Michelle L. Matter, PhD

Michelle L. Matter, PhD

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Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Associate Researcher (Associate Professor), University of Hawaiʻi Cancer Center, University of Hawaiʻi at Mānoa
Graduate Faculty, Cell and Molecular Biology, Clinical Research Program, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa
Graduate Faculty, Molecular Biosciences and Bioengineering, University of Hawaiʻi at Mānoa

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

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 reported that Native Hawaiians face a two times higher cancer-associated sepsis mortality rate than any other ethnic group. They are currently investigating ethnicity-related genetic factors of cancer-associated sepsis. Moreover, Dr. Matter has identified that R-Ras binds directly to Filamin A to regulate vascular permeability. Her team is 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's group is investigating PTRH2's physiological function. They have found 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

Matter ML, Shevtsov Y, Dugay C, Haiman CA, Le Marchand L, Wilkens LR, Maskarinec G. (2017). High mortality due to sepsis in Native Hawaiians and African Americans: The Multiethnic Cohort. PLoSONE; May 30;12(5):e0178374. doi: 10.1371/journal.pone.0178374.

Doe J, Kaindl AM, Jijiwa M, de la Vega M, Hu H, Griffiths GS, Fontelonga TM, Barraza P, Van Ry P, Ramos JW, Burkin DJ, Matter ML. (2017). PTRH2 gene mutation causes progressive congenital skeletal muscle pathology. Human Molecular Genetics; Apr 15;26(8):1458-1464. doi: 10.1093/hmg/ddx048.

Sulzmaier FJ, Prechtl A, Caliva MJ, Geerts D, Garmire L, Matter ML, Kesari S, Ramos JW. ((2016). RSK2 regulates glioblastoma invasion and is a promising therapeutic target. Oncotarget; Nov 29;7(48):79869-79884. doi: 10.18632/oncotarget.13084.

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.

Publication list via PubMed