Philadelphia University + Thomas Jefferson University
Sidney Kimmel Medical College
Department of Dermatology & Cutaneous Biology

Chu, Mon-li

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Mon-Li H. Chu, PhD

Contact Dr. Chu

Bluemle Life Sciences Building, Room 410
233 South Tenth Street
Philadelphia, PA 19107

(215) 503-4834

Research and Clinical Interests

Our laboratory is engaged in elucidating the structure and function of extracellular matrix proteins and their roles in pathological conditions using a combination of molecular, biochemical, and genetic approaches. The current research activities are focused on two major areas.

The first area involves type VI collagen, which is the major component of beaded microfibrils found in almost all connective tissues. Recessive and dominant mutations in the three collagen VI genes lead to two specific types of congenital muscle disorders: the severe Ullrich congenital muscular dystrophy (UCMD) and the relatively mild Bethlem myopathy (BM). Patients afflicted with both disorders display muscle weakness accompanied by connective tissue abnormalities, including proximal joint contractures and distal joint hyperextensibility. Children with severe UCMD may never walk independently and they develop serious respiratory deficiencies, leading to death in the first and second decades of life. While BM follows a dominant inheritance the severe UCMD phenotype can result from either recessive or dominant mutations. Our laboratory is currently studying the molecular, biochemical and pathological mechanisms underlying type VI collagen gene mutations in BM and UCMD. The consequences of collagen VI mutations are investigated using fibroblasts from BM and UCMD patients. The pathophysiology of collagen VI mutations is investigated by analyzing gene targeted mouse models.

The second area involves fibulins, a family of extracellular matrix proteins that share a homologous carboxyl terminal globular domain preceded by tandem arrays of calcium-binding epidermal growth factor-like modules. The family members are found in a variety of tissues in association with diverse supramolecular structures, including elastic fibers, fibronectin microfibrils, basement membrane networks, and proteoglycan aggregates. Interestingly, most, if not all, fibulins are intimately associated with elastic fibers, and in particular, fibulin-4 and fibulin-5 play essential roles in elastic fiber assembly. Recent studies have associated defects in several fibulins with a range of human diseases, including cutis laxa, cancer, and both inherited and age-related forms of macular degeneration. However, the precise roles of most fibulins in normal and pathological conditions are still largely unknown. Our laboratory is studying the role of fibulins, with an emphasis on the elastic fiber organization, through analyses of gene-targeted mice deficient in one or more fibulins.

Keywords

Antibody Formation; Basement Membrane; Biochemistry; Cell Biology; Chimeric Protein; Collagen; Collagen Disorder; Complementary DNA; Computer Assisted Sequence Analysis; Developmental Biology; Developmental Genetics; Elastic Fiber; Extracellular Matrix Protein; Fibulin; Fluorescence Microscopy; Fusion Gene; Gel Electrophoresis; Gene Expression; Gene Mutation; Genetic Mapping; Genetic Promoter Element; Genetic Regulatory Element; Genetic Technique; Genetics; Human Genetic Material Tag; Human Physiology; Human Subject; Human Tissue; In Situ Hybridization; Laboratory Mouse; Messenger RNA; Molecular Cloning; Northern Blotting; Nucleic Acid Sequence; Pharmacology; Polymerase Chain Reaction; Protein Isoform; Protein Sequence; Protein Structure Function; Recombinant Protein; RNA Splicing; Southern Blotting; Synthetic Peptide; Tissue Cell Culture; Transcription Factor; Transfection; Transgenic Animal; Western Blotting

Publications

Most Recent Peer-Reviewed Publications

  1. Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa
  2. Forelimb contractures and abnormal tendon collagen fibrillogenesis in fibulin-4 null mice
  3. A mouse model for dominant collagen VI disorders Heterozygous Deletion of Col6a3 EXON 16
  4. Human adipose-derived stem cell transplantation as a potential therapy for collagen VI-related congenital muscular dystrophy
  5. Fibulin-2 deficiency attenuates angiotensin II-induced cardiac hypertrophy by reducing transforming growth factor-β signalling
  6. Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin α3β1 in the epidermis
  7. Clinical Significance of Serum COL6A3 in Pancreatic Ductal Adenocarcinoma
  8. COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy
  9. Loss of fibulin-2 protects against progressive ventricular dysfunction after myocardial infarction
  10. Tumor-specific expression and alternative splicing of the COL6A3 gene in pancreatic cancer
  11. Dysfunctional tendon collagen fibrillogenesis in collagen VI null mice
  12. Recessive COL6A2 C-globular missense mutations in Ullrich congenital muscular dystrophy: Role of the C2a splice variant
  13. Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury
  14. Latent transforming growth factor β-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites
  15. Retinoic acid receptors are required for skeletal growth, matrix homeostasis and growth plate function in postnatal mouse
  16. Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance
  17. Muscle interstitial fibroblasts are the main source of collagen VI synthesis in skeletal muscle: Implications for congenital muscular dystrophy types Ullrich and Bethlem
  18. Fibulin-2 is dispensable for mouse development and elastic fiber formation
  19. Biological Role of Fibulin-2 in Cardiovascular Development
  20. Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa