• Gantt, Soren

    Titles

    Investigator, BC Children's Hospital
    Associate Professor, Division of Infectious Diseases
    Faculty of Medicine, University of British Columbia

    Degrees / Designations
    MD, PhD, MPH
    Primary Area of Research
    Healthy Starts
    Secondary Area(s) of Research
    Phone
    604-875-2151
    Fax
    Lab Phone
    Mailing Address
    Affiliate Websites
    Research Areas
    • Herpesvirus infections
    • Kaposi sarcoma
    • Epstein-Barr virus 
    • Cytomegalovirus
    • HIV
    • Cancer 
    • Antiviral 
    • Antiretroviral
    • Immune response
    Summary
    Current Projects

    Infections with human herpesviruses (HHVs), such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus (KSHV), cause an enormous amount of morbidity and mortality worldwide. Although nearly everyone becomes infected with one or more of these viruses, most have no significant illness from them. However, in young infants or people immunocompromised by HIV or having a transplant, these viruses frequently cause a range of severe infections and cancers. Vaccines or drugs to prevent these infections or their complications would have profound public health implications, but first additional research is required to better understand the underlying pathogenesis. As such, we carry out translational research studies, utilizing cohorts of children in Africa and North America as well as epidemiologic, clinical, and molecular approaches, to address fundamental questions about how to prevent and treat HHV-related diseases.

    We are particularly interested in the role of HHV infections very early in life. For example, CMV infects approximately 1% of all infants in utero, which frequently results in neurologic sequelae like deafness and mental retardation; postnatal infections, however, are normally benign. Similarly, high risk for Burkitt's lymphoma, one of the most common childhood cancers in Africa, appears to be due to EBV infection in early infancy combined with exposure to malaria. We have established a cohort of children in Uganda who were followed every week during the first year of life to study CMV and EBV infection. The precise timing of infection with these viruses was established by weekly PCR testing. Comprehensive data were collected regarding epidemiologic and biologic risks of acquisition, including detailed behavioral questionnaires, determination of the viral exposure by household contacts, and collection of blood for measurement of virus-specific neutralizing maternal antibodies. Symptoms of illness associated with infection were captured using standardized physical exams and clinical histories, and blood was collected to evaluate the humoral and cellular immune responses to these viruses that are associated with control of viral replication. 

    Another recent focus of our group has been to elucidate the mechanism of action of the HIV protease inhibitor (PI) nelfinavir to inhibit HHV replication, and investigate the drug's potential to prevent and treat HHV-related diseases. We discovered that nelfinavir is able to block in vitro replication of all HHVs tested to date, at concentrations that are achieved in patients taking doses that are FDA-approved for treatment of HIV. This activity is unique to nelfinavir among PIs, and appears to result from effects of nelfinavir on host cell pathways that are required for viral replication, rather than on the virus itself. Interestingly, at least some of these cellular effects also confer nelfinavir's increasingly appreciated antitumor activities. Because nelfinavir is safe for use in humans, we have undertaken a phase 1/2 trial of nelfinavir for the treatment of Kaposi's sarcoma in Africa and the US. In addition, because nelfinavir is also safe during pregnancy, we are testing whether nelfinavir given to HIV-infected women during pregnancy can prevent congenital CMV infection.

    Selected Publications
    Gantt S, Carlsson J, Shetty AK, Seidel KD, Qin X, Mutsvangwa J, Musingwini G, Woelk G, Zijenah LS, Katzenstein DA and Frenkel LM (2008). Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1 shedding but not with mastitis. AIDS 22(12):1453-1460. PMCID: PMC2504751

    Gantt S, Kakuru A, Wald A, Walusansa V, Corey L, Casper C and Orem J (2010). Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children. Pediatr Blood Cancer 54(5):670-674. PMCID: PMC2839022.  

    Micek MA, Blanco AJ, Beck IA, Dross S, Matunha L, Montoya P, Seidel K, Gantt S, Matediane E, Jamisse L, Gloyd S and Frenkel LM (2010). Nevirapine resistance by timing of HIV type 1 infection in infants treated with single-dose nevirapine. Clin Infect Dis 50(10):1405-1414. PMCID: PMC3038662.

    Gantt S, Carlsson J, Ikoma M, Gachelet E, Gray M, Geballe AP, Corey L, Casper C, Lagunoff M and Vieira J (2011). The HIV protease inhibitor nelfinavir inhibits Kaposi's sarcoma-associated herpesvirus replication in vitro. Antimicrob Agents Chemother 55(6):2696-2703. PMCID: PMC3101462.   

    Gantt S and Casper C (2011). Human herpesvirus 8-associated neoplasms: the roles of viral replication and antiviral treatment. Curr Opin Infect Dis 24(4):295-301. PubMed PMID: 21666458

    Gantt S, Payant R, Carlsson J, Micek MA, Blanco AJ, Beck IA, Matunha L, Montoya P, Matediane E, Jamisse L, Gloyd S, and Frenkel LM (2012). Nevirapine-resistant HIV-1 DNA in breast milk after single-dose nevirapine with or without zidovudine for prevention of mother-to-child transmission. J Pediatr Infect Dis Soc. 1 (3): 244-249. 
    PubMed PMID: 23687579.

    Villeneuve D, Brothers A, Harvey E, Kemna M, Law Y, Nemeth T, and Gantt S (2013). Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients. Pediatr Transplant. 17(1): 80–85. Pubmed PMID: 23240598

    Le J and Gantt S (2013). Human Herpesvirus 6, 7 and 8 in solid organ transplantation. Amer J Transplant. Suppl 4:128-37. PubMed PMID: 23465006.  

    Gantt S and Muller WJ (In press). The role of host defenses in neonatal herpes simplex virus infection. Clin Develop Immunol.  

    Gantt S, Huang ML, Magaret A, Bunts L, Selke S, Wald A, Rosenthal PJ, Dorsey G, and Casper C (In press). An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia. J Clin Virol. 
    Grants

    CIHR Operating Grant - Project: "Correlates of acquisition and immune control of primary Epstein-Barr virus infection in Ugandan infants" – 2014-19

    NIH (Co-PIs: Soren Gantt and Serge Barcy) 03/01/11 – 02/29/16

    P01 Project: “Immune Control of KSHV Infection and Impact of HIV Infection And Therapy”

    NIH (PI: Soren Gantt) 03/01/11 – 02/29/16
    P01 Clinical Core: “Oral pathogenesis and host interactions of KSHV infection”

    NIH (PI: Helen Horton) 04/01/12 – 03/31/17
    “Myeloid-derived Suppressor cells (MDSC) suppress infant immune responses”

    NIH/ International Maternal-Pediatric-Adolescent AIDS Clinical Trials Group 
    (Co-PIs: Soren Gantt and Lisa Frenkel) 11/01/12 – 10/31/14
    New Works Concept Sheet 117: “The ability of maternal nelfinavir treatment to prevent congenital cytomegalovirus infection”

    NIH/ UW Institute of Translational Clinical Sciences (PI: Soren Gantt) 06/01/09 – 05/31/10 

    “Activity of HIV Protease Inhibitors on Human Herpesvirus Replication in Vitro” 

    NIH/ Center for AIDS Research (PI: Soren Gantt) 10/01/08 – 09/30/10 
    “Primary Human Herpesvirus 8 Infection in Ugandan Infants” 

    UW/ Royalty Research Fund Award (PI: Soren Gantt) 02/01/10 – 01/31/11 
    “Efficacy of Artesunate to Inhibit Cytomegalovirus Replication In Vivo: A Sub-Study Of Randomized Controlled Trials Of Malaria Treatment In Ugandan Children”

    NIH/ Center for AIDS Research (PI: Soren Gantt) 06/01/09 – 05/31/11
    “Activity of Antiretroviral Drugs on Human Herpesvirus 8 Replication in Vitro” 

    NIH/ Roadmap KL2 Clinical Scholar Training Program (PI: Soren Gantt) 07/01/06 – 06/30/11
    “Primary Human Herpesvirus 8 Infection in Ugandan Children”

    UW/ Virology Division Innovative Research Pilot Award (PI: Soren Gantt) 01/01/11 – 12/31/11
    "Identification of novel drug targets to inhibit human herpesvirus replication using the lead compound nelfinavir"
    Honours & Awards
    • Honors for Undergraduate Research, Brown University, 1993
    • Sigma Xi Society, 1993
    • Rosenbluth Foundation Travel Award, 1999
    • Alpha Omega Alpha Medical Honor Society, 2001
    • The Maurice Freiman Award for Clinical Excellence, 2001
    • Special Alternative Pathway, American Board of Pediatrics, 2002
    • NIH Pediatric Research Loan Repayment Program Award, 2003
    • Young Investigator Award, Conference on Retroviruses & Opportunistic Infections, 2006
    • NIH Roadmap Clinical Research Career Development Program Award, 2006
    • University of Washington Center for AIDS Research New Investigator Award, 2007
    • Letter of commendation from the Chair of Pediatrics, 2013

    Research Group Members