My major contributions have been in the area of translational research involving viral infections in transplant recipients with a focus on molecular evaluation of cytomegalovirus (CMV), molecular diagnostics, clinical pathogenesis and preventative strategies for CMV and other viruses post-transplant:
1. Cytomegalovirus (CMV): We have published seminal studies evaluating molecular and immunological monitoring of CMV in transplant recipients. These include viral load testing for disease prediction (AJT 2004, 2005) and several studies assessing antiviral therapy and prophylaxis (AJT 2004,2005,2007, 2009, 2010). These are among the largest reported studies assessing these issues in high-risk organ transplant recipients. This and the work below resulted in research awards from the American Society of Transplantation and The (International) Transplantation Society. We have also published important work on humoral and cellular host response and CMV prediction (AJT 2005; AJT 2009, Transplantation 2012, CID 2013). Overall, our work on CMV has been instrumental in the development of recent international guidelines for the management of CMV in transplant recipients (International Transplantation Society consensus guidelines - Humar senior author Transplantation 2013; 2013 AST guidelines - Humar senior author AJT 2013). Recently, we have published on the role of interferon-λ and CMV infection (In Press JID).
2. Viral Virulence Factors: This work includes novel assessment of CMV immune evasion gene profiling (Transplantation 2007) and other virologic determinants of CMV including viral polymorphisms and virulence (JCV 2002; JID 2003, CID 2009, Antivir Ther 2009, Transplant ID 2012, Plos One 2012). These include large studies using multicenter sample repositories from transplant patients with CMV disease [Transplantation 2011]. We demonstrated that patients with simultaneous mixed viral strains have delayed clearance kinetics and poorer response to therapy.
3. Novel Herpesviruses: Using molecular surveillance techniques, we have assessed the clinical impact of human herpesvirus 6 (HHV-6) in liver transplant recipients (Transplantation. 2002) and interactions between HHV-6 replication and CMV replication (JID 2000, 2005, Transplantation 2002, 2009). We published one of the largest studies assessing Hepatitis C and HHV-6/7 interactions (Liver Transpl 2007) and the largest study of HHV6/7 co-infection in patients with CMV (AJT 2009 - featured as one of the year's top papers ICAAC 2009). The latter study was performed using an international sample repository from patients with CMV disease (PI A Humar).
4. Emerging Viral Infections: We published one of the first reports of WNV and SARS in transplant patients (AJT 2003; Transplantation 2004). We also performed the first WNV seroprevalence study in transplant patients (>800 patients) and were the first to demonstrate higher rates of severe neurological disease (AJT 2004). We published the largest study of H1N1 in transplant patients (AST multicenter study; Lancet ID 2010; A Humar senior author; D Kumar first author); plenary abstract ATC 2010.
5. Vaccination Studies: We have performed several studies on vaccine evaluation in transplant recipients including pneumococcal and influenza vaccines (AJT 2013, CID 2007, 2008, Plos One 2011). These have been important in developing international guidelines for vaccination in transplant patients (AJT 2013).
1. Cytomegalovirus (CMV): We have published seminal studies evaluating molecular and immunological monitoring of CMV in transplant recipients. These include viral load testing for disease prediction (AJT 2004, 2005) and several studies assessing antiviral therapy and prophylaxis (AJT 2004,2005,2007, 2009, 2010). These are among the largest reported studies assessing these issues in high-risk organ transplant recipients. This and the work below resulted in research awards from the American Society of Transplantation and The (International) Transplantation Society. We have also published important work on humoral and cellular host response and CMV prediction (AJT 2005; AJT 2009, Transplantation 2012, CID 2013). Overall, our work on CMV has been instrumental in the development of recent international guidelines for the management of CMV in transplant recipients (International Transplantation Society consensus guidelines - Humar senior author Transplantation 2013; 2013 AST guidelines - Humar senior author AJT 2013). Recently, we have published on the role of interferon-λ and CMV infection (In Press JID).
2. Viral Virulence Factors: This work includes novel assessment of CMV immune evasion gene profiling (Transplantation 2007) and other virologic determinants of CMV including viral polymorphisms and virulence (JCV 2002; JID 2003, CID 2009, Antivir Ther 2009, Transplant ID 2012, Plos One 2012). These include large studies using multicenter sample repositories from transplant patients with CMV disease [Transplantation 2011]. We demonstrated that patients with simultaneous mixed viral strains have delayed clearance kinetics and poorer response to therapy.
3. Novel Herpesviruses: Using molecular surveillance techniques, we have assessed the clinical impact of human herpesvirus 6 (HHV-6) in liver transplant recipients (Transplantation. 2002) and interactions between HHV-6 replication and CMV replication (JID 2000, 2005, Transplantation 2002, 2009). We published one of the largest studies assessing Hepatitis C and HHV-6/7 interactions (Liver Transpl 2007) and the largest study of HHV6/7 co-infection in patients with CMV (AJT 2009 - featured as one of the year's top papers ICAAC 2009). The latter study was performed using an international sample repository from patients with CMV disease (PI A Humar).
4. Emerging Viral Infections: We published one of the first reports of WNV and SARS in transplant patients (AJT 2003; Transplantation 2004). We also performed the first WNV seroprevalence study in transplant patients (>800 patients) and were the first to demonstrate higher rates of severe neurological disease (AJT 2004). We published the largest study of H1N1 in transplant patients (AST multicenter study; Lancet ID 2010; A Humar senior author; D Kumar first author); plenary abstract ATC 2010.
5. Vaccination Studies: We have performed several studies on vaccine evaluation in transplant recipients including pneumococcal and influenza vaccines (AJT 2013, CID 2007, 2008, Plos One 2011). These have been important in developing international guidelines for vaccination in transplant patients (AJT 2013).