Andrew D. Yurochko, Ph.D.

Member, CCDS Board of Directors
Ph.D., Immunology – Macrophage Biology, 1990, Virginia Tech Contact Information:
Department of Microbiology
1501 Kings Highway
LSU Health Sciences Center
Shreveport, LA 71130
Office Phone: 318-675-8332
Laboratory Phone: 318-675-8331
Office Fax: 318-675-5764

Major Research Interests: Mechanisms of Human Cytomegalovirus Dissemination and Pathogenesis. (I) We are examining the biological events in human monocytes following HCMV infection because of the critical role these cells play in viral dissemination and the ensuing pathogenesis in AIDS and transplant patients, as well as congenitally infected infants, where HCMV is the leading infectious cause of birth defects. We are addressing from a molecular standpoint, how viral infection of monocytes forces these cells to serve as Trojan Horses for viral spread from the blood into peripheral tissues and then as a source of long-term viral persistence in these tissues. We showed that HCMV specifically activates monocytes and induces monocyte-to-macrophage differentiation and that these viral-induced macrophages become permissive for viral replication, suggesting that HCMV utilizes a novel mechanism for viral dissemination and persistence. Future studies include the examination of the mechanisms responsible for the viral-directed differentiation of monocytes, as well as the functional changes that occur in infected macrophages. (II) HCMV is also a primary viral candidate in the etiology of atherosclerosis, as evidence links HCMV infection to the development and severity of atherosclerotic disease. The cells associated with disease pathology (endothelial cells, monocytes, and smooth muscle cells) are primary in vivo targets for the virus. Endothelial cells line blood vessels, separating blood from the vessel wall; they provide a non-thrombogenic layer, make key cytokines and growth factors, and are the first cells to be altered/damaged during disease progression. We now have the evidence that direct HCMV infection of endothelial cells induces proliferation, migration, and tubular morphogenesis in the infected endothelial cells, all hallmarks of angiogenesis. Future studies will examine the mechanisms by which HCMV infection of endothelial cells promotes a pro-angiogenic environment.

Ongoing cardiovascular-related projects:

1. Analysis of HCMV Infection of Monocytes and Macrophages.
Brief Description: To investigate the molecular biology of HCMV infection of monocytes and macrophages and how this infection results in a cellular differentiation that promotes viral dissemination, persistence and disease (CVDs and disease in immunocompromised indivdiuals).
Names of collaborators / collaborating institutions: None
Funding source: NIH

2. The Regulation of STAT1 in HCMV-Infected Monocytes.
Brief description: To examine the role that STAT1 plays in HCMV-infected monocyte survival and differentiation and how those changes influence the pro-inflammatory state of the infected cell.
Names of collaborators / collaborating institutions: Ms. Emily Stevenson.
Funding source: American Heart Association.

3. The Role of Bcl-2 Family Proteins in Survival & Differentiation of HCMV-infected Monocytes.
Brief description: To examine the how HCMV alters the survival of infected monocytes through a unique regulation of the Bcl-2 family of proteins.
Names of collaborators / collaborating institutions: Ms. Donna Collins-McMillen.
Funding source: Malcolm Feist Cardiovascular Research Fellowship.

4. The Investigation of the Unique Biology of HCMV infection of Monocytes.
Brief description: To examine how the viral modulation of the infected monocyte influences the viral infection process.
Names of collaborators / collaborating institutions: Dr. Jung Heon Kim
Funding source: Malcolm Feist Cardiovascular Research Fellowship

Planned cardiovascular-related projects:

  1. Human cytomegalovirus infection is a strong risk factor in the development of cardiovascular diseases through its the infection and alteration of the biology of blood monocytes, vascular endothelial cells and smooth muscle cells. We have been examining how viral persistence and the strategies the virus utilizes for infection of human hosts links infection to viral pathogenesis.
  2. The investigation of how the viral strategy of infection of monocytes and endothelial cells impacts viral persistence and disease.
  3. The determination of how infection of blood monocytes results in a polarized highly inflammatory cell type.
  4. The investigation of how viral-induced differentiation creates long-lived lipid containing macrophages.
  5. The regulation of viral-induced signaling pathways in altered monocyte and endothelial cell biology.
  6. Bioinformatics based meta-analyses of pro-inflammatory monocytes and macrophages.

Methods and Available Resources:

  • We have nearly 25 years experience working with human peripheral blood monocytes and other human immune cells. We also work with a number of other human cells including various primary endothelial cells and endothelial cell lines. We have developed numerous techniques to manipulate and modify these human cells including various transfection tools for inserting DNA and siRNA into primary human cells. We have pioneered many aspects of host-pathogen interactions and have been addressing basic cell biology, immunology, virology and viral induced pathogenesis. In addition, to the multiple areas of cellular and molecular biology, we have also established a bioinformatics based system to analyze viral pathogenesis in small scale and meta-analyses.
  • Human blood cell isolation and culture.
  • Monocyte biological assays.
  • Endothelial cell biological assays.
  • Immunological assays.
  • BSL pathogen handling.
  • Modern molecular and cellular biological techniques.
  • siRNA based transfection/knockdown in human monocytes.
  • Global transcriptome and bioinformatics based analyses.