Cellular and Structural Biology | Faculty
Department of Cellular & Structural Biology

CSB Faculty

 

Photo of Dr. Penalva Luiz Otavio F. Penalva, Ph.D.
Assistant Professor

 

Universidad Autonoma de Madrid, Spain, 1996

 

GCCRI
(210) 562-9049
PENALVA@UTHSCSA.EDU

 

Luiz O.F. Penalva, Ph.D., joined the Greehey Children's Cancer Research Institute in July of 2004 with major faculty responsibilities as a Principal Investigator in Molecular Oncogenesis, Founding Member of the Children's Cancer Research Institute and Assistant Professor in the Department of Cellular and Structural Biology. Dr. Penalva attended the University of Sao Paulo, Brazil and received his Ph.D. from the University of Madrid (UAM), Spain. His post-doctoral work was completed at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and Duke University in Durham, N.C.

 

Dr. Penalva has been honored with fellowships by the Ministry and Science and Education in Spain, the European Molecular Biology Organization, and the Raychem/Rogers/Morrish Fellowship at Duke University.

 

Research:
My laboratory investigates different aspects of post-transcriptional regulation, with a special focus on RNA binding proteins. Our major goal is to understand the participation of these processes in tumorigenesis. We use a variety of approaches that include bioinformatics, genomics, proteomics and molecular biology to characterize the regulatory networks formed by RNA binding proteins and their target RNAs. The main projects of the lab are listed below:

  • We are using SAGE, MPSS and Microarray data to determine the pattern of expression of RNA binding proteins in normal and tumor tissue. The main goal of this project is to identify tissue specific RNA binding proteins and RNA binding proteins that are aberrantly expressed in tumor tissue. The main candidates derived from these lists will be explored as to their participation in tissue/organ development and tumor formation.

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  • The participation of RNA binding proteins in tumorigenesis is poorly understood. There are just a few examples of RNA binding proteins that appear to work as oncogenes. The characterization of RNA binding proteins that are aberrantly expressed in tumors is necessary as an initial step to establish stronger links between RNA binding proteins and tumor formation. Our lab is currently dissecting the participation of the protein Musashi1 in glioblastoma and medulloblastoma formation. A high-throughput analysis was conducted, leading to the identification of 162 new RNA targets. The Gene Ontology analysis indicated that Musashi1 regulates several genes involved in cell cycle, proliferation, apoptosis and differentiation. We have also established that the knockdown of Musashi1 interferes with the ability of medulloblastoma cells to proliferate and form tumors.
    • Research Image 1 - Dr. Penalva Research Image 2 - Dr. Penalva
    Enlarge Musashi1... Image.

     

  • The fate of a given mRNA is determined by elements located on its UTRs. These elements will dictate levels of translation, stability and will be necessary for transport and localization. We are mapping regulatory elements located on UTRs using a combined in silico/in vivo method. We initiated our analysis by identifying short nucleotide sequences (n-mers) that are over-represented in either 5' or 3' UTRs. A given n-mer is considered over-represented if it appears more frequently than its mathematical expected frequency. This strategy has been used successfully to map regulatory sequences in promoters. It is possible that over-represented sequences in UTRs might function as binding sites for RNA binding proteins and non-coding RNAS, functioning thus as regulatory elements. In order to select the best candidates for in vivo validation, we performed cluster and gene ontology analyses of large groups and groups containing 2 or more identical n-mers. In several cases, the analysis indicated strong commonalities amongst members of the same group, suggesting that they in fact belong to the same gene network. Our lab is also part of the ENCODE consortium. We have been using the RIP-Chip method to identify binding sites of specific RNA binding proteins in UTRs. We are currently developing a more robust method using deep sequencing instead of microarrays.
    • Research Image 3 - Dr. Penalva

 

Research Techniques:
Genomics (RIP-chip, RNAseq, microarrays, deep sequencing)
Proteomics
Bioinformatics
Cancer and molecular biology methods

 

PUBLICATIONS:
R. de Sousa Abreu, L. O. F. Penalva, E. M. Marcotte and C. Vogel, (2009) Global signatures of protein and mRNA expression levels. Molecular Biosystems (in press).

 

de Sousa Abreu R, Sanchez-Diaz PC, Vogel C, Burns SC, Ko D, Burton TL, Vo DT, Chennasamudaram S, Le SY, Shapiro BA, Penalva LO. (2009) Genomic analyses of musashi1 downstream targets show a strong association with cancer-related processes. J Biol Chem. 2009 May 1;284(18):12125-35.

 

Galante PA, Sandhu D, de Sousa Abreu R, Gradassi M, Slager N, Vogel C, de Souza SJ, Penalva LO. (2009) A comprehensive in silico expression analysis of RNA binding proteins in normal and tumor tissue: Identification of potential players in tumor formation. RNA Biol. 2009 Oct 24;6(4).

 

Yoon K, Ko D, Doderer M, Livi CB, Penalva LO. (2008) Over-represented sequences located on 3' UTRs are potentially involved in regulatory functions. RNA Biol. 2008 Oct-Dec;5(4):255-62.

 

Sanchez-Diaz PC, Burton TL, Burns SC, Hung JY, Penalva LO. (2008) Musashi1 modulates cell proliferation genes in the medulloblastoma cell line Daoy. BMC Cancer. 2008 Sep 30;8:280.