Ernesto Bongarzone

    Email Address:
    College: Medicine Department: Anatomy and Cell Biology
    Title: Professor
    Office: COMRB 9073 Phone: 66894
    Participating in the Chancellor’s Undergraduate Research Awards program: Yes

    Research Interest:
    I have a long-standing interest in the neurobiology of myelination. Myelin is the sheath of apposed membranes that wraps and electrically insulates axons of the central and peripheral nervous systems. Numerous conditions including multiple sclerosis, genetic leukodystrophies, neurodegenerative pathologies, aging and intoxications increase myelin vulnerability, leading to disease, which remains largely incurable. The long-term goal of my research program is to translate our detailed understanding of pathogenic mechanisms of disease into rationalized therapies to cure demyelination. In particular, my laboratory is interested on:

    1) Synergy therapies for genetic leukodystrophies. Demyelinating lysosomal storage orphan diseases such as Krabbe disease (deficiency of Galactosylceramidase) or metachromatic disease (MLD, deficiency of arylsulfatase A) are currently very difficult to treat. Early therapeutic studies performed on mouse models for Krabbe disease and MLD indicated the relevance that the disease phenotype exerts on the outcome of a therapy. Mutant mice with a milder neurological phenotype such as the MLD mice responded positively to gene and cell therapies (Luca et al., 2005; Givogri et al., 2006; Givogri et al., 2008). In contrast, these therapies failed in the severe twitcher mouse, a model for Krabbe disease (Dolcetta et al., 2004; Galbiati et al., 2005; Galbiati et al., 2009). Further experimentation from my laboratory demonstrated the complexity of Krabbe disease, becoming evident that this leukodystrophy is compounded with various additional pathogenic mechanisms, most of them driven by the toxicity of psychosine (the material that is stored in Krabbe disease). With federal and private funding, we are investigating an array of basic cell biology questions including how psychosine affects membrane biogenesis and lipid rafts, axonal cytoskeleton, vesicular axonal transport and neuromuscular junction (White et al., 2009; White et al., 2010; Cantuti et al., 2011, 2012, 2013; Smith et al., 2012; Smith et al., 2014). With these findings, it became obvious that single therapies would fail to cure Krabbe disease. Departing from a better understanding of Krabbe’s pathogenesis, my lab is interested in determining the benefits of combining gene therapy, cell therapy and targeted neuropharmacology. We are interested in determining the best synergic therapies for Krabbe disease resulting from combining different routes of delivery, vectors (adeno-associated viral or lentiviral vectors), donor cells (bone marrow stem cells) and drugs (inhibitors).

    2) Cellular and molecular mechanisms regulating remyelination in disease. My interest to positively treat myelin diseases is complemented with work on remyelination. The demonstration of de novo generation of neural cells (neurogliogenesis) in the adult brain and the presence of adult oligodendrocyte progenitors throughout the CNS provide a unique possibility to study the in vivo behavior and responses of these cells to disease and to identify molecular targets for therapy. Currently, we are characterizing the response of endogenous brain progenitors to viral infection. Our studies use CRISPR cas 9 gene editing, and CRE-recombination transgenesis to look into the role of specific pathways in increasing myelin vulnerability and modifying remyelination.

    Minimum time commitment in hours per week: 15

    Qualifications of a Student:
    Two positions are open to freshman and/or sophomores only. Candidates are expected to dedicate the junior and senior years (2 years) to bench research. GPA>3.65. Prior research experience in lab work is expected, with solid knowledge of stoichiometry, general chemistry/organic chemistry and basics of biology, genetics, and cell biology. The applicant should be able to quickly learn and master new techniques, have excellent communication and team-work skills, be mature, reliable in lab time, and highly organized with lab notes and general activities within the lab. Candidate must be able to devote 15 hours/week during the junior and the senior years and work towards their capstone project.

    Brief Summary of what is expected from the student:
    Candidates shall expect a highly interactive lab environment. Students will be exposed to senior researchers who are prone to share their talents and knowledge. Students are expected to learn from them, being able to follow protocols and techniques with precision, developing multi-tasking and problem solving skills and in time, becoming independent. Real time communication is expected at all times regarding time-off, exams, vacations, etc. Lab time is expected to be devoted to lab activities only. Students should expect to start a training period where they will be under the supervision of a senior technician/researcher/graduate student to learn general lab duties and techniques. After this period and with evidence of gained precision, commitment and trouble-shooting skills, students are expected to become fully embedded in a particular project under the direction of a project leader.

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