SEP 27, 2018 01:30 PM PDT

Cilia Abnormalities and Developmental Defects in Lowe Syndrome

Presented At Cell Biology 2018
C.E. CREDITS: P.A.C.E. CE | Florida CE
Speakers
  • Associate Professor and Assistant Head, Department of Biological Sciences, Purdue University
    Biography
      Dr. Aguilar obtained his PhD degree in Immunochemistry from the School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. Dr. Aguilar pursued his post-doctoral training at the National institutes of Health in Bethesda, MD in the lab of the well-known cell biologist Dr. Juan Bonifacino. In 2005, after a period as Associate Research Scientist at The Johns Hopkins University (in Dr. Beverly Wendland lab), Dr. Aguilar joined the Faculty of the Department of Biological Sciences at Purdue University. There, his group studies the mechanisms linking endocytosis and signaling in health and disease. In order to pursue its research goals, the Aguilar lab routinely use biophysical, biochemical and genetic approaches.

    Abstract:

    Lowe Syndrome (LS) is a devastating genetic disease characterized by abnormalities in the eyes, brain and kidneys that unfortunately leads to the premature death of affected children due to renal failure. Despite being described more than 60 years ago, this condition lacks a clear delineation of its mechanism and no specific cure is available. One contributing cause to this slow progress has been the absence of proper disease models for this condition and the inaccessibility of patient cells from the major affected organs. 

    However, using patient skin fibroblasts we recently reported the first successful preparation of Lowe syndrome induced Pluripotent Stem Cells (iPSCs) and their reprogramming as renal cells1. This work not only represents a technological advance for the LS research field, but also provided insight as to how the patient’s kidney complications develop.

    Specifically, monitoring the process of in vitro kidney cell differentiation provided clues as to how renal deficiency arises in patients. Specifically, we found that in LS kidney cells the transcription factor Six2 (crucial for renal development) was abnormally retained outside the cell nucleus impairing its gene regulatory function. This deficient Six2 activity caused decreased production of the so-called proximal tubular cells which are involved in critical functions of the kidney, such as avoiding the excretion of important serum proteins. 

    Misregulation of a differentiation pathway is a novel LS phenotype that is predicted to have great impact in patients’ renal function. Further, this work suggests that developing strategies directed to enhance proper Six2 function or to prevent its retention outside the nucleus constitute viable options to maintain renal function in LS patients.

    Learning Objectives: 

    1. Understand how Lowe Syndrome can lead to premature death of affected children.
    2. Understand how patient skin fibroblasts are helping those affected with Lowe Syndrome.


    Show Resources
    You May Also Like
    MAY 03, 2018 11:00 AM PDT
    MAY 03, 2018 11:00 AM PDT
    DATE: May 3, 2018TIME: 11:00AM PDT, 2:00PM EDTWhile stress is one of the leading causes of neuropsychiatric disorders, the molecular underpinnings of how stress induces alterations in b...
    APR 27, 2018 10:00 AM PDT
    C.E. CREDITS
    APR 27, 2018 10:00 AM PDT
    DATE: April 27, 2018TIME: 10:00am PST, 1:00pm ESTGlioblastoma (GBM) and Medulloblastoma (MB) are the most common adult and paediatric brain tumours, both of which can have devastating c...
    MAY 22, 2018 08:00 AM PDT
    C.E. CREDITS
    MAY 22, 2018 08:00 AM PDT
    DATE: May 22, 2018TIME: 08:00AM PDT The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that...
    AUG 15, 2018 08:00 AM PDT
    C.E. CREDITS
    AUG 15, 2018 08:00 AM PDT
    DATE: August 15, 2018TIME: 08:00AM PDT, 11:00AM EDTThe failure of current chemotherapeutic strategies in the fight against cancer can be largely attributed to the occurrence of drug res...
    JUN 29, 2018 09:00 AM PDT
    C.E. CREDITS
    JUN 29, 2018 09:00 AM PDT
    DATE: June 29, 2018TIME: 09:00AM PDT, 12:00PM EDT There is significant epidemiological evidence to suggest that the consumption of a high-broccoli diet is associated with a r...
    MAY 29, 2018 09:00 AM PDT
    C.E. CREDITS
    MAY 29, 2018 09:00 AM PDT
    Recent advances in immuno-oncology research has proven the critical role of immune cells in cancer therapy. Deep understanding of the interaction and phenotype of immune and tumor cells withi...
    Loading Comments...