![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Division of Intramural Research
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Overview |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Organizational Chart |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Research Branches
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Research Investigators Profiles, publications, links |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Clinical Research
Clinical trials, patient recruitment, IRB, FAQ, Overview |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
NHGRI Affiliated Centers CIDR, NCGC, NISC
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Online Research Resources Developed at NHGRI
Databases, software, tools, more. |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Division of Intramural Research Calendar
Workshops, conferences, seminar series, courses, more. |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
Books and Publications |
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
In Other Sections:
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/leftnav/navbottom_research.gif) |
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/leftnav/navright2_research.gif) |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif)
![Marjan Huizing](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/People/huizingm.jpg) |
Marjan Huizing, Ph.D.
Associate Investigator
Medical Genetics Branch
Head
Cell Biology of Metabolic Disorders Unit
B.Sc. Wageningen University,
Netherlands, 1990
M.Sc. Wageningen University, Netherlands, 1992
Ph.D. Nijmegen University, Netherlands, 1998
|
|
Dr. Huizing's laboratory investigates rare human genetic disorders and normal and abnormal intracellular processes, with the goal of gaining insight into changes in molecular function that underlie various genetic metabolic disorders and developing treatments for these illnesses. Her research focuses on hereditary inclusion body myopathy (HIBM) and Hermansky-Pudlak syndrome.
HIBM is caused by mutations in the gene encoding the enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase. Defects in this enzyme, which catalyzes two committed steps in sialic acid biosynthesis, cause sialic acid deficiency. Without new supplies of sialic acid, progressive muscle degeneration, or myopathy, sets in. The typical course of the disease involves a steady deterioration of arm and leg muscles until, eventually, patients are unable to walk.
Sialic acid is a negatively charged sugar localized at the end of glycoconjugate chains on glycoproteins and glycolipids. These chains are expressed at the cell surface and are crucial for many biological processes, including cell adhesion and signal transduction. Research has shown that dystroglycan, an integral component of the muscle transmembrane dystrophinglycoprotein complex, is involved in the pathogenesis of many forms of myopathy, including muscular dystrophy. Dr. Huizing's group demonstrated that muscle α-dystroglycan in patients with HIBM is low in sialic acid. They are now investigating the use of N-acetyl-mannosamine (ManNAc), a neutral sugar and specific substrate for sialic acid synthesis, as a therapy for HIBM; they also are developing a mouse model for testing such a therapy. Another treatment involves infusing mice with immunoglobulin, which is high in sialic acid content.
Dr. Huizing also studies other sialic acid-related diseases, including sialuria, a progressive disease in which patients produce too much sialic acid. Symptoms may include developmental delay, coarse features, and enlargement of the liver. Sialuria appears to be caused by a single mutation that causes a change in the three-dimensional structure of the active site of the enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase. A third sialic acid-related disease, infantile free sialic acid storage disease, involves a transport malfunction that causes sialic acid to accumulate in lysosomes.
In addition, Dr. Huizing is investigating the causes of and potential treatments for Hermansky-Pudlak syndrome (HPS), a rare inherited disorder that has been identified in about 400 people worldwide. Affected individuals are characterized by decreased pigmentation (ocular or cutaneous albinism), a lack of platelet dense bodies (causing bleeding problems), and their storage of an abnormal fat-protein compound, called ceroid, which leads to dysfunction in some organs. The disease can cause prolonged bleeding and poor function of the lungs and intestine; fatal pulmonary fibrosis also is a possible complication. An ongoing clinical trial at NHGRI is testing the drug pirfenidone as a potential HPS treatment. The purpose of the trial is to find out whether pirfenidone can relieve symptoms associated with pulmonary fibrosis.
Dr. Huizing's group continues to look for additional HPS-causing genes, with the hopes of better understanding the biology of the disease. She played a major role in identifying seven distinct genetic subgroups of HPS patients, cataloguing relevant clinical and genetic characteristics. She also helped discover the mutated gene associated with the HPS-3 subgroup. Scientists subsequently discovered several other HPS-related genetic mutations in mice. To study the effects of HPS mutations, Dr. Huizing's group is using fluorescent protein expression studies to examine the defective intracellular trafficking to lysosome-related organelles in HPS patients' cells. It has been shown that such cells fail to transport certain lysosomal proteins to their correct destination, and HPS gene products somehow are involved in recognizing specialized vesicles key to lysosomal biogenesis.
Last Updated: June 9, 2008
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif)
|
![](https://webarchive.library.unt.edu/web/20080916050045im_/http://genome.gov/Images/spacer2.gif) |