The Department Appoints New Laboratory Director
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| Hanna Rennert, PhD | |
Dr. Rennert is developing Molecular Pathology services for genetics, virology, oncology and identity testing, and introducing automated platforms for different testing steps. The Molecular Pathology Laboratory recently validated and is now performing HCV genotyping, in addition to the HCV Viral Load test already offered cystic fibrosis mutation testing, bone marrow engraftment analysis and viral load testing related to transplantation will be developed as part of the expansion of molecular services. Dr. Rennert is also working with Roche Diagnostics to introduce their new FDA approved HIV-1 molecular diagnostic test system. This system is the first PCR-based test offering automated specimen preparation followed by automated amplification and quantification of HIV-1 RNA for viral load monitoring. This will greatly enhance patient care by increasing testing reliability and decreasing turn-around time.
Dr. Rennert’s research focuses on understanding the genetic components contributing to the complex, multifactorial etiology of prostate cancer, and understanding the disparity in prostate cancer incidence among different ethnic populations. She became interested in this topic several years ago while directing the Research and Development Microarray Laboratory at the Genetic Institute of Tel Aviv Sourasky Medical Center, in Tel Aviv, Israel.
During this time she studied genetic changes associated with solid tumors and the genetic factors that predispose Israeli Jews to prostate cancer. She identified a novel truncating mutation in the enzyme 2’-5’- oligoadenylate-dependent RNase L (RNASEL), which was associated with prostate cancer risk in Ashkenazi Jews.
Dr. Rennert has continued these studies in the United States, using a multidisciplinary approach that combines methods from epidemiology, biostatistics, molecular biology, and classic genetics for studying prostate cancer. Her research subsequently focused on two promising molecular markers, RNASEL and macrophage scavenger receptor 1 (MSR1). These genes play a major role in inflammatory processes and were identified as candidate inherited susceptibility genes for familial prostate cancer. Using high throughput genotyping techniques, she has studied 16 different single nucleotide polymorphisms (SNPs) in these genes reported to be associated with prostate cancer risk in a large population of African-American and European-American case-control subjects seen at the University of Pennsylvania Health System. Certain SNPs in RNASEL and MSR1 are associated with prostate cancer characteristics (Gleason grade and TNM stage) by family history and by ethnic group. Moreover, haplotype analysis of MSR1 SNPs with frequency above >5% in either sample study demonstrates that certain SNPs have a combined protective effect on prostate cancer severity, and that patients with advanced disease are less likely to carry these haplotypes.
Ethnic background, in addition to family history and age, is a major risk factor for prostate cancer. The incidence of clinical prostate cancer is highest among African-American men and is strikingly low in native Asians. To determine the role of these genes in the disparity of prostate cancer incidence between highrisk and low-risk populations, Dr. Rennert has established a collaboration with the Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India. Preliminary studies in Asian Indians have identified a new spectrum of sequence variants in these genes, including a new deleterious mutation in RNASEL. This mutation is estimated to be present in about 1% of the Asian-Indian population.
Dr. Rennert’s interest in the genetics of disease extends beyond prostate cancer. A second research interest is exploring the role of RNASEL in programmed cell death (apoptosis) in normal peripheral blood lymphocytes and in HIV-infected cells. RNASEL is a constitutively expressed latent endonuclease that mediates the antiviral and proapoptotic activities of the interferon-inducible 2-5A system. The depletion of CD4+ T cells during human HIV-1 infection has been attributed to several mechanisms including apoptosis. Increased expression of RNASEL in Jurkat cells, for example, was shown to suppress HIV-1 replication by 8-fold. The role of RNASEL in lymphocyte function has not been extensively studied. However, Dr. Rennert has studied the expression of RNASEL in peripheral blood cells from normal individuals. Preliminary results show that RNASEL is differentially expressed among the different blood cell types, and that its expression is significantly higher in granulocytes than all other cell types. This finding is in line with the role of RNASEL as an antiviral and antibacterial gene by causing RNA degradation and inhibition of cell growth. Her current research is investigating whether RNASEL expression levels in peripheral blood lymphocytes are indeed induced by HIV-1 infection, and whether this is associated with CD4+ T cell depletion.
A third research interest is focused on the development of molecular diagnostic assays and applications for clinical use. As a scientist with the Molecular Pathology Laboratory at University of Pennsylvania she was involved in the development of many assays, including RT-PCR for t(15;17), gene dosage analysis for spinal muscular atrophy carrier testing, and short tandem repeats (STR) analysis for monitoring allogeneic bone marrow engraftment. Her current efforts as the Director of the Molecular Pathology Laboratory at NewYork-Presbyterian Hospital are geared towards expanding the Laboratory test menu, particularly in the fields of virology, genetics, and identity testing. This includes the development and implementation of quantification assays for the herpes virus panel using real time PCR, cystic fibrosis testing and STR analysis for monitoring engraftment following bone marrow transplantation. Dr. Rennert welcomes questions about her research and about particular molecular tests that may be relevant to your patients. She can be contacted at 746-6412.
