Academy of Sciences (nasonline.org)}}</ref> 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.<ref name=":0" />

==Career and research== Ganem became a faculty member at UCSF in 1982,<ref name="iBiology" /> rising eventually to the rank of Professor of Microbiology & Immunology and Medicine.<ref name=":1" /> In 1991, he also became an investigator of the Howard Hughes Medical Institute.<ref name=":1">{{cite web|title=Don Ganem, MD, Investigator / 1991–2010|website=Howard Hughes Medical Institute|url=https://www.hhmi.org/scientists/don-ganem}} (with links to articles on PubMed)</ref>

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<ref>{{Cite journal |last1=Eble |first1=B. E. |last2=Lingappa |first2=V. R. |last3=Ganem |first3=D. |date=1986 |title=Hepatitis B surface antigen: an unusual secreted protein initially synthesized as a transmembrane polypeptide |journal=Molecular and Cellular Biology |volume=6 |issue=5 |pages=1454–1463 |doi=10.1128/mcb.6.5.1454-1463.1986 |issn=0270-7306 |pmc=367670 |pmid=3023891}}</ref><ref>{{Cite journal |last1=Eble |first1=B. E. |last2=MacRae |first2=D. R. |last3=Lingappa |first3=V. R. |last4=Ganem |first4=D. |date=1987 |title=Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen |journal=Molecular and Cellular Biology |volume=7 |issue=10 |pages=3591–3601 |doi=10.1128/mcb.7.10.3591-3601.1987 |issn=0270-7306 |pmc=368013 |pmid=3683395}}</ref><ref>{{Cite journal |last1=Simon |first1=K. |last2=Lingappa |first2=V. R. |last3=Ganem |first3=D. |date=1988 |title=Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor |journal=The Journal of Cell Biology |volume=107 |issue=6 Pt 1 |pages=2163–2168 |doi=10.1083/jcb.107.6.2163 |issn=0021-9525 |pmc=2115684 |pmid=3198683}}</ref> and viral<ref>{{Cite journal |last1=Ostapchuk |first1=P. |last2=Hearing |first2=P. |last3=Ganem |first3=D. |date=1994 |title=A dramatic shift in the transmembrane topology of a viral envelope glycoprotein accompanies hepatitis B viral morphogenesis |journal=The EMBO Journal |volume=13 |issue=5 |pages=1048–1057 |doi=10.1002/j.1460-2075.1994.tb06353.x |issn=0261-4189 |pmc=394912 |pmid=8131739}}</ref><ref>{{Cite journal |last1=Bruss |first1=V. |last2=Ganem |first2=D. |date=1991 |title=The role of envelope proteins in hepatitis B virus assembly |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=88 |issue=3 |pages=1059–1063 |doi=10.1073/pnas.88.3.1059 |doi-access=free |issn=0027-8424 |pmc=50954 |pmid=1992457}}</ref> particles, the mechanism of the encapsidation of viral RNA,<ref>{{Cite journal |last1=Hirsch |first1=R. C. |last2=Loeb |first2=D. D. |last3=Pollack |first3=J. R. |last4=Ganem |first4=D. |date=1991 |title=cis-acting sequences required for encapsidation of duck hepatitis B virus pregenomic RNA |journal=Journal of Virology |volume=65 |issue=6 |pages=3309–3316 |doi=10.1128/JVI.65.6.3309-3316.1991 |issn=0022-538X |pmc=240989 |pmid=2033673}}</ref><ref>{{Cite journal |last1=Hirsch |first1=R. C. |last2=Lavine |first2=J. E. |last3=Chang |first3=L. J. |last4=Varmus |first4=H. E. |last5=Ganem |first5=D. |date=1990 |title=Polymerase gene products of hepatitis B viruses are required for genomic RNA packaging as wel as for reverse transcription |journal=Nature |volume=344 |issue=6266 |pages=552–555 |doi=10.1038/344552a0 |issn=0028-0836 |pmid=1690862}}</ref> and detailed analyses of viral reverse transcription,<ref>{{Cite journal |last1=Tavis |first1=J. E. |last2=Perri |first2=S. |last3=Ganem |first3=D. |date=1994 |title=Hepadnavirus reverse transcription initiates within the stem-loop of the RNA packaging signal and employs a novel strand transfer |journal=Journal of Virology |volume=68 |issue=6 |pages=3536–3543 |doi=10.1128/JVI.68.6.3536-3543.1994 |issn=0022-538X |pmc=236857 |pmid=8189492}}</ref><ref>{{Cite journal |last1=Loeb |first1=D. D. |last2=Hirsch |first2=R. C. |last3=Ganem |first3=D. |date=1991 |title=Sequence-independent RNA cleavages generate the primers for plus strand DNA synthesis in hepatitis B viruses: implications for other reverse transcribing elements |journal=The EMBO Journal |volume=10 |issue=11 |pages=3533–3540 |doi=10.1002/j.1460-2075.1991.tb04917.x |issn=0261-4189 |pmc=453082 |pmid=1915307}}</ref> including the first description of how linear viral DNA is formed,<ref>{{Cite journal |last1=Staprans |first1=S. |last2=Loeb |first2=D. D. |last3=Ganem |first3=D. |date=1991 |title=Mutations affecting hepadnavirus plus-strand DNA synthesis dissociate primer cleavage from translocation and reveal the origin of linear viral DNA |journal=Journal of Virology |volume=65 |issue=3 |pages=1255–1262 |doi=10.1128/JVI.65.3.1255-1262.1991 |issn=0022-538X |pmc=239899 |pmid=1704925}}</ref> which led him to propose the now-accepted idea that linear DNA is the likely precursor to integrated viral genomes.<ref>{{Cite journal |last1=Yang |first1=W. |last2=Summers |first2=J. |date=1999 |title=Integration of hepadnavirus DNA in infected liver: evidence for a linear precursor |journal=Journal of Virology |volume=73 |issue=12 |pages=9710–9717 |doi=10.1128/JVI.73.12.9710-9717.1999 |issn=0022-538X |pmc=113017 |pmid=10559280}}</ref> 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,<ref>{{Cite journal |last1=Chang |first1=Y. |last2=Cesarman |first2=E. |last3=Pessin |first3=M. S. |last4=Lee |first4=F. |last5=Culpepper |first5=J. |last6=Knowles |first6=D. M. |last7=Moore |first7=P. S. |date=1994 |title=Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma |journal=Science |volume=266 |issue=5192 |pages=1865–1869 |doi=10.1126/science.7997879 |issn=0036-8075 |pmid=7997879|bibcode=1994Sci...266.1865C }}</ref> Ganem's lab developed the first system for the growth of KSHV in cell culture.<ref>{{Cite journal |last1=Renne |first1=R. |last2=Zhong |first2=W. |last3=Herndier |first3=B. |last4=McGrath |first4=M. |last5=Abbey |first5=N. |last6=Kedes |first6=D. |last7=Ganem |first7=D. |date=1996 |title=Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture |journal=Nature Medicine |volume=2 |issue=3 |pages=342–346 |doi=10.1038/nm0396-342 |issn=1078-8956 |pmid=8612236}}</ref> Soon thereafter, the Ganem lab,<ref>{{Cite journal |last1=Kedes |first1=D. H. |last2=Operskalski |first2=E. |last3=Busch |first3=M. |last4=Kohn |first4=R. |last5=Flood |first5=J. |last6=Ganem |first6=D. |date=1996 |title=The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission |journal=Nature Medicine |volume=2 |issue=8 |pages=918–924 |doi=10.1038/nm0896-918 |issn=1078-8956 |pmid=8705863}}</ref><ref>{{Cite journal |last1=Martin |first1=J. N. |last2=Ganem |first2=D. E. |last3=Osmond |first3=D. H. |last4=Page-Shafer |first4=K. A. |last5=Macrae |first5=D. |last6=Kedes |first6=D. H. |date=1998 |title=Sexual transmission and the natural history of human herpesvirus 8 infection |journal=The New England Journal of Medicine |volume=338 |issue=14 |pages=948–954 |doi=10.1056/NEJM199804023381403 |issn=0028-4793 |pmid=9521982}}</ref> the Moore and Chang lab,<ref>{{Cite journal |last1=Gao |first1=S. J. |last2=Kingsley |first2=L. |last3=Li |first3=M. |last4=Zheng |first4=W. |last5=Parravicini |first5=C. |last6=Ziegler |first6=J. |last7=Newton |first7=R. |last8=Rinaldo |first8=C. R. |last9=Saah |first9=A. |last10=Phair |first10=J. |last11=Detels |first11=R. |last12=Chang |first12=Y. |last13=Moore |first13=P. S. |date=1996 |title=KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma |journal=Nature Medicine |volume=2 |issue=8 |pages=925–928 |doi=10.1038/nm0896-925 |issn=1078-8956 |pmid=8705864}}</ref> 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,<ref>{{Cite journal |last1=Zhong |first1=W. |last2=Wang |first2=H. |last3=Herndier |first3=B. |last4=Ganem |first4=D. |date=1996 |title=Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=93 |issue=13 |pages=6641–6646 |doi=10.1073/pnas.93.13.6641 |doi-access=free |issn=0027-8424 |pmc=39079 |pmid=8692871}}</ref><ref>{{Cite journal |last1=Dittmer |first1=D. |last2=Lagunoff |first2=M. |last3=Renne |first3=R. |last4=Staskus |first4=K. |last5=Haase |first5=A. |last6=Ganem |first6=D. |date=1998 |title=A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus |journal=Journal of Virology |volume=72 |issue=10 |pages=8309–8315 |doi=10.1128/JVI.72.10.8309-8315.1998 |issn=0022-538X |pmc=110196 |pmid=9733875}}</ref> including those involved in gene regulation,<ref>{{Cite journal |last1=Lukac |first1=D. M. |last2=Renne |first2=R. |last3=Kirshner |first3=J. R. |last4=Ganem |first4=D. |date=1998 |title=Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein |journal=Virology |volume=252 |issue=2 |pages=304–312 |doi=10.1006/viro.1998.9486 |issn=0042-6822 |pmid=9878608}}</ref><ref>{{Cite journal |last1=Kirshner |first1=J. R. |last2=Lukac |first2=D. M. |last3=Chang |first3=J. |last4=Ganem |first4=D. |date=2000 |title=Kaposi's sarcoma-associated herpesvirus open reading frame 57 encodes a posttranscriptional regulator with multiple distinct activities |journal=Journal of Virology |volume=74 |issue=8 |pages=3586–3597 |doi=10.1128/jvi.74.8.3586-3597.2000 |issn=0022-538X |pmc=111868 |pmid=10729134}}</ref><ref>{{Cite journal |last1=Liang |first1=Y. |last2=Chang |first2=J. |last3=Lynch |first3=S. J. |last4=Lukac |first4=D. M. |last5=Ganem |first5=D. |date=2002 |title=The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway |journal=Genes & Development |volume=16 |issue=15 |pages=1977–1989 |doi=10.1101/gad.996502 |issn=0890-9369 |pmc=186409 |pmid=12154127}}</ref> signal transduction,<ref>{{Cite journal |last1=Lagunoff |first1=M. |last2=Majeti |first2=R. |last3=Weiss |first3=A. |last4=Ganem |first4=D. |date=1999 |title=Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=96 |issue=10 |pages=5704–5709 |doi=10.1073/pnas.96.10.5704 |doi-access=free |issn=0027-8424 |pmc=21924 |pmid=10318948}}</ref><ref>{{Cite journal |last1=Grossmann |first1=C. |last2=Podgrabinska |first2=S. |last3=Skobe |first3=M. |last4=Ganem |first4=D. |date=2006 |title=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=Journal of Virology |volume=80 |issue=14 |pages=7179–7185 |doi=10.1128/JVI.01603-05 |issn=0022-538X |pmc=1489050 |pmid=16809323}}</ref> and immune evasion.<ref>{{Cite journal |last1=Coscoy |first1=L. |last2=Ganem |first2=D. |date=2000 |title=Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=97 |issue=14 |pages=8051–8056 |doi=10.1073/pnas.140129797 |doi-access=free |issn=0027-8424 |pmc=16668 |pmid=10859362}}</ref><ref>{{Cite journal |last1=Coscoy |first1=L. |last2=Ganem |first2=D. |date=2001 |title=A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation |journal=The Journal of Clinical Investigation |volume=107 |issue=12 |pages=1599–1606 |doi=10.1172/JCI12432 |issn=0021-9738 |pmc=200195 |pmid=11413168}}</ref><ref>{{Cite journal |last1=Madrid |first1=A. S. |last2=Ganem |first2=D. |date=2012 |title=Kaposi's sarcoma-associated herpesvirus ORF54/dUTPase downregulates a ligand for the NK activating receptor NKp44 |journal=Journal of Virology |volume=86 |issue=16 |pages=8693–8704 |doi=10.1128/JVI.00252-12 |issn=1098-5514 |pmc=3421743 |pmid=22674989}}</ref> His studies of viral microRNAs also led his team to discover microRNAs in another family of viruses, the polyomaviruses.<ref>{{Cite journal |last1=Sullivan |first1=C. S. |last2=Grundhoff |first2=A. T. |last3=Tevethia |first3=S. |last4=Pipas |first4=J. M. |last5=Ganem |first5=D. |date=2005 |title=SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells |journal=Nature |volume=435 |issue=7042 |pages=682–686 |doi=10.1038/nature03576 |issn=1476-4687 |pmid=15931223}}</ref> 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.<ref>{{Cite journal |last1=Wang |first1=D. |last2=Coscoy |first2=L. |last3=Zylberberg |first3=M. |last4=Avila |first4=P. C. |last5=Boushey |first5=H. A. |last6=Ganem |first6=D. |last7=DeRisi |first7=J. L. |date=2002 |title=Microarray-based detection and genotyping of viral pathogens |journal=Proceedings of the National Academy of Sciences of the United States of America |language=en |volume=99 |issue=24 |pages=15687–15692 |doi=10.1073/pnas.242579699 |doi-access=free |pmc=137777 |pmid=12429852}}</ref><ref>{{Cite journal |last1=Kistler |first1=A. L. |last2=Gancz |first2=A. |last3=Clubb |first3=S. |last4=Skewes-Cox |first4=P. |last5=Fischer |first5=K. |last6=Sorber |first6=K. |last7=Chiu |first7=C. Y. |last8=Lublin |first8=A. |last9=Mechani |first9=S. |last10=Farnoushi |first10=Y. |last11=Greninger |first11=A. |last12=Wen |first12=C. C. |last13=Karlene |first13=S. B. |last14=Ganem |first14=D. |last15=DeRisi |first15=J. L. |date=2008 |title=Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: identification of a candidate etiologic agent |journal=Virology Journal |volume=5 |issue=1 |pages=88 |doi=10.1186/1743-422X-5-88 |doi-access=free |issn=1743-422X |pmc=2546392 |pmid=18671869}}</ref><ref>{{Cite journal |last1=Chandriani |first1=S. |last2=Skewes-Cox |first2=P. |last3=Zhong |first3=W. |last4=Ganem |first4=D. E. |last5=Divers |first5=T. J. |last6=Van Blaricum |first6=A. J. |last7=Tennant |first7=B. C. |last8=Kistler |first8=A. L. |date=2013 |title=Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=110 |issue=15 |pages=E1407–1415 |doi=10.1073/pnas.1219217110 |doi-access=free |issn=1091-6490 |pmc=3625295 |pmid=23509292}}</ref>

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== * 2003 — Elected to the Institute of Medicine<ref name="iBiology" /> (now called the National Academy of Medicine) * 2004 — Elected to the American Academy of Arts and Sciences<ref>{{cite web|title=Donald Emil Ganem|website=American Academy of Arts & Sciences (amacad.org)|date=18 October 2023 |url=https://www.amacad.org/person/donald-emil-ganem}}</ref> * 2006–2007 — President of the American Society for Virology<ref>{{cite web|title=Past Presidents|website=American Society for Virology (asv.org)|url=https://asv.org/past-presidents/}}</ref> * 2010 — Elected to the National Academy of Sciences<ref name="healthgrades" /> * 2016 — Awarded the UCSF Medal for distinguished service to the university

==References== <references/>

==External links== *{{cite web |title=Donald Ganem, MD |website=UCSF Profiles, University of California, San Francisco |url=https://profiles.ucsf.edu/donald.ganem}} (online links to many of Ganem's publications) * Don Ganem (Novartis Institutes for Biomedical Research) 4 Part Lecture, 2010, iBiology **{{cite web|title=Part 1: Kaposi's Sarcoma: The Disease|date=March 24, 2010|website=YouTube|url=https://www.youtube.com/watch?v=D7J9dm1d3dQ}} **{{cite web|title=Part 2: The Virus|date=March 24, 2010|website=YouTube|url=https://www.youtube.com/watch?v=c9shiDUISmE}} **{{cite web|title=Part 3: KSHV Latency and KS Pathogenesis|date=March 24, 2010|website=YouTube|url=https://www.youtube.com/watch?v=GC1to219D_Y}} **{{cite web|title=Part 4: Is KSHV Latency the Whole Story?|date=March 24, 2010|website=YouTube|url=https://www.youtube.com/watch?v=kBKbSiGb58E}} *{{cite web|title=JCI's Conversations with Giants in Medicine: Don Ganem|date=February 3, 2014|publisher=Journal of Clinical Investigation|website=YouTube|url=https://www.youtube.com/watch?v=aY2vtoJVBnI}} *{{cite web|title=2016 UCSF Medal Recipient: Don Ganem|date=November 10, 2016|publisher=UC San Francisco (UCSF)|website=YouTube|url=https://www.youtube.com/watch?v=KMpa9TFNB_I}}

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{{DEFAULTSORT:Ganem, Donald}} Category:American virologists Category:American immunologists Category:20th-century American medical doctors Category:21st-century American medical doctors Category:Phillips Academy alumni Category:Harvard College alumni Category:Harvard Medical School alumni Category:Members of the National Academy of Medicine Category:Members of the United States National Academy of Sciences Category:Fellows of the American Academy of Arts and Sciences Category:Howard Hughes Medical Investigators Category:UCSF School of Medicine faculty Category:Novartis people Category:American people of Lebanese descent Category:1950 births Category:Living people