Hartwell Foundation Provides Grant for Investigation into "Knifeless" Surgery
The Hartwell Foundation awarded three University of Michigan researchers with a three-year $850k+ grant for their investigation into "knifeless" surgery for the treatment of the pediatric heart defect, hypoplastic left heart syndrome (HLHS). The University provided the trio with matching funds to help carry out their work.

Charles Cain, Ph.D., 2007 Hartwell Investigator and professor of Biomedical Engineering, Gabe Owens, M.D., Ph.D., assistant professor of Pediatric Cardiology, and Zhen Xu, Ph.D., assistant professor of Biomedical Engineering, are the recipients of the grant and will work to gather pre-clinical data in preparation for a human clinical trial on infants with HLHS.

In HLHS, normal blood flow during fetal development is obstructed. Abnormal flow through the fetal heart results in an underdeveloped left ventricle and a heart incapable of pumping oxygenated blood out to the body.

Ideally, intervening early on patients with HLHS may improve outcomes and possibly prevent the development of this fatal condition. However, current neonatal and in utero approaches are challenging, suboptimal, and could be detrimental to both mother and child. To find an alternative solution, Cain, Owens and Xu developed technology to establish proof-of-principle for "knifeless" surgery based on Cain's ultrasound innovation he called histotripsy. Here, high-intensity sound pulses form bubbles within the tissue and act as "mini-scalpels" to cut precise channels for the blood to flow. The treatment focuses on one specific area and the probe sits outside the body.

Hypothetically, creating a channel in an abnormal heart in early fetal development would allow the heart to develop so that HLHS never fully occurs. The three investigators have gathered preliminary data to support a proof-of-principle and plan to inaugurate this technique on newborns with HLHS by the end of the three-year grant. Once successful in newborns, they plan to use this innovative technology for in utero therapies. The Hartwell Foundation seeks to inspire innovation and achievement by providing financial support to biomedical research and discovery that can potentially benefit children. Commitments by the University of Michigan to provide matching funds and substantial infrastructure to sustain an eventual clinical trial of "knifeless" surgery enabled early-stage support from the Foundation.

The University of Michigan is a Hartwell Foundation Top Ten Center of Biomedical Research.

Story credit: Salmiyeh Karamali, U-M Foundation Relations

U-M Funds Collaborative Projects with Research-Led MCubed Seed Grants
At the University of Michigan Medical School, Cory Hogaboam, Ph.D., studies the body's immune responses, including how they factor in lung disease. A few miles away at the College of Engineering, Professor Andre Boehman's field is fuel and internal combustion systems. Now, thanks to a unique new program, they'll be teaming up to study the health effects of nanoparticles like the ones car and truck engines emit.

Hogaboam and Boehman are a part of MCubed, a research funding program at the U-M that lets faculty themselves decide which projects to pursue. A formal, external review isn't part of the process. To qualify for "cube" funding, three researchers from at least two disciplines simply have to agree to work together on a new project.

U-M officials recently announced the first 50 projects to receive $60,000 seed grants in phase one of the program, with 50 faculty from the Medical School collaborating. The two-year pilot, comprised of $15 million from the U-M Provost and participating departments, will give out 200 more early-stage grants soon, in an effort to jumpstart innovative, interdisciplinary work.

Hogaboam and Boehman's team will examine whether nanoscale soot from kitchen gas stoves is harmful to lungs. They'll also be collaborating with Ann Marie LeVine, M.D., an associate professor of pediatrics.

An important but understudied health issue, chronic exposure to soot nanoparticles both in and out of the home could lead to asthma, cancer and even increase the risk of coronary artery disease, LeVine says. She appreciates the opportunity to study it through MCubed.

"The university understands the changing environment in science as well restrictions in funding due to the economy," LeVine said. "U-M is at the forefront working to enhance collaborations across disciplines which has not been done in the past."

It's at these boundaries where big breakthroughs happen, university officials say.

Researchers in surgery and dentistry are exploring a cancer stem cell vaccine. A physicist, an artist and a composer are creating a multimedia event inspired by dark energy. A social scientist, a geriatrician and an architect will investigate what features in cities make it easier or more difficult for older pedestrians to get around. Two teams of engineers and environmental scientists are looking into whether hydraulic fracturing could contaminate drinking water.

Researchers across campus are grateful for the chance to explore some of their most innovative ideas.

Jun Hee Lee, M.D., an assistant professor of molecular and integrative physiology at the Medical School, is working with a biologist and an internal medicine doctor to understand molecular processes that make exercise beneficial. In a pilot study on fruit flies, they'll also explore whether a synthetic protein could provide some of those benefits.

"This concept is in a very early development stage, so pursuing this project can be very risky," Lee said. "Successful completion of this pilot research program would increase our chances of getting traditional funding in the future."

That's the hope of Mark Burns, T.C. Chang Professor of Engineering, professor of chemical engineering and biomedical engineering and chair of the MCubed executive committee. MCubed, Burns says, could be a spark like a small grant was for him and an interdisciplinary team more than a decade ago. In a pilot study, he and his team demonstrated DNA analysis on a chip. The study led to $1.3-million National Science Foundation grant, a Science paper with more than 1,000 citations and a startup, HandyLab, which sold to BD for $275 million. And it has enabled quick diagnostic tests for diseases such as tuberculosis and the flu.

"MCubed essentially eliminates many of the hurdles to funding that faculty members typically have to think about. They don't have to fit the project into the topic of a recent call for proposals, or worry about how their work fits within the confines of a particular funding agency's target topics. They can just focus on the impact of the work," Burns said.

"U-M is known for it's large-scale, interdisciplinary research," notes Steven L. Kunkel, Senior Associate Dean for Research at the Medical School. "MCubed allows our faculty the chance to collaborate on smaller projects outside the mainstream that wouldn't otherwise find funding. We're counting on the concept that sometimes with great risks come great rewards for our patients."

Story credit: Nicole Casal Moore, U-M News Service

New Era in Metabolomics at the University of Michigan
The University of Michigan Health System has earned a $9.1 million core grant from the National Institutes of Health to improve disease diagnosis through metabolic profiling.

With the support, the U-M will create the Michigan Regional Comprehensive Metabolomics Research Core, one of only three centers in the country that will help researchers examine small molecules called metabolites to detect changes in cell behavior and organ function.

The sum of all metabolites at any given moment -- the metabolome -- is a form of chemical readout of the state of health of the cell or body and provides a wealth of information about nutrition, infection, health and disease status.

From diagnosis to disease follow-up, metabolomics may transform the ability to understand the mechanisms underlying disease and help investigators develop new strategies for treatment.

"Physicians and scientists around the world are beginning to realize that metabolic profiling will have a significant impact on the diagnosis, prevention and monitoring of many diseases," says Charles Burant, M.D., Ph.D., director of the Michigan Metabolomics and Obesity Center, and the Dr. Robert C. and Veronica Atkins Professor of Metabolism at the U-M (pictured above).

Burant who is experienced in metabolomics, diabetes and obesity research is the principal investigator of the grant, with Stephen Brown, Ph.D., serving as program coordinator of the new regional metabolomics research core. Several University of Michigan investigators will lead additional components of the core including Robert Kennedy, Ph.D., Hobart H. Willard Professor of Chemistry; Subramanian Pennathur, M.B.B.S., associate professor of internal medicine; Brian Athey, Ph.D., chair of the Department of Computational Medicine and Bioinformatics; Naisyn Wang, Ph.D., professor of statistics, and Barbara Mirel, Ph.D., associate research scientist at the School of Education. Grace Wu will serve as administrator.

It's hoped metabolomics will provide a path to personalized medicine, by offering insights into detection, prevention and treatment of a variety of diseases, including cancer, cardiovascular diseases and diabetes based on a patient's metabolic profile.

Over the next five years, the NIH expects to invest more than $51.4 million nationwide to accelerate metabolomics research.

The first round of NIH funding creates the three regional comprehensive metabolomics research cores. Others are at University of California-Davis and Research Triangle Institute in Research Triangle Park, N.C.

"This research initiative includes data-sharing and coordination with other metabolomics centers and researchers to develop standards for quality metabolomics work," says Brown, the program coordinator. "This will be a critical step as the discipline grows."

The NIH Common Fund is taking a comprehensive approach to boosting the field by funding a variety of initiatives, including training, technology development, standards synthesis, and data-sharing capability.

It's a shared goal of the U-M which will vastly enhance its research capacity in metabolomics with a planned expansion to the North Campus Research Complex. The Complex will serve as a hub for metabolomics research on campus, where proximity of metabolomics researchers is expected to enhance collaboration and speed basic research into better patient care.

The U-M's resource core will provide researchers nationwide with the expertise and infrastructure for metabolomics research, in addition to training opportunities.

Agilent Technologies and Human Metabolome Technologies will partner with the U-M on metabolic profiling instruments and software that can measure hundreds to thousands of unique metabolites.

Story credit: Shantell Kirkendoll, UMHS PRMC