Prof. Kwanghun Chung Receives NIH New Innovator Award

Kwanghun Chung, Samuel A. Goldblith Career Development Assistant Professor in Chemical Engineering at MIT, core faculty member of the Institute for Medical Engineering and Science, core member of the Picower Institute for Learning and Memory, and an Associate member of the Broad Institute, was selected to receive a 2016 NIH New Innovator Award for his project titled “Proteome-Driven Holistic Reconstruction of Organ-Wide Multi-Scale Networks.”

Professor Chung’s research has focused on developing new techniques to produce comprehensive, high-resolution maps of complex organs such as the brain. In his project abstract, Chung proposes “a holistic approach for studying organ-wide functional networks at multiple scales through the development of pioneering technologies that enable proteomic reconstruction of organs at unprecedented resolution.” Current biological methodology requires dividing biological systems into “known cell types and then separately studying each population,” which Chung says can ignore important but unidentified functional networks. With the award, Professor Chung plans to develop technologies that can enable more holistic understanding of these complex biological systems.

The 2016 High-Risk, High-Reward Research awards were given to 88 highly creative and exceptional scientists with bold approaches to major challenges in biomedical research. The awards span the broad mission of the NIH and include groundbreaking research, such as engineering immune cells producing drugs at the site of diseased tissue; developing a sensor to rapidly detect antibiotic resistance of a bacterial infection; understanding how certain parasites evade host detection by continually changing their surface proteins; and developing implants that run off the electricity generated from the motion of a beating the heart.

“The program continues to support high-caliber investigators whose ideas stretch the boundaries of our scientific knowledge,” said NIH Director Francis S. Collins, MD, PhD. “We welcome the newest cohort of outstanding scientists to the program and look forward to their valuable contributions.”

NIH traditionally supports research projects, not individual investigators. However, the HRHR program seeks to identify scientists with ideas that have the potential for high impact, but may be at a stage too early to fare well in the traditional peer review process. These awards encourage creative, outside-the-box thinkers to pursue exciting and innovative ideas in biomedical research.

The High-Risk, High-Reward Research program, part of the NIH Common Fund, manages the following four awards:

The Pioneer Award, established in 2004, challenges investigators at all career levels to pursue new research directions and develop groundbreaking approaches with a high impact on a broad area of biomedical or behavioral science.

The New Innovator Award, established in 2007, supports unusually innovative research from early career investigators who are within 10 years of their terminal degree or clinical residency and have not yet received a research project grant (R01) or equivalent NIH grant.

The Transformative Research Award, established in 2009, promotes cross-cutting, interdisciplinary approaches and is open to individuals and teams of investigators who propose research that could potentially create or challenge existing paradigms.

The Early Independence Award, established in 2011, provides an opportunity for exceptional junior scientists who have recently received their doctoral degree or finished medical residency to skip traditional post-doctoral training and move immediately into independent research positions.

In 2016, the NIH issued 12 Pioneer awards, 48 New Innovator awards, 12 Transformative Research awards, and 16 Early Independence awards. The awards total approximately $127 million and represents contributions from the NIH Common Fund; the National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Environmental Health Sciences; National Institute of General Medical Sciences; National Institute of Mental Health; and the Big Data to Knowledge initiative.

The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.

New Innovator awardee bios and projects can be found here.

MAP technology featured in MIT News

Imaging the brain at multiple size scales

New technique can reveal subcellular details and long-range connections.

Anne Trafton | MIT News Office
July 25, 2016

MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.

This technique, known as magnified analysis of proteome (MAP), should help scientists in their ongoing efforts to chart the connectivity and functions of neurons in the human brain, says Kwanghun Chung, the Samuel A. Goldblith Assistant Professor in the Department of Chemical Engineering, and a member of MIT’s Institute for Medical Engineering and Science (IMES) and Picower Institute for Learning and Memory.

“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything. We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity,” says Chung, the senior author of a paper describing the method in the July 25 issue of Nature Biotechnology.

The researchers also showed that the technique is applicable to other organs such as the heart, lungs, liver, and kidneys.

The paper’s lead authors are postdoc Taeyun Ku, graduate student Justin Swaney, and visiting scholar Jeong-Yoon Park.

MAP paper published in Nature Biotechnology

The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.

Kwanghun Chung receives McKnight Technological Innovations in Neuroscience Award

Kwanghun (KC) Chung, investigator of neuroscience at the Picower Institute for Learning and Memory, core faculty of the Institute for Medical Engineering and Science, and an assistant professor in the MIT departments of Chemical Engineering and Brain and Cognitive Sciences, was selected to receive a 2016 McKnight Technological Innovations in Neuroscience Award for his work on “multi-scale proteomic reconstruction of cells and their brain-wide connectivity.”

Dr. Chung and his lab are developing new technologies to generate a comprehensive, high-resolution brain map, including one known as CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging / Immunostaining / in situ-hybridization-compatible Tissue hYdrogel), which renders tissues, like those within the brain, completely transparent. Chung gained international recognition for creating this breakthrough technology.

Current brain mapping is relatively low resolution and incomplete; Chung’s research will allow neuroscientists to interrogate many molecules, cell types, and circuits in single tissues. By utilizing a transparent brain image and additional biological techniques, an exceptionally detailed map of neuronal pathways can be made which were previously inaccessible.

Dr. Chung is also working to combine new tissue processing technologies with genetic labeling techniques. Chung expanded on the CLARITY technology to develop SWITCH, which uniquely allows for up to 22 different proteins to be imaged in a 3D array. Dr. Chung hopes that this high resolution, comprehensive brain mapping will accelerate the pace of discovery in a broad range of neuroscience applications and enable scientists to characterize animal disease models in a fast and unbiased way.

“I am very grateful about the opportunities that this award will provide,” said Chung. “With the resources we will pursue our high-risk project in developing new technologies for integrated, high-resolution imaging and phenotyping of the brain.”

“It has been a thrill to see the ingenuity at work in developing new neurotechnologies,” said Markus Meister, PhD, chair of the awards committee and the Anne P. and Benjamin F. Biaggini professor of biological sciences at Caltech. “This year’s awards reflect the great untapped potential that still exists in visualizing the connectivity and function of the brain.”

The Endowment Fund predominantly supports work seeking to advance the ability to monitor, manipulate, analyze or model brain function. The awards do not support research based primarily on existing techniques. Technologies developed with McKnight support must ultimately be made available to other scientists.

The McKnight Endowment Fund for Neuroscience will grant $600,000 over two years for the award, with three research projects each receiving $200,000 to expand the range of technologies for studying the brain and its diseases and to make these new technologies available to the field of neuroscience. Since the technology awards began in 1999, the Endowment Fund has contributed more than $12 million to innovative technologies for neuroscience.

The next round of awards will be announced in October, with letters of intent due December 1, 2016. For more information about the awards, please visit https://www.neuroscience.mcknight.org/the-awards/technology.