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Viral Pathogenesis
 At Children's our studies of viruses as causes of human diseases include both infectious diseases clinical research (HIV/AIDS program) and more basic studies of the growth of human herpesviruses (human cytomegalovirus). Pharmacokinetics and clinical studies of antiviral and antibacterial agents represent a major effort, as part of the Pediatric AIDS Clinical Trials Group (PACTG) and the Adolescent Trials Network (ATN). These programs, under the direction of Hans M.L. Spiegel, MD, PhD, and Larry D’Angelo, MD, have received substantial NIH funding for this work. The Center is testing efficacy of new antiviral agents, with more than 20 open experimental protocols for treatment or observation of HIV positive children and adolescents. The infectious diseases laboratories also focus on the farmacokinetics, safety and efficacy of antibiotics in collaboration with Stephen Soldin, PhD, in our GCRC Bioanalytic Core Laboratory and our newly NIH-funded Pediatric Pharmacology Research Unit. Nalini Singh, MD, MBBS, is using molecular diagnostics and studying microbial resistance. Tamara A. Rakusan, MD, PhD, is studying the epidemiology of adherence to treatment protocols in HIV patients.
While major strides have been made in the prevention and treatment of its diseases, HCMV continues to be a major cause of morbidity in immunosuppressed patients. Human cytomegalovirus (HCMV) infections are a well-described complication of allogeneic transplantation and one that, despite significant advances in prophylactic therapy and pre-emptive treatment, continues to result in significant morbidity and mortality following bone marrow transplantation. Recent evidence also suggests that HCMV infection contributes to the development of malignant glioma. Further, HCMV DNA load is a more reliable negative survival predictor for patients with advanced AIDS than HIV RNA load is. There are more than 8,000 live births with symptomatic HCMV infections in the United States and HCMV is the leading non-genetic cause of hearing loss in children less than 5 years of age. This underscores the need to understand the regulation and the roles of the gene products of HCMV during viral growth.
The goals of the Viral Pathogenesis Program (Anamaris M. Colberg-Poley, PhD) are to understand how HCMV infection alters cellular post-transcriptional RNA processing machineries to finely tune production of selected viral products and to examine the mechanistic basis for the unconventional trafficking, processing and functional role(s) of the predominant UL37 proteins during HCMV infection. This involves studying the processing of HCMV pre-mRNAs and how HCMV infection rapidly alters cellular RNA processing machineries within the host cell. Their studies will test whether HCMV UL37 proteins are trafficking from the endoplasmic reticulum through a novel pathway to mitochondria, which could provide novel targets for rational design of new anti-HCMV treatments.
For more information contact:
Anamaris Colberg-Poley, PhD
Children's Research Institute
Center for Cancer and Immunology Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-3984
202-476-3929 fax
acolberg@cnmc.org
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