Funding/ Grants

NIH R01-NS091552: Unruptured Intracranial Aneurysms: Ruputure-risk Assessment by Non-invasive Molecular Imaging

Project Period: 2015-2019

A large number of people in the USA live with silent brain aneurysms that are being increasingly discovered by imaging procedures. Rupture of brain aneurysms causes about 30,000 people in US to develop hemorrhagic strokes each year, many of whom will die unnecessarily. There is strong evidence suggesting that the development of aneurysms involves several steps, including endothelial activation. Large numbers of neutrophils carrying primary myeloperoxidase (MPO)-rich granules are the first responders to local endothelial activation resulting in a downstream infiltration of monocytes. We have discovered that there is an association between MPO in human aneurysms with known risk factors for rupture (Gounis MJ, et al. Stroke 45:1474-7, 2014). We have developed a strategy for contrast-assisted magnetic resonance imaging (MRI) of MPO activity in vitro and in vivo (Chen JW et al. Radiology 2006 240:473-81) using the effect of enzyme-mediated MR signal amplification (MRamp) (Bogdanov A Jr. et al. Mol Imaging. 2002 1:16-23). In this research we propose to optimize these new contrast agents for non-invasive MRI-based imaging that will allow clinicians to follow the presence of molecules that will indicate the likelihood that an aneurysm will burst. The resulting diagnostic MRI –based imaging method is likely to spare patients from unnecessary surgery and save lives.

NIH R01-DK095728:  Molecular Fluorescence Lifetime Sensor of Pro-Inflammatory Signaling in Diabetes

Project Period:  2014-2018

The goal is to develop improved methods for the early diagnosis of Type I and Type II diabetes in order to afford greater clinical success with early detection, intervention, and ultimately prevention of the disease. The strategy involves the non-invasive imaging and detection of early changes in functional NF-kB, a transcription factor activated early in the disease process that is responsible for initiating signaling cascades that ultimately result in pancreatic inflammation and subsequent destruction of insulin-secreting β-cells. 

NIH R01-EB000858:  MR Signal Amplification for Receptor Imaging

Project Period: 2013 – 2017

The goal is to continue our research aimed at developing and validating novel imaging probes which can be applied to detection of in vivo changes in EGFR expression in bone metastases of mammary adenocarcinoma (MAC) using MRI (high resolution) and µPET (high sensitivity) techniques. This work is expected to be readily translatable to the design of a new diagnostic capability (monitoring levels of EGFR/EpCAM expression). MRamp is one of the few available techniques that allows detection of the co-expression of two protein markers (receptors). This work will also provide a new experimental tool for clinical and preclinical investigations regarding the etiology and pathology of metastatic adenocarcinoma.

NIH R21-EB017980: Engineering of Multi-functional Nucleolin-targeted Nucleic Acid Delivery System

Project Period 2013 – 2015

We propose to design, construct, and test an oligonucleotide (ODN) duplex/gold nanoparticle (GNP) chimera that will improve the delivery and the antitumor efficacy of therapeutic nucleic acid constructs. Specifically, our proposed GNP-based system will deliver a therapeutic STAT3d payload capable of selectively inhibiting the proliferation of tumor cells that depend on STAT3 constitutive expression.

NIH R21-AI108529: A Bilateral Collaborative Research Partnership: Optimization and In Vivo Testing of a Novel Combination Microbicide

Project Period 2014 – 2016.

In collaboration with Dr Gottikh (Moscow State University), Dr. Grainer (UMass Chan) and Dr. Celia Schiffer (UMass Chan), we propose to establish a partnership for testing novel NNRT/NRTI formulations using CCR5/CXCR4 reporters. We will determine the efficacy of a topical microbicide formulation in a humanized mouse model.