BIMS Affiliated Research Faculty

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Prabhakara  P.  Reddi
Degree(s): PhD
Graduate School: National Institute of Immunology
Primary Appointment: Associate Professor, Pathology
Research Interests:
Transcriptional Regulation of Mammalian Spermatogenesis
Website: http://www.healthsystem.virginia.edu/internet/pathology/RotationOpps/reddilab.cfm
Email Address: ppr5s@virginia.edu

Biomedical Sciences Graduate Program(s)
  • Biomedical Sciences Graduate Programs

  • Research Description

    The ability of each cell to selectively express a distinct set of genes under specific external stimuli is central to cellular differentiation and organogenesis, and a loss of this ability leads to diseases such as cancer. My laboratory utilizes mammalian spermatogenesis as a model system for cellular differentiation and seeks to understand the mechanisms involved in cell-specific gene transcription.

    Sperm, unlike other cells in the human body, contain very unique structures such as the acrosome and the flagellum and the expression of genes encoding the acrosomal and flagellar proteins signals the terminal differentiation of male germ cells. One goal in the laboratory is to identify the master transcription factors responsible for spermatid-specific gene expression. A second goal is to understand the mechanisms which prevent the expression of the spermatid-specific genes in somatic tissues. Using transgenic mice as a model organism and the gene encoding the acrosomal protein SP-10 as a model gene, we gained some insights into the regulation of spermatid-specific gene expression and identified TDP-43, PURalpha and Musashi as transcription factors important for this process. Our work also identified an insulator with enhancer-blocking properties, which likely plays a role in preventing the expression of the spermatid-specific SP-10 gene in somatic tissues. Currently, we are focusing on understanding the biology of TDP-43, PURalpha and Musashi proteins in the testis and the mechanism by which they orchestrate spermatid-specific gene expression. Interestingly, aberrant expression of these proteins has been shown to be associated with certain types of cancer, indicating their critical roles in normal cellular function.

    The outcome of these studies will contribute to a better understanding of mammalian spermatogenesis at the molecular level and will have clinical significance. Today, the incidence of infertility is about 15% and in greater than 80% of male infertility cases, the cause of infertility is unknown (idiopathic). We anticipate that our studies will lead to a better prognosis of male infertility. Further, regulatory factors, which are critical for the completion of spermatogenesis, offer potential targets for the development of novel male contraceptives.


    Selected Publications
  • Reddi PP, Urekar CJ, Abhyankar MM, Ranpura SA. Role of an insulator in testis-specific gene transcription. Ann N Y Acad Sci. 2007 Dec;1120:95-103. Review.
  • Ranpura SA, Deshmukh U, Reddi PP. NF45 and NF90 in murine seminiferous epithelium: potential role in SP-10 gene transcription. J Androl. 2008 Mar-Apr;29(2):186-97. Epub 2007 Oct 17.
  • Abhyankar MM, Urekar C, Reddi PP. A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues: role for TDP-43 in insulator function. J Biol Chem. 2007 Dec 14;282(50):36143-54.
  • Acharya KK, Govind CK, Shore AN, Stoler MH, Reddi PP. cis-requirement for the maintenance of round spermatid-specific transcription. Dev Biol. 2006 Jul 15;295(2):781-90.
  • PubMed Listings for this Faculty Member

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