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MOLECULAR MEDICINE




…from bench to bedside

    Marialuisa Lavitrano, PhD
 Professor of Pathology and Immunology
    Head of Molecular Medicine Lab
     Department of Surgical Science
    marialuisa.lavitrano@unimib.it



    University of Milano-Bicocca
Marialuisa Lavitrano - Molecular Medicine Lab
                                                   MEDICINE - BIOTECHNOLOGY




     Research & Training Projecst
                                                           Genomics
                                                                                            B
                                                                                            I
                                                           Proteomics
                                                                                            O
                                                                                            I
                                                                                            N
                                                           Molecular & Cell biology
                                                          cytogenetic, molecular imaging
                                                                                            F
                                                                                            O
                                                                                            R
                                                          Pre-clinical studies
                                                                                            M
                                                                                            A
                                                                                            T
                                                                                            I
                                                           Novel Therapeutic
                                                                                            C
                                                           Applications
                                                                                            S


                                     Links with     Technology platforms       European
                                                                                            SME
                                    EC networks      Trained researchers      regulations



                                                  University of Milano-Bicocca
Marialuisa Lavitrano - Molecular Medicine

                  RESEARCH ACTIVITY
                                                                Preclinical
              Development                 Data-
                            Prevention/            Biological   Experimental
               of disease                 mining
                            Treatment              validation   Medicine
                 model



                   Inflammatory Diseases

                 Ischemia/Riperfusion Injury

                      Transplantation
…from bench                                            …to bedside
                   Cardiovascular Diseases

                    Neurological Disorders


                            Cancer



                  University of Milano-Bicocca
Production of Transgenic animals - SMGT technology in mice

  SMGT:

      1989
      Sperm cells as vectors for introducing foreign
      DNA into eggs: genetic transformation of mice.
      Lavitrano M. et al Cell; 57: 717-723.




                      University of Milano-Bicocca
Production of Transgenic animals - SMGT technology in pigs

  SMGT:
  2002
 Efficient production by sperm-mediated gene transfer of
 human decay accelerating factor (hDAF) transgenic pigs
 for xenotransplantation.
 Lavitrano M. et al. Proc Natl Acad Sci U S A. 2002 Oct 29;99 (22):14230-5




                     University of Milano-Bicocca
Animal models to study rejection in transplantation

  2007
  Reduction of hyperacute rejection and protection of
  metabolism and function in hearts of human decay
  accelerating factor (hDAF)-expressing pigs.
  Smolenski et al Cardiovasc. Res. 2007, 73(1):143-52




                          University of Milano-Bicocca
Production of Transgenic animals - SMGT technology in pigs

 SMGT: Multi-transgenic pigs
 2003
 Piglets add some colors to transgenic story. Nature, 424:624
 2005
 Multi-transgenic pigs expressing three fluorescent proteins
 produced with high efficiency by sperm mediated gene transfer.
 Webster et al. Mol Reprod Dev. 72: 68-76

                                                              Green filter
                                                              Blue filter
                                                              Red filter




                                                      Wide range filter
    Light microscope


                       University of Milano-Bicocca
Production of Transgenic animals - SMGT technology in pigs




                 University of Milano-Bicocca
Production of Transgenic animals - SMGT technology in pigs

SMGT: Transgenic pigs

2006


 non-viral
 episomal
 Vector




       Manzini et al Proc Natl Acad Sci U S A. 2006, 21;103(47):17672-7
                     University of Milano-Bicocca
Production of Transgenic animals - Neurological disorders

  SMGT:

   2007
   Early glial dysfunction in absence of neurodegeneration in
   a Spinocerebellar Ataxia Type 1 transgenic model
   Giovannoni et al Neuron Glia Biology 3, p335-351.


             Conditional Transgenesis
             Canzoniere et al., J Neuosci, 2004
                           al., Neuosci,




                          University of Milano-Bicocca
Ischemia Reperfusion Injury: protective role of CO


 2004
 Carbon monoxide improves cardiac energetics and
 safeguards the heart during reperfusion after
 cardiopulmonary bypass in pigs.
 Lavitrano et al. FASEB J. 2004 Jul;18(10):1093-5.




                          University of Milano-Bicocca
Atherosclerosis: plaque prevention

  2006
  Indication for carotid endarterectomy versus carotid
  stenting for the prevention of brain embolization
  from carotid artery plaques: in search of consensus.
  Biasi et al J Endovasc Ther. 2006 Oct;13(5):578-91




                         University of Milano-Bicocca
Aneurysm: gene expression profiling

  2009
  Gene Expression Profiling of Peripheral Blood in Patients
  with Abdominal Aortic Aneurysm.
  Giusti et al Eur J Vasc Endovasc Surg. 2009




                         University of Milano-Bicocca
Molecular Medicine Lab - Milano Bicocca




         University of Milano-Bicocca
Animal Facilities & Surgical Theatre




       University of Milano-Bicocca

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Molecular medicine

  • 1. MOLECULAR MEDICINE …from bench to bedside Marialuisa Lavitrano, PhD Professor of Pathology and Immunology Head of Molecular Medicine Lab Department of Surgical Science marialuisa.lavitrano@unimib.it University of Milano-Bicocca
  • 2. Marialuisa Lavitrano - Molecular Medicine Lab MEDICINE - BIOTECHNOLOGY Research & Training Projecst Genomics B I Proteomics O I N Molecular & Cell biology cytogenetic, molecular imaging F O R Pre-clinical studies M A T I Novel Therapeutic C Applications S Links with Technology platforms European SME EC networks Trained researchers regulations University of Milano-Bicocca
  • 3. Marialuisa Lavitrano - Molecular Medicine RESEARCH ACTIVITY Preclinical Development Data- Prevention/ Biological Experimental of disease mining Treatment validation Medicine model Inflammatory Diseases Ischemia/Riperfusion Injury Transplantation …from bench …to bedside Cardiovascular Diseases Neurological Disorders Cancer University of Milano-Bicocca
  • 4. Production of Transgenic animals - SMGT technology in mice SMGT: 1989 Sperm cells as vectors for introducing foreign DNA into eggs: genetic transformation of mice. Lavitrano M. et al Cell; 57: 717-723. University of Milano-Bicocca
  • 5. Production of Transgenic animals - SMGT technology in pigs SMGT: 2002 Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation. Lavitrano M. et al. Proc Natl Acad Sci U S A. 2002 Oct 29;99 (22):14230-5 University of Milano-Bicocca
  • 6. Animal models to study rejection in transplantation 2007 Reduction of hyperacute rejection and protection of metabolism and function in hearts of human decay accelerating factor (hDAF)-expressing pigs. Smolenski et al Cardiovasc. Res. 2007, 73(1):143-52 University of Milano-Bicocca
  • 7. Production of Transgenic animals - SMGT technology in pigs SMGT: Multi-transgenic pigs 2003 Piglets add some colors to transgenic story. Nature, 424:624 2005 Multi-transgenic pigs expressing three fluorescent proteins produced with high efficiency by sperm mediated gene transfer. Webster et al. Mol Reprod Dev. 72: 68-76 Green filter Blue filter Red filter Wide range filter Light microscope University of Milano-Bicocca
  • 8. Production of Transgenic animals - SMGT technology in pigs University of Milano-Bicocca
  • 9. Production of Transgenic animals - SMGT technology in pigs SMGT: Transgenic pigs 2006 non-viral episomal Vector Manzini et al Proc Natl Acad Sci U S A. 2006, 21;103(47):17672-7 University of Milano-Bicocca
  • 10. Production of Transgenic animals - Neurological disorders SMGT: 2007 Early glial dysfunction in absence of neurodegeneration in a Spinocerebellar Ataxia Type 1 transgenic model Giovannoni et al Neuron Glia Biology 3, p335-351. Conditional Transgenesis Canzoniere et al., J Neuosci, 2004 al., Neuosci, University of Milano-Bicocca
  • 11. Ischemia Reperfusion Injury: protective role of CO 2004 Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. Lavitrano et al. FASEB J. 2004 Jul;18(10):1093-5. University of Milano-Bicocca
  • 12. Atherosclerosis: plaque prevention 2006 Indication for carotid endarterectomy versus carotid stenting for the prevention of brain embolization from carotid artery plaques: in search of consensus. Biasi et al J Endovasc Ther. 2006 Oct;13(5):578-91 University of Milano-Bicocca
  • 13. Aneurysm: gene expression profiling 2009 Gene Expression Profiling of Peripheral Blood in Patients with Abdominal Aortic Aneurysm. Giusti et al Eur J Vasc Endovasc Surg. 2009 University of Milano-Bicocca
  • 14. Molecular Medicine Lab - Milano Bicocca University of Milano-Bicocca
  • 15. Animal Facilities & Surgical Theatre University of Milano-Bicocca