Interdisciplinary Collaboration Drives Novel Research
The Cornell BME department’s collaborative and open culture accelerates the pace of innovation and invention, leading the way to better health and new discoveries. The BME department has many ties with faculty at Weill Cornell Medical College across multiple departments, both academic and clinical. All the first year BME Ph.D. students spend a summer at Weill Cornell in the Immersion Program, working with physicians and seeing patients. In addition, Cornell provides institutional support for new collaborations in seed grants and hosts retreats attended by both engineers and physicians to talk about medical innovation. Such connections lead to interdisciplinary ideas that are targeted towards critical problems in healthcare. Since its founding, the BME department has had a long standing relationship with the Hospital for Special Surgery (HSS). Cornell biomedical engineers Larry Bonassar and David Putnam have partnered with Dr. Scott Rodeo, an orthopaedic surgeon at HSS, to test new new lubricants for articular cartilage. These lubricants are polymer brushes that mimic the structure of the native lubricant on the cartilage surface and have shown the ability to prevent the progression of cartilage damage after joint injury in animals. Led by Michael Shuler and Barbara Hempstead (Hematology and Medical Oncology at Weill Cornell Medical College), the partnership between physicians and engineers was recognized with the creation of the Cornell University Center on the Microenvironment and Metastasis, a Physical Sciences Oncology Center funded by the National Cancer Institute.
Working across fields also leads to new technologies and new applications. At Cornell, one doesn’t have to go far to find the diversity in expertise necessary for breakthroughs. Chris Xu (Applied & Engineering Physics, BME Field Member) and Chris Schaffer (BME)—who like to call themselves Chris2—have joined up with Joe Fetcho (Neurobiology and Behavior) to combine optics and neuroscience to study how running speed is controlled by spinal cord circuits. Mice run on treadmills while neural activity from their spinal cord cells is recorded by a multiphoton microscope using optical activity indicators. This would not be possible without the combination of new, record-breaking, multiphoton microscopes from the engineers and sophisticated understanding of the nervous system from neuroscientists.
Mechanical links between breast cancer and obesity
Obesity increases the risk of breast cancer, but why and whether this can be reversed is not known. Claudia Fischbach-Teschl works with a team from both Ithaca and Weill Cornell on how inflammation and poor tissue oxygenation from obesity creates an environment favorable for breast cancer cells. Fischbach-Teschl studied how fat cells interact with aspects of their environment such as signals from other cells and mechanic cues. Obesity can cause changes such as increasing the stiffness of the extracellular matrix, the scaffolding which hold cells together. Stiff environments have been shown to promote the aggressiveness of estrogen-receptor positive breast cancers. This insight on how being overweight could link to cancer came to Fischbach-Teschl when she heard a talk on inflammation in obesity from Andrew Dannenberg the Henry R. Erle, M.D., Roberts Family Professor of Medicine at Weill Cornell Medical College. A conversation led to long-lasting collaboration including a graduate student. The team expanded to include physician Cliff Hudis, Chief of the Breast Cancer Medicine Service at Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Cornell who provides access to patient samples and a clinical perspective. In addition to contributing a medical perspective the Weill collaborators also helped reach out to other investigators and increase scientific exchange. “The awarded Physical Sciences Oncology Center grant solidified many of these connections and built a network of researchers that are driving cancer research in new directions.” says Fischbach-Teschl.
The clinical importance and the novelty of the Fischbach-Teschl’s approaches were recently recognized with the award of a $1.34 million grant from the National Cancer Institute under the “Provocative Questions” initiative. The “Provocative Questions” identified 20 aspects of cancer which are thought to be crucial for the understanding of this disease. In addition to Dannenberg and Hudis, this collaborative grant also taps into the expertise of Delphine Gourdon, (Materials Science and Engineering, BME Field Member) who works on the role of mechanobiology in disease with physics and material engineering perspectives. Gourdon and Fischbach-Teschl are another example of the productivity of interdisciplinary combinations—their complimentary expertise has resulted in five publications in the last several years. Rebecca Williams, research scientist in BME and director of Cornell’s Biotechnology Resource Center Imaging Facility, rounds out the award team by providing unparalleled imaging technologies.
Engineers address Alzheimer’s disease
Interdisciplinary collaborations also reach across the globe. A partnership between faculty from Cornell BME, Chris Schaffer and Nozomi Nishimura, Weill Cornell Medical College faculty member Costantino Iadecola, and Centre National de la Recherche Scientifique (France) faculty member Sylvie Lorthois, addresses the puzzling link between Alzheimer’s disease (AD) and blood flow. AD is the leading cause of dementia in the U.S. AD cost the U.S. $214 billion in 2014 and the number of patients is projected to increase as the baby boomer generation ages. Physicians have long known that blood flow in the brain is reduced in AD and cardiovascular risk factors such as high blood pressure are correlated with increased risk for developing AD, but the mechanism was not known. Curiously, the blood flow decrease occurs very early, even before cognitive signs.
This international, interdisciplinary team has uncovered a potential cause for decreased blood flow in AD and is working on strategies to mitigate the blood flow deficit. At Cornell, the Schaffer-Nishimura labs found that capillaries in the brains of mouse models of AD are occasionally plugged by white blood cells. Although it is only a very small fraction of blood vessels, Lorthois is investigating how this small number of plugged vessels can actually lead to a surprisingly large blood flow deficit in the brain tissue. Lorthois is a leading expert on fluid dynamics and models how blood cells move through the vasculature. The motion of blood cells in blood vessels is a vexingly difficult system because the cells take up about half of the volume of blood, so that commonly used models of fluid mechanics cannot explain how blood moves in the living organisms. Her findings may explain the blood flow decrease in Alzheimer patient brains. The imaging method used on mice cannot be used on humans, so although human image studies also find that there is a blood flow deficit in AD patients, there is no way to directly evaluate what is happening at the capillary level. Computational models of blood flow can be used to extrapolate the mouse results to humans. A neurologist who has long studied the effects of inflammation and blood flow regulation in the brain, Iadecola contributes clinical and molecular insight on the causes of these capillary plugs. Inflammation is a major aspect of Alzheimer’s disease and collaboration has revealed several potential mechanisms that lead to the vascular insufficiency. Excitingly, because there is a link between blood flow decrease and the speed of AD progress, this collaboration may lead to a novel therapeutic target that could delay the onset of this devastating disease.