Address

Barbara Ann Karmanos Cancer Institute Wayne State University School of Medicine 4100 John R, Mail Code: HW05HO Detroit, MI 48201

Department

 Oncology

Research interests

• Glioblstoma (GBM) 
  
• Cancer imaging and therapy ·       
  
• Non-invasive delivery of nanomedcine to the brain

Research description

My research focuses on developing nanoparticles that can cross the blood-brain barrier and target primary glioblastoma multiform (GBM) selectively. My work resulted in the development of a series of new dendrimer-based responsive MRI contrast agents that can be detected by standard MR relaxation methods or Chemical Exchange Saturation Transfer (CEST), and a new MRI method based on Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). In BIRDS the paramagnetically-shifted non-exchangeable protons from the agent are detected with 3D chemical shift imaging (CSI). I developed pH-responsive MRI probes that can be used as potential readouts or metrics for therapy. These are of great interest as there are few prognostic biomarkers available for brain cancer. We developed pH-sensitive BIRDS agents to characterize aggressive malignant gliomas and to monitor early therapy responses in vivo by monitoring extracellular pH noninvasively. We demonstrated that the intravenously administered dendrimer-based agents can traverse pores of the blood-brain tumor barrier of human malignant gliomas. I developed a series of molecular imaging agents for cancer. I have used state-of-the-art MRI methods to study tumor progression and early responses to chemotherapy in pre-clinical animal models. In addition, we developed patient-derived orthotopic xenograft (PDOX) models of GBM with upregulated O6-methylguanine methyltransferase (MGMT). About 50% to 60% of GBM patients do not benefit from the standard-of-care agent temozolomide (TMZ) and radiotherapy (RT). This is because of resistance mediated in large part by the overexpression of MGMT. We developed molecularly targeted MGMT inhibitors from FDA-approved agents and used these to chemically deplete MGMT from a PDOX GBM to overcome TMZ and RT resistance. We reformulated promising anti-cancer drugs that failed to reach clinical trials or failed in clinical trials due to toxicity or poor bioavailability using nanoparticles. These reformulations have provided usable and safe therapies. Success in our studies of preclinical animal tumor models should provide us with novel therapeutic agents and methods that can be further developed for clinical applications.

PubMed - my bibliography

 PubMedAliM

Education/training

1996 M.S.  Mie University, Japan
1999 Ph.D. Mie University, Japan
1999- 2002 Postdoc  University of Texas at Arlington, Arlington, TX
 2002-2005 Research Associate  University of Texas at Dallas, Richardson, TX
2005-2008 Sr. Research Associate  Case Western Reserve University, Cleveland, OH

 

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