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Faculty

Michelle L. Matter, PhD

Michelle L. Matter, PhD
  • Associate Researcher (Associate Professor)
    and Full Member

    Cancer Biology Program
    University of Hawaii Cancer Center
  • Academic Appointments

  • Graduate Faculty
    Cell and Molecular Biology, Clinical Research Program
    John A. Burns School of Medicine
    University of Hawaii at Manoa
  • Graduate Faculty
    Molecular Biosciences and Bioengineering
    University of Hawaii at Manoa

Degrees

  • PhD in Cell Biology, University of Virginia Medical School
  • Postdoctoral Fellow in Dr. Erkki Ruoslahti's lab at The Sanford Burnham Institute

Research Focus

The objective of the Matter laboratory is to understand the molecular mechanism of cancer metastasis and to develop novel targeted cancer therapeutics. The lab is focused on two areas of metastasis. Vascular permeability is extremely important in metastasis because solid tumors release factors that induce hyperpermeability, which contributes to metastatic spread and limits the ability of targeted delivery of anticancer agents. In addition, induction of vascular permeability is a primary component of the life-threatening disorder sepsis, which causes 10% of cancer patient deaths each year in the United States. Clinically there are no treatments for sepsis. Dr. Matter and her team have identified a novel mechanism by which the regulation of vascular permeability is dependent upon active R-Ras (a GTP-binding protein) and an association between R-Ras and the cytoskeletal protein Filamin A (FLNa). They are investigating how the R-Ras-FLNa complex regulates vascular permeability and testing R-Ras as a potential target in both anti-metastatic and anti-sepsis therapies.

The second area of focus is on molecular mechanisms of cancer cell death. Dr. Matter's work has shown that in normal and cancer cells peptidyl-tRNA hydrolase 2 (PTRH2; Bit-1) controls integrin-mediated apoptosis by regulating the anti-apoptotic protein Bcl-2 through effects of NFkB signaling. Loss of PTRH-2 protein expression promotes apoptosis. Dr. Matter and colleagues reported that patients with a biallelic mutation in the PTRH2 gene, which causes a loss of PTRH2 protein expression, develop infantile-onset multisystem neurologic, endocrine and pancreatic disease (IMNEPD). In contrast, high PTRH2 protein expression promotes tumor cell survival. Dr. Matter and her team find that high PTRH2 levels in neuroblastoma patients correlates with very poor prognosis and increased bone metastasis. PTRH2 is similarly upregulated in other metastatic cancers including melanoma, colon carcinoma and invasive breast ductal carcinoma. Her team is currently identifying the molecular mechanism whereby PTRH2 promotes tumor cell survival and determining if PTRH2 is an effective therapeutic target.

Selected Publications

  • Griffiths GS, Doe J, Jijiwa M, Ramos JW, Burkin DJ, Matter ML. (2015). Bit-1 is a regulator of myogenic differentiation. Journal of Cell Science. 128:1707-1717 doi:10.1242/jcs.
  • Matter ML, Hu H, I-J L, Jijiwa M, Dramer N, Musante L, Ninnemann O, Schindler D, Eirich K, Schrotter S, et al. (2014). Peptidyl-tRNA Hydrolase 2 gene mutation causes infantile multisystem neurologic, endocrine and pancreatic disease. Journal of Clinical and Translational Neurology, Dec;1(12):1024-35. doi: 10.1002/acn3.149.
  • Anastasiadis P, Jojica KDA, Allen JS, Matter ML. (2014). Detection and quantification of bacterial biofilms combining high-frequency acoustic microscopy and targeted lipid microparticles. Journal of Nanobiotechnology,12(1):24. doi: 10.1186/1477-3155-12-24.
  • Griffiths GS, Grundl M, Leychenko A, Reiter S, Young-Robbins SS, Sulzmaier FJ, Caliva MJ, Ramos JW, Matter ML. (2011). Bit-1 is required for integrin-mediated cell survival through activation of the NFkB pathway. Journal of Biological Chemistry, 286:1471-14723.
  • Griffiths GS, Grundl M, Allen JS III, Matter ML. (2011). R-Ras interacts with Filamin A to maintain endothelial barrier function. Journal Cellular Physiology, Sep;226(9):2287-96. doi: 10.1002/jcp.22565.

Publication list via PubMed

Active Grants

  • M. Matter, Principal Investigator
    NIH/NIGMS R01GM104984-01
    "Regulation of endothelial permeability in sepsis"
    2012-2017
  • M. Matter, Principal Investigator
    Myra W & Jean Kent Angus Foundation 04798-0002
    "The role of Bit-1 in neuroblastoma"
    2013-2016