Big Ideas, Small Features: Utilizing Advanced Microscopic and Nanoscale Technologies to Further Human Healthcare

Principal Investigator: Elena Aikawa, MD. Brigham and Women’s Hospital

Calcific aortic valve disease (CAVD) claims 17,000 lives in the US alone, annually. No drug- based therapy is available. The only effective treatment is invasive and costly aortic valve replacement for late-stage disease patients. This study will use a novel 3D-bioprinted model of CAVD and an innovative drug-delivery platform to elucidate the underlying mechanisms of CAVD and identify potential therapeutic targets.

Principal Investigator: Giorgio Bonmassar, PhD, Massachusetts General Hospital

This project proposes to use the technology available at the Center for Nanoscale Systems (CNS) to design, fabricate, and test nanoscale coil structures for the next generation of µMS devices. Such devices could become potentially the pacemakers and brain stimulators of the future with their contactless ability to deliver the neuronal stimulation.

Principal Investigator: David Frank, MD, PhD, Dana-Farber Cancer Institute

Continuing advances are being made in the development of novel therapies for cancer. However, the ability to target anti-cancer drugs directly to tumor tissue remains a significant unmet need. A unique drug delivery system, known as layer-by-layer (LbL) nanoparticles, has been developed in the laboratory. These LbL nanoparticles are able to deliver drugs with high efficiency to cells. However, it is difficult to characterize the delivery characteristics of the LbL nanoparticles to tumors. We propose to package distinct fluorophores in the layers of LbL nanoparticles of diverse design and using the advanced microscopic technologies at HCBI to quantitate the delivery to tumor model systems. These experiments will have significant translational implications, and will provide insight into basic properties of cancer cell membranes.

Principal Investigator: James Kirby, MD, Beth Israel Deaconess Medical Center

Antibiotic resistance is compromising our ability to treat bacterial infections. Clinical microbiology laboratories guide appropriate treatment through antimicrobial susceptibility testing (AST) of patient isolates. The laboratory has developed an inkjet, digital dispensing technology as a novel platform to perform reference AST for any antimicrobial. This proposal aims to use the expertise at HCBI/IDAC to develop a method for microscopic imaging of bacterial replication in AST format and also verify the performance of the new assay using well-characterized clinical isolates. 

Principal Investigator : Eric Mazur, PhD, Harvard School of Engineering and Applied Sciences

This proposal will 1) investigate how our laser-activated intracellular delivery technique affects living cells and 2) to deliver genome-editing biomolecules to living cells for human health-care applications. Our laboratory has pioneered the use of laser-activated micropyramids that absorb light and generate microbubbles to porate the cell membrane, allowing membrane-impermeable macromolecules to diffuse into the cell. This grant will enable the group to combine our current nanofabrication and cell culture research at CNS with advanced imaging at HCBI to investigate cellular response and to deliver genome-editing tools to living cells using this technique. 

Principal Investigator: Daniel Needleman, PhD, Harvard University Faculty of Arts and Sciences

Mitochondrial dysfunction has long been associated with reduced reproductive potential. More than 200 publications link mitochondrial function with in vitro fertilization (IVF) success. 67% of all IVF cycles fail, making the process economically and emotionally costly to patients and the health system. Non-invasive assessment of mitochondrial health could provide the means for embryo selection.  We have established that we can non-invasively assess mitochondrial function of oocytes by measuring NADH and FAD fluorescence using Fluorescence Lifetime Imaging Microscopy (FLIM), furthermore the Needleman Lab, has demonstrated the safety of 2-photon FLIM for use in oocytes and embryos. The aim of this proposed research is to assess the safety and feasibility of a 1-photon FLIM system for generating FLIM measurements of NADH and FAD.

Principal Investigator: William Shih, PhD, Dana-Farber Cancer Institute

It would be enormously useful towards personalized medicine to be able to screen tumor biopsies by imaging them for thousands of biomolecular markers simultaneously, as this would enable rapid and cost-effective characterization of the tumor. We propose a strategy that offers both compact labels and rapid decoding of potentially thousands of distinct “colors”: molecular barcodes that encode their “colors” (i.e. unique identities) based on prescribed blinking patterns, kind of like a molecular Morse code. For this pilot grant, we propose to image cells and tissues using state-of-the-art instruments at the Harvard Center for Biological Imaging, such as FAST confocal and light-sheet fluorescence microscopes.

Principal Investigator: Johnathan Whetstine, PhD, Massachusetts General Hospital

Genome instability and drug resistance are hallmark features of cancer. We have recently uncovered the first enzyme KDM4A capable of generating transient site-specific copy gains of regions linked to drug resistance and hard to treat cancer, which provides a novel tool to carefully interrogate the molecular features affiliated with copy gains. In this application, we are developing methods to characterize the genomic features associated with copy amplification. The hope is that the combination of the molecular insights gained from this pilot study combined with the microfluidic DNA sorting technology will enable the broad dissemination of these assays such that site-specific copy gains can be used to inform clinical designs and help improve patient outcomes.