You are here: Home / Research / Upcoming Seminars

Upcoming Seminars

Barry J. Byrne M.D., Ph.D. - "Gene Therapy Strategies for Inherited Myopathies"

Child Health Research Institute, UF Powell Gene Therapy Center, University of Florida, College of Medicine, USA
When May 02, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
Add event to calendar vCal
iCal

Short CV

Abstract
Pompe disease results from a deficiency or absence of the lysosomal enzyme acid alpha glucosidase (GAA), resulting in lysosomal accumulation of glycogen which impacts striated muscle and motorneurons.  The weakness observed in patients is a manifestation of the cellular changes which include alterations in the neuromuscular junction (NMJ).  Cardiorespiratory failure is the leading cause of morbidity and mortality in Pompe patients.  We have investigated the utility of AAV vectors expressing GAA to restore lysosomal function in several non-clinical studies a phase I/II study in ventilator-dependent and independent pediatric Pompe patients. In a series of preclinical studies, we have found that restoration of GAA activity in muscle and neural tissue is able to reverse ventilatory insufficiency by reversing motor neuron dysfunction and restoring the integrity of the NMJ.  The principle defect in the motor unit is related to deficiency of NMJ structure and function.  
New evidence also indicates the need for early intervention related to neural dysfunction since motor neurons show evidence of apoptosis in the murine and canine model of Pompe disease.  These deficits are present early in the mouse model and restoration of GAA activity in the muscle and neurons before 6 months of age leads to restoration of in situ force production.  After 18 months of age, the loss in motor neurons leads to permanent deficits in force production of the tibialis anterior.  
Nine children were studied in the first Pompe gene therapy trial and all subjects have undergone one year of follow up.  All children had improvement in spontaneous ventilatory endurance from baseline to the one-year study endpoint.  Additionally, findings related to immune management pave the way to the current clinical studies in adults and younger subjects who are candidates for systemic admiration of a next-generation AAV vector delivered systemically.  The loss of neuromuscular junction formation is a major contributor of weakness and ventilatory failure and these deficits can be prevented by early administration of AAV-GAA which leads to rescue of the CNS deficits.  Current studies utilizing AAV9-GAA are expected to lead to more efficient targeting of muscle and motor neurons following systemic and CNS vector delivery

Gerard Karsenty, M.D., Ph.D. - " The contribution of bone to whole organism physiology"

Department of Genetics and Development, Columbia University Medical Center, New York, USA
When May 14, 2018
from 12:00 PM to 01:30 PM
Where tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
Add event to calendar vCal
iCal

Short CV

Abstract
I have devoted my entire scientific career to the biology of the skeleton. In the study of skeletal development, I along with others have identified Runx2 as the earliest and most specific determinant of osteoblast differentiation. I showed that it is mutated in a frequent human skeletal dysplasia called cleidocranial dysplasia. I identified functions of Runx2 during chondrogenesis, transcription factors interacting with Runx2 and ATF4 as another transcription factor enriched in osteoblasts and acting downstream of Runx2. I also identified Gcm2 as the earliest determinant of parathyroid gland development. In the study of skeletal physiology which is the main focus currently of the lab, I identified a gene inhibiting extracellular matrix mineralization and provided a genetic framework for why extracellular matrix mineralization occurs only in bone and teeth. Most of the current activity in the lab is focused on exploring the hypotheses I proposed 18 years ago that there is a coordinated regulation, endocrine in nature, of bone growth, energy metabolism and reproduction. Testing all aspects of this hypothesis has allowed the lab to reveal the existence of a central control of bone mass and to identify on molecular and genetic grounds how this regulation is achieved. More recently, we have identified the bone-derived hormone osteocalcin has a biologically important regulator of insulin secretion and glucose homeostasis, energy expenditure, testosterone secretion and male fertility. Osteocalcin regulatory functions go beyond the contours define by our original hypothesis and for instance osteocalcin crosses the blood brain barrier and its signaling in the brain is needed for brain development and cognitive functions in adult animals. Osteocalcin signaling in myoblasts is also needed for adaptation to exercise in part because it favors the production of interleukin 6 by muscle. We have identified two receptors for osteocalcin, one mediating its peripheral function and another one mediating its central functions. Currently we are defining a single con conceptual framework that will encompass all the known functions of osteocalcin and are using this framework to identify novel functions of this hormone and altogether to redefine what has been skeletal biology throughout evolution. 

Tullio Pozzan, M.D. - "Ca2+ and cAMP signalling within and around mitochondria"

Director of the Dept. of Biomed. Sciences of the CNR and Full Professor University of Padova
When May 29, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
Add event to calendar vCal
iCal

Short CV

Abstract
A unique and critical feature of signal transduction controlled by soluble second messengers is the convergence of a very large variety of extracellular stimuli onto a very small number of intracellular molecules (Ca2+ and cAMP in particular). Maintenance of signal specificity requires an elaborate signalling code, relying not only on controlled changes in second messenger concentration, but also on their complex spatio-temporal variations. Evidence has accumulated indicating that mitochondria can be regarded as signalling hubs, involving localized changes in the concentration of Ca2+ and cAMP on their surface  and within their matrix. I will discuss the approaches we have employed to selectively monitor Ca2+ and cAMP dynamics in these subcompartments and I will discuss a few novel findings concerning the mechanisms of mitochondrial cAMP microdomain generation and the modulation of  mitochondrial Ca2+ uptake in pathophysiological models. 

Michele De Luca, M.D. - "Life-saving regeneration of the entire human epidermis by transgenic stem cells"

Centre for Regenerative Medicine "Stefano Ferrari", University of Modena and Reggio Emilia, Modena, Italy
When Jun 05, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
Add event to calendar vCal
iCal

Short CV

Abstract
Laminin beta3-deficient generalized Junctional Epidermolyis Bullosa is the first genetic disease targeted by transplantation of epidermal cultures originated from transgenic epidermal stem cells. Three patients were treated with autologous epidermal cultures transduced with a MLV-derived retroviral vector carrying the LAMB3 cDNA under the control of the viral LTR. Several skin biopsies were taken from each patients to perform histological analysis, immunofluorescence, in situ hybridization and genome-wide analysis of the retroviral integration sites. The regenerated epidermis was normal-looking, remained mechanically stable throughout the entire follow-up period and did not form blisters, even upon shear force. We observed a proper expression and location of laminin 332 in the basal lamina. In situ hybridization performed using vector-specific LAMB3 probes showed homogenous expression of LAMB3 mRNA in all epidermal layers, confirming that the regenerated epidermis consists only of transgenic keratinocytes. Histological analysis showed a normal and fully differentiated epidermis with a normal dermal-epidermal junction. Electron Microscopy confirmed the presence of well-defined, organized hemidesmosomes comparable to those of healthy controls. In particular, we report life-saving regeneration of the entire epidermis on a seven-year-old JEB child. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes.

Adriano Aguzzi, MD, Ph.D. - "The Biology of Mammalian Prions"

Institute of Neuropathology, University Hospital of Zürich, Switzerland
When Jun 12, 2018
from 12:00 PM to 01:00 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
Add event to calendar vCal
iCal

Short CV

Abstract
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases of humans and many animal species caused by prions. The main constituent of prions is PrPSc, an aggregated moiety of the host-derived membrane glycolipoprotein PrPC. Prions were found to encipher many phenotypic, genetically stable TSE variants. The latter is very surprising, since PrPC is encoded by the host genome and all prion strains share the same amino acid sequence. Here I will review what is known about the infectivity, the neurotoxicity, and the neuroinvasiveness of prions. Also, I will explain why I regard the prion strain question as a fascinating challenge – with implications that go well beyond prion science. Finally, I will report some recent results obtained in my laboratory, which is attempting to address the strain question and some other basic issues of prion biology with a “systems” approach that utilizes organic chemistry, photophysics, proteomics, and mouse transgenesis.