BE Seminar: “Systems-level Analyses of the Human Gut Microbiome” (Ilana Lauren Brito)

Ilana Lauren Brito, Ph.D.

Speaker: Ilana Lauren Brito, Ph.D.
Assistant Professor, Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering
Meinig School of Biomedical Engineering
Cornell University

Date: Thursday, October 28, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216

Abstract: A major question regarding the human gut microbiota is: by what mechanisms do our most intimately associated organisms affect human health? In this talk, I will present several systems-level approaches that we have developed to address this fundamental question. My lab has pioneered methods that leverage protein-protein interactions to implicate bacterial proteins in human pathways linked to disease, revealing for the first time a network of interactions that affect diseases such as colorectal cancer, inflammatory bowel disease, type 2 diabetes and obesity that can be mined for novel therapeutics and therapeutic targets. I will present novel methods that that enable deeper insight into the transcriptome of organisms within our guts and their spatial localization. Finally, I will shift to the problem of the spread of antibiotic resistance, in which the gut microbiota are implicated. Pathogens become multi-drug resistance by acquiring resistance traits carried by the gut microbiota. Studying this process in microbiomes is inherently difficult using current methods. I will present several methods that enable tracking of genes within the microbiome and computational tools that predict the network of gene transfer between bacteria. Overall, these systems-level tools provide deep insight into the knobs we can turn to engineer outcomes within the microbiome that can improve human health.

Ilana Brito Bio: Ilana Brito is an Assistant Professor of Biomedical Engineering at Cornell University. Ilana received a BA from Harvard and a PhD from MIT. She started her postdoc as an Earth Institute Postdoctoral Fellow at Columbia University where she launched the Fiji Community Microbiome Project, a study aimed at tracking microbiota across people and their social networks, and continued this work at MIT and the Broad Institute working with Eric Alm. In her lab at Cornell, Ilana and her team are developing a suite of experimental systems biology tools to probe the functions of the human microbiome in a robust, high-throughput manner. Ilana has received numerous accolades for her work, including a Sloan Research Fellowship, Packard Fellowship, a Pew Biomedical Research Scholarship and an NIH New Innovator Award.

Bioengineering News Round-Up (April 2020)

by Sophie Burkholder

How to Heal Chronic Wounds with “Smart” Bandages

Some medical conditions, like diabetes or limb amputation, have the potential to result in wounds that never heal, affecting patients for the rest of their lives. Though normal wound-healing processes are relatively understood by medical professionals, the complications that can lead to chronic non-healing wounds are often varied and complex, creating a gap in successful treatments. But biomedical engineering faculty from the University of Connecticut want to change that.

Ali Tamayol, Ph.D., an Associate Professor in UConn’s Biomedical Engineering Department, developed what he’s calling a “smart” bandage in collaboration with researchers from the University of Nebraska-Lincoln and Harvard Medical School. The bandage, paired with a smartphone platform, has the ability to deliver medications to the wound via wirelessly controlled mini needles. The minimally invasive device thus allows doctors to control medication dosages for wounds without the patient even having to come in for an appointment. Early tests of the device on mice showed success in wound-healing processes, and Tamayol hopes that soon, the technology will be able to do the same for humans.

A New Patch Could Fix Broken Hearts

Heart disease is by far one of the most common medical conditions in the world, and has a high risk of morbidity. While some efforts in tissue engineering have sought to resolve cardiac tissue damage, they often require the use of existing heart cells, which can introduce a variety of complications to its integration into the human body. So, a group of bioengineers at Trinity College in Dublin sought to eliminate the need for cells by creating a patch that mimics both the mechanical and electrical properties of cardiac tissue.

Using thermoelastic polymers, the engineers, led by Ussher Assistant Professor in Biomedical Engineering Michael Monaghan, Ph.D., created a patch that could withstand multiple rounds of stretching and exhibited elasticity: two of the biggest challenges in designing synthetic cardiac tissues. With the desired mechanical properties working, the team then coated the patches with an electroconductive polymer that would allow for the necessary electrical signaling of cardiac tissue without decreasing cell compatibility in the patch. So far, the patch has demonstrated success in both mechanical and electrical behaviors in ex vivo models, suggesting promise that it might be able to work in the human body, too.

3-D Printing a New Tissue Engineering Scaffold

While successful tissue engineering innovations often hold tremendous promise for advances in personalized medicine and regeneration, creating the right scaffold for cells to grow on either before or after implantation into the body can be tricky. One common approach is to use 3-D printers to extrude scaffolds into customizable shapes. But the problem is that not all scaffold materials that are best for the body will hold up their structure in the 3-D printing process.

A team of biomedical engineers at Rutgers University led by Chair of Biomedical Engineering David I. Schreiber, Ph.D., hopes to apply the use of hyaluronic acid — a common natural molecule throughout the human body — in conjunction with polyethylene glycol to create a gel-like scaffold. The hope is that the polyethylene glycol will improve the scaffold’s durability, as using hyaluronic acid alone creates a substance that is often too weak for tissue engineering use. Envisioning this gel-like scaffold as a sort of ink cartridge, the engineers hope that they can create a platform that’s customizable for a variety of different cells that require different mechanical properties to survive. Notably, this new approach can specifically control both the stiffness and the ligands of the scaffold, tailoring it to a number of tissue engineering applications.

A New Portable Chip Can Track Wide Ranges of Brain Activity

Understanding the workings of the human brain is no small feat, and neuroscience still has a long way to go. While recent technology in brain probes and imaging allows for better understanding of the organ than ever before, that technology often requires immense amounts of wires and stationary attachments, limiting the scope of brain activity that can be studied. The answer to this problem? Figure out a way to implant a portable probe into the brain to monitor its everyday signaling pathways.

That’s exactly what researchers from the University of Arizona, George Washington University, and Northwestern University set out to do. Together, they created a small, wireless, and battery-free device that can monitor brain activity by using light. The light-sensing works by first tinting some neurons with a dye that can change its brightness according to neuronal activity levels. Instead of using a battery, the device relies on energy from oscillating magnetic fields that it can pick up with a miniature antenna. Led in part by the University of Arizona’s Gutruf Lab, the new device holds promise for better understanding how complex brain conditions like Alzheimer’s and Parkinson’s might work, as well as what the mechanisms of some mental health conditions look like, too.

People & Places

Each year, the National Academy of Engineering (NAE) elects new members in what is considered one of the highest professional honors in engineering. This year, NAE elected 87 new members and 18 international members, including a former Penn faculty member and alumna Susan S. Margulies, Ph.D. Now a professor of Biomedical Engineering at Georgia Tech and Emory University, Margulies was recognized by the NAE for her contributions to “elaborating the traumatic injury thresholds of brain and lung in terms of structure-function mechanisms.” Congratulations, Dr. Margulies!

Nimmi Ramanujam, Ph.D., a Distinguished Professor of Bioengineering at Duke University, was recently announced as having one of the highest-scoring proposals for the MacArthur Foundation’s 100&Change competition for her proposal “Women-Inspired Strategies for Health (WISH): A Revolution Against Cervical Cancer.” Dr. Ramanujam’s proposal, which will enter the next round of competition for the grant, focuses on closing the cervical cancer inequity gap by creating a new model of women-centered healthcare.

Bioengineering Round-Up (October 2019)

by Sophie Burkholder

Innovations in Advancing a Cure for Diabetes

The blue circle is the global symbol for diabetes. Wikimedia Commons.

Diabetes is one of the more common diseases among Americans today, with the American Diabetes Association estimating that approximately 9.5 percent of the population battles the condition today. Though symptoms and causes may vary across types and patients, diabetes generally results from the body’s inability to produce enough insulin to keep blood sugar levels in check. A new experimental treatment from the lab of Sha Jin, Ph.D., a biomedical engineering professor at Binghamton University, aims to use about $1.2 million in recent federal grants to develop a method for pancreatic islet cell transplantation, as those are the cells responsible for producing insulin.

But the catch to this new approach is that relying on healthy donors of these islet cells won’t easily meet the vast need for them in diabetic patients. Sha Jin wants to use her grants to consider the molecular mechanisms that can lead pluripotent stem cells to become islet-like organoids. Because pluripotent stem cells have the capability to evolve into nearly any kind of cell in the human body, the key to Jin’s research is learning how to control their mechanisms and signaling pathways so that they only become islet cells. Jin also wants to improve the eventual culture of these islet cells into three-dimensional scaffolds by finding ways of circulating appropriate levels of oxygen to all parts of the scaffold, particularly those at the center, which are notoriously difficult to accommodate. If successful in her tissue engineering efforts, Jin will not only be able to help diabetic patients, but also open the door to new methods of evolving pluripotent stem cells into mini-organ models for clinical testing of other diseases as well.

A Treatment to Help Others See Better

Permanently crossed eyes, a medical condition called strabismus, affects almost 18 million people in the United States, and is particularly common among children. For a person with strabismus, the eyes don’t line up to look at the same place at the same time, which can cause blurriness, double vision, and eye strain, among other symptoms. Associate professor of bioengineering at George Mason University, Qi Wei, Ph.D., hopes to use almost $2 million in recent funding from the National Institute of Health to treat and diagnose strabismus with a data-driven computer model of the condition. Currently, the most common method of treating strabismus is through surgery on one of the extraocular muscles that contribute to it, but Wei wants her model to eventually offer a noninvasive approach. Using data from patient MRIs, current surgical procedures, and the outcomes of those procedures, Wei hopes to advance and innovate knowledge on treating strabismus.

A Newly Analyzed Brain Mechanism Could be the Key to Stopping Seizures

Among neurological disorders, epilepsy is one of the most common. An umbrella term for a lot of different seizure-inducing conditions, many versions of epilepsy can be treated pharmaceutically. Some, however, are resistant to the drugs used for treatment, and require surgical intervention. Bin He, Ph. D., the Head of the Department of Biomedical Engineering at Carnegie Mellon University, recently published a paper in collaboration with researchers at Mayo Clinic that describes the way that seizures originating at a single point in the brain can be regulated by what he calls “push-pull” dynamics within the brain. This means that the propagation of a seizure through the brain relies on the impact of surrounding tissue. The “pull” he refers to is of the surrounding tissue towards the seizure onset zone, while the “push” is what propagates from the seizure onset zone. Thus, the strength of the “pull” largely dictates whether or not a seizure will spread. He and his lab looked at different speeds of brain rhythms to perform analysis of functional networks for each rhythm band. They found that this “push-pull” mechanism dictated the propagation of seizures in the brain, and suggest future pathways of treatment options for epilepsy focused on this mechanism.

Hyperspectral Imaging Might Provide New Ways of Finding Cancer

A new method of imaging called hyperspectral imaging could help improve the prediction of cancerous cells in tissue specimens. A recent study from a University of Texas Dallas team of researchers led by professor of bioengineering Baowei Fei, Ph.D., found that a combination of hyperspectral imaging and artificial intelligence led to an 80% to 90% level of accuracy in identifying the presence of cancer cells in a sample of 293 tissue specimens from 102 patients. With a $1.6 million grant from the Cancer Prevention and Research Institute of Texas, Fei wants to develop a smart surgical microscope that will help surgeons better detect cancer during surgery.

Fei’s use of hyperspectral imaging allows him to see the unique cellular reflections and absorptions of light across the electromagnetic spectrum, giving each cell its own specific marker and mode of identification. When paired with artificial intelligence algorithms, the microscope Fei has in mind can be trained to specifically recognize cancerous cells based on their hyperspectral imaging patterns. If successful, Fei’s innovations will speed the process of diagnosis, and potentially improve cancer treatments.

People and Places

A group of Penn engineering seniors won the Pioneer Award at the Rothberg Catalyzer Makerthon led be Penn Health-Tech that took place from October 19-20, 2019. SchistoSpot is a senior design project created by students Vishal Tien (BE ‘20), Justin Swirbul (CIS ‘20), Alec Bayliff (BE ‘20), and Bram Bruno (CIS ‘20) in which the group will design a low-cost microscopy dianostic tool that uses computer vision capabilities to automate the diagnosis of schistosomiasis, which is a common parasitic disease. Read about all the winners here.

Virginia Tech University will launch a new Cancer Research Initiative with the hope of creating an intellectual community across engineers, veterinarians, biomedical researchers, and other relevant scientists. The initiative will focus not only on building better connections throughout departments at the university, but also in working with local hospitals like the Carilion Clinic and the Children’s National Hospital in Washington, D.C. Through these new connections, people from all different areas of science and engineering and come together to share ideas.

Associate Professor of Penn Bioengineering Dani Bassett, Ph.D., recently sat down with the Penn Integrates Knowledge University Professor Duncan Watts, Ph.D., for an interview published in Penn Engineering. Bassett discusses the origins of network science, her research in small-world brain networks, academic teamwork, and the pedagogy of science and engineering. You can read the full interview here.

An all-female group of researchers from Northern Illinois University developed a device for use by occupational therapists that can capture three-dimensional images of a patient’s hand, helping to more accurately measure the hand or wrist’s range of motion. The group presented the abstract for their design at this year’s meeting of the Biomedical Engineering Society here in Philadelphia, where Penn students and researchers presented as well.

Week in BioE (October 6, 2017)

We Bleed Green

field goalBiomechanics is a subdiscipline within bioengineering with many applications that include studying how tissue forms and grows during development (see our profile of incoming faculty member Alex Hughes to learn more) and determining how the ‘imprint’ of spine-based pain can be treated with anti-inflammatory medication (see story here on work from the lab of Dr. Beth Winkelstein). Understanding and analyzing human performance are other areas of biomechanics application. On September 24, Eagles kicker Jake Elliott set a team record when he kicked a 61 yard field goal at the end of regulation time to beat the Giants. Marking the achievement, the Philadelphia Inquirer featured an interview with Dr. Chase Pfeifer, a biomedical engineer from the University of Nebraska-Lincoln (UNL), to find out what factors contribute to a successful field goal from this distance. Pfeifer has both knowledge and experience with this question; he was a backup kicker for the Florida State Seminoles as an undergraduate. In the Inquirer, Dr. Pfeifer explained to readers the biophysics behind Elliott’s record kick.

Dr. Pfeifer assures readers that there’s more to kicking a 61-yard field goal than strong muscles. He explains, “The timing of muscle activation was actually more important than muscle strength in achieving that higher foot velocity.” Four muscle groups were activated by Elliott to set his record. In addition, Pfeifer’s colleague at UNL, Professor Tim Gay of the physics department, explained to the Inquirer how the climatic conditions favored Elliott’s success. Specifically, since it was a hot day, the air was less dense, allowing for longer kick distances.

Speaking of football, a new article in Annals of Biomedical Engineering offers some hope for NFL players and the league itself in the wake of growing awareness and concern about chronic traumatic encephalopathy (CTE). The increased focus on CTE has resulted in increased research on the condition and its prevention. Real-time measurement of impact energy in head injuries has, until now, relied on measurements of the motion of the head or helmet, rather than measuring the impact energy directly.

In the Annals article, scientists from Brigham Young University, including David T. Fullwood, Ph.D., professor of mechanical engineering, report on the testing of a new sensor used to measure the impact event. The authors implanted nano-composite foam (NCF) sensors into football helmets and then submitted the helmets to two dozen drop tests. The data collected from the foam sensors were compared to two of the most widely used indices to measure head injury risk, achieving excellent correlation (>90%) with injury risk indicators. The authors intend to test newer models of the sensors in the future, as well as in vivo testing.

Breast Cancer News

Despite significant advances in diagnosis and treatment, breast cancer remains the most common cancer in women. More than 300,000 women are newly diagnosed in the United States each year. Maximizing the effectiveness of treatment involves early detection of the tumor and its metastasis. Imaging plays a key role in this process. However, early tumors are very small, making their detection quite difficult.

In response to this challenge, Zheng-Rong Lu, Ph.D., the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve University, has coauthored a paper recently published in Nature Communications showing that a newly developed type of molecule could be used for highly sensitive magnetic resonance imaging (MRI) to detect and stratify early breast tumors.

Dr. Lu and his colleagues engineered molecules called fullerenes, which are hollow, spherical molecules of carbon. The team embedded gadolinium, a rare earth metal that is easily detected with MR imaging, into the fullerene to create metallofullerenes. They tested these metallofullerenes both in vitro and in a mouse model to determine how well they enhanced the ability of MRI to detect tumors. Metallofullerene particles could not only distinguish cancers more effectively on MRI, but they could also distinguish more aggressive tumor types from less aggressive ones. In addition, they found that metallofullerenes rapidly cleared from the body via the kidneys, ensuring that these agents would pose minimal toxicity risk. If this technology proves effective in humans, it could significantly improve the early detection of breast cancer and, in turn, survival rates.

One possible risk for breast cancer patients is the metastasis of the cancer to other body regions.  Scientists at Cornell identified a mineral process underlying breast cancer metastasis to bones, reporting their findings in PNAS. Led by Claudia Fischbach-Teschl, Ph.D., associate professor of biomedical engineering at Cornell, the authors investigated how hydroxylapatite — a naturally occurring mineral — participates in metastasis.

Dr. Fischbach-Teschl and her colleagues used X-ray scattering and Raman spectroscopy to examine the nanostructures of hydroxylapatite in the bones of mice with and without breast cancer. They found that bones were more likely to be metastasized by primary breast tumors if the hydroxylapatite crystals in them were less mature. Before the cancer spreads to the bone, the authors found that the cancer “communicates” with these immature crystals, preparing sites in the bone to which the cancer can spread.

With 80% of metastatic breast cancer cases spreading to the bones, the discovery of the Cornell team could contribute enormously to preventing metastasis — not only of breast cancer but also of any cancer with a greater likelihood of spreading to the bones.

A Review of Glucose Monitoring Technology

Our ability to treat diabetes has consistently improved over the years, but the need for patients with the disease to monitor their blood glucose requires either multiple needle pricks or invasive insulin pumps.  However, several technologies are in development around the world to make blood glucose monitoring less cumbersome. In a new article published in Bioengineering, engineers in the United Arab Emirates offer a review of the latest technologies, including analytic methods that could streamline decisions on doses of insulin to offset high glucose levels.

People and Places

The University of California, Davis, opened its Molecular Prototyping and BioInnovation Laboratory (MPBIL) in 2014. Since then, the “biomaker lab” has stood as an example of the future of biotechnology education. In collaboration with UCD’s First-Year Seminar Program, the MPBIL has launched a student-designed pilot course that has thus far yielded three seminars. You can read more about UCD’s innovative program at their Web site.

To promote diversity in engineering, the cosmetics company L’Oréal started the L’Oréal USA For Women in Science Program, which awards Changing the Face of STEM mentoring grants. Among this year’s recipients is John Hopkins University’s Sridevi Sarma, Ph.D. Dr. Sarma, who is an associate professor of biomedical engineering, will use her grant in collaboration with the Girls Scouts of Central Maryland to promote physics education for young women. Congratulations to her!

Pressure Sores Targeted by Flysole

Among the myriad medical complications caused by diabetes, pressure sores of the feet are among the most troubling. Because of the common  complication of peripheral neuropathy, people with diabetes are often unable to determine how much pressure is being exerted on their feet. As a result, they cause foot ulcers, which can become infected, leading in the worst cases to amputation.

pressure sores
The Flysole combines an insole with five sensors (top) and an ankle band (bottom) to house the electrical components, including the circuit for the pressure sensors as well as the microcontroller and SD card to log the pressure data.

One of the senior design teams from the Department of Bioengineering at the University of Pennsylvania developed a project to address this problem. Their solution was Flysole (right), a prognostic implant that diabetic patients can wear to collect data on foot pressure so that the doctor can prescribe an optimal orthotic to prevent sores from developing. The team was named one of the three winners of this year’s competition.

The team, which consisted of Parag Bapna, Karthik Ramesh, Jane Shmushkis, and Amey Vrudhula, designed the Flysole as a lightweight insole with ankle band paired with software that generates a profile of the pressure on the sole of the patient’s foot. The insole has five sensors to collect these data. The cost is approximately $75 per pair.

In addition, the team made the Flysole to be reusable by including a polyurethane laminate sleeve for the individual patient. Future improvements envisioned by the students include improving the software to include recommendations for orthotics and alternate arrangements for the sole sensors.