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SHORT BIOGRAPHIC SKETCH: Dr. Jan Rohozinski is a native of Adelaide, South Australia. He graduated from the University of Adelaide with a Bachelor of Agricultural Science (Honors) degree and subsequently worked on hepatic physiology, pyrophosphate metabolism in wheat grains and sugar cane viruses. Dr. Rohozinski received a Ph.D. in molecular plant virology from the University of Adelaide. He has worked in the field of plant virology in Nebraska, Canberra (Australia), Iowa and Idaho and medical virology at St. Jude Children’s Research Hospital, Memphis, Tennessee. Recently he worked on the genetics and molecular biology of murine and human reproduction and the expression of retrogenes in ovarian cancer at the Baylor College of Medicine, Houston, Texas. He joined the Wake Forest Institute for Regenerative Medicine in October 2006 and continues to pursue interests in ovarian cancer stem cell biology, spermatogenesis and retrogene expression in differentiating cells. SYNOPSIS OF AREA OF INTEREST: The role of testis specific retrogenes and the Y chromosome in male fertility and spermatogenesis. Novel patterns of gene expression in ovarian cancer and the role of stem cells in ovarian cancer biology. DETAILED AREA OF INTEREST: Testis specific retrogenes are a group of autosomal genes that are retrotransposed copies of genes located on the X chromosome that have acquired spermatogenesis specific function. At the time of sexbody formation during meiosis, the sex chromosomes are transcriptionally silenced. Autosomal retrogene copies of genes, present on the X chromosome, that encode essential cell functions are thought to be selected for during spermatogenesis as a mechanism of enhancing male fertility and sperm production. We have identified one such retrogene, Utp14b, that when mutated in mice results in the juvenile spermatogonial depletion (jsd) phenotype which is characterized by azoospermia and complete adult male infertility. Mutation within the human homologue, Utp14c, is associated with cases of azoospermia as well. Currently Dr. Rohozinski is working on identifying the various transcripts of the mouse Utp14b gene that are produced during spermatogenesis. In addition he is raising antibody to the gene product to study its location and function during sperm development. Experiments to determine if the X chromosome gene product can substitute for that of the retrogene are also under way. One of the surprising findings of the work on the human retrogene Utp14c was its expression in the ovary as well as testis but no other human tissue. This led to the hypothesis that this retrogene may also be expressed in ovarian cancers and may provide a suitable marker for early diagnosis and be a suitable target for therapeutic intervention. Recent work has established that Utp14c is expressed in over 90% of ovarian cancers tested to date. In addition to Utp14c there are 14 known testis specific retrogenes in man. Five additional members of this gene family have been tested for expression in ovarian tumors. All were found to be expressed in a high percentage of ovarian tumors. Work is continuing to study the expression of additional members of this gene family and to explore the clinical implications of this discovery. PUBLICATIONS: Rohozinski J, Bishop CE. The mouse juvenile spermatogonial depletion (jsd) phenotype is due to a mutation in the X-derived retrogene, mUtp14b. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11695-700. Rohozinski J, Agoulnik AI, Boettger-Tong HL, Bishop CE. Successful targeting of mouse Y chromosome genes using a site-directed insertion vector. Genesis. 2002 Jan;32(1):1-7. Boettger-Tong HL, Rohozinski J, Agoulnik AI, Dohmae K, Nishimune
Y, Levy N, Bishop CE. Identification and sequencing the juvenile
spermatogonial depletion critical interval on mouse chromosome
1 reveals the presence of eight candidate genes. |
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| 336.713.7293 | regenmed@wfubmc.edu © 2006 Wake Forest Institute for Regenerative Medicine |
Jan
Rohozinski, Ph.D. 