Marzena Lewandowska, PhD
Laboratory of Dr. Ann Harris
Human Molecular Genetics Program
2430 N. Halsted St. Rm C.357
Chicago, IL 60614
MS, August Cieszkowski Agricultural University, Poland
PhD, Open University, UK (reseach component: International Centre of Genetic Engineering and Biotechnology , Trieste, Italy)
1. Downregulation of CFTR gene expression occurs during lung development and it was previously suggested that this down-regulation is dependent on the generation of CFTR transcripts containing alternative 5' exons, which may repress the major CFTR promoter. To evaluate this hypothesis my experiments are designed to answer the following questions: are there any sequences in the CFTR distal promoter region that repress of enhance the major promoter? Does the inclusion of alternative 5' exons inhibit CFTR transcription/translation? In addition, in collaboration with Dr. Marcelo Bento Soares's laboratory we are investigating whether methylation plays a role in CFTR promoter function.
2. Aberrations in the splicing machinery cause or contribute to the development, progression or maintenance of numerous diseases. I'm interested in intronic and exonic variants with unclear functional significance. These represent a diagnostic challenge even if they do not obviously affect gene function.
Pinotti M, Rizzoto L, Balestra D, Lewandowska MA, Cavallari N, Marchetti G, Bernardi F, Pagani F. (2008) U1-snRNA-mediated rescue of mRNA processing in severe factor VII deficiency. Blood, 111: 2681-2684.
Buratti E, Dhir A, Lewandowska MA, Baralle FE. (2007) RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events. Nucleic Acids Research, 35: 4369-4383.
Lewandowska MA, Stuani C, Parvizpur A, Baralle FE, Pagani F. (2005) Functional studies on the ATM intronic splicing processing element. Nucleic Acids Research, 33: 4007-4015.