BIOâ€‰TRANS 2018, Vol. 3
“The BIOTRANS rotations give the students time to reflect on the goals for their career and a chance to say, ‘wow, I really love this type of research,’ or perhaps even more importantly, ‘wow, I really hate this aspect of the research,’ which is really good to know.” Rafael Davalos (p. 8)
Areas of BIOTRANS research of dynamic transport processes in multiscale biological systems
4 Fluid flow in ovarian cancer 6 Irreversible electroporation 7 BIOTRANS rotations 16 Student Awards 17 BIOTRANS faculty 18 Leading the green charge 20 Faculty Spotlight 22 Alumni Corner
A community of biologists and engineers who work together to study transport in environmental and physiological systems. Editor Kristin Rose Art Director Shelley Cline Photography Daniela Cimini, Rafael Davalos, Iuliana Lazar, David Schmale, Jake Socha, Kristin Rose Cover image: Members of the Schmale Lab are using teams of unmanned systems to study flows in the environment. Here, a fluorescent dye is released into the water. An unmanned surface vehicle (USV) moves into position, and deploys an ROV to track the dye underwater. A drone images the plume, and collects samples of the dye with a 3d-printed device to return to land for analysis.
Message from the director
Welcome to Biological Transport (BIOTRANS) Magazine, our third annual issue highlighting our interdisciplinary graduate education program at Virginia Tech. We are a community of biologists and engineers that collaborate to study transport in environmental and physiological systems. Our students and faculty have been hard at work during the past year!
We welcomed three new graduate students to the BIOTRANS family: Erica Pack, Xiaochu Li, and Hyunggon Park. Erica is a graduate of Pennsylvania State University with a B.S. in forensic science. She’ll be studying the effects of mycotoxin consumption in swine with co-advisors Drs. David Schmale and Raffaella De Vita. Xiaochu earned bachelor and masters degrees in electrical engineering at Hebei University of Engingeering and Beihang University in China. His research will focus in two areas: pattern formation in a bacteriaphage system and control of chromosome dynamics in eukaryotic cells with co-advisors Drs. Jing Chen and Daniela Cimini. Hyunggon joins us after earning bachelor and masters degrees in mechanical engineering at Sungkyunkwan University in Korea and the University of Southern California. He’ll be working on spore dispersal in nature by rain and jumping-drop condensation with Drs. Jonathan Boreyko and David Schmale. We also welcomed 3 new faculty to the BIOTRANS family, Drs. Boreyko, Lahondère, and Vinauger. Check out their research on the web pages below. Dr. Jonathan Boreyko, Assistant Professor, Department of Biomedical Engineering and Mechanics https://www.beam.vt.edu/boreyko/ Dr. Chloé Lahondère, Research Assistant Professor, Department of Biomechemistry https://www.chloelahondere.com Dr. Clément Vinauger, Assistant Professor, Department of Biomechemistry https://www.vinaugerlab.com/ Our faculty have received many sponsored research awards, including: Drs. David Schmale, Sunny Jung, and Jonathan Boreyko were awarded a USDA grant for ~$500K to understand how rain splash and condensation due to the jumping-droplet effect influence dispersal of wheat pathogens. Drs. Raffaella De Vita and Schmale are part of a team that received a $200K grant from the Pratt Foundation to study mycotoxin-contaminated ethanol co-products related to swine feed. Drs. Daniela Cimini and Eva Schmelz are studying extra chromosomes as drivers of tumor formation and adaptation to perturbations in the microenvironment as part of an ICTAS grant of $15K. You can read about the awards our students have received on p. 16. As you can see, there are so many exciting things going on with BIOTRANS, with more to follow in the coming year. Enjoy the third issue of our magazine!
Jake Socha, Ph.D. Director of BIOTRANS
Virginia Tech researchers examine role of fluid flow in ovarian cancer progression by Emily Roediger
New research from Virginia Tech is moving physicians closer to pinpointing a predictor of ovarian cancer, which could lead to earlier diagnosis of what is known as the “silent killer.” Ovarian cancer spreads throughout the body undetected and so has almost always progressed to an advanced stage before patients receive a diagnosis. Symptoms are often vague, and doctors currently have no reliable diagnostic test for ovarian cancer at their disposal. If scientists could identify what triggers healthy ovarian cells to turn malignant, they’d at least be able to pinpoint a predictor of the disease. Such a predictor might lead to an earlier diagnosis, which could lead to more effective treatment and save the lives of thousands of women each year. Published in PLoS ONE, a Virginia Tech study found that cancerous cells in the abdominal cavity exposed to fluid shear
stress – the force effect of the body’s fluid moving along and around organs – caused those cells to become more aggressive. Additionally, the researchers discovered that benign cells exposed to fluid shear stress began to look more and more like cancer. “We saw those aggressive cancer cells continue to get more aggressive,” said Alexandra Hyler, a BIOTRANS doctoral student in the Department of Biomedical Engineering and Mechanics in the College of Engineering and the study’s lead author. “When we put those cells under conditions that mimicked your basic, everyday fluid flow in a healthy individual, they showed traits indicative of progression, like changes in their cytoskeleton and increased focal adhesions. These cells also started forming tumor-like structures, or what we call spheroids.” “In the benign cells, it got even scarier,” said Hyler. “Those cells started to look like aggressive cells. We were actually seeing traits of cancerous cells exhibited in these benign cells.”
Hyler, who first became interested in the project from a women’s health perspective when she joined the BIOTRANS program several years ago, explained that the physical environment of cancer has recently emerged as a hallmark of the disease. As such, environments like the abdominal cavity, known as the peritoneal cavity, have become a target for many cancer researchers. The peritoneal cavity is the largest fluidfilled space in the body and extends from the base of the diaphragm down to a woman’s ovaries. Fluids in the peritoneal cavity are constantly moving against organs. Even when the body is sleeping, that fluid keeps swirling as it responds to the motion of the muscles and systems it surrounds – the digestive tract processing food or the diaphragm contracting with every breath, for example. Fluid volume in the peritoneal cavity is typically small, but levels can increase drastically in women with ovarian cancer. “Where the ovaries are located at the base of that cavity is very susceptible to fluid movement,” said Hyler. “Those
“If we discover how these cells respond to the physical stress of fluid shear, we might be able to specifically inhibit these signaling pathways and delay, or even prevent, the survival of metastases and their secondary outgrowth.” Alexandra Hyler
cells can easily get picked up from the base of your abdomen and taken to other locations.” To study how fluid shear stress affected the development and progression of ovarian cancer, the researchers subjected mouse ovarian cells at three different stages – benign, slowly developing cancerous, and aggressively cancerous – to a system of fluid flow similar to what actually happens in the body. They paralleled this dynamically progressive mouse model to ovarian cells from human patients at the benign and cancerous stages. “We used these mouse cells to validate our findings and to show that the results were similar to what we were seeing of ovarian cancer in the human cells,” said Hyler. “The mouse cells helped us validate the overall relevancy of the model.” Eventually, the researchers hope to answer questions like how and when the cells transition from benign to cancerous. Future studies could address protein and gene activation as well as a further examination of the role fluid shear stress
plays in the promotion of cancer invasion.
earlier diagnosis and treatment.”
“If we discover how these cells respond to the physical stress of fluid shear, we might be able to specifically inhibit these signaling pathways and delay, or even prevent, the survival of metastases and their secondary outgrowth,” said corresponding author Eva Schmelz, an associate professor in the Department of Human Nutrition, Foods, and Exercise. “These events could be targets for specific drugs that could prolong the life of women with metastatic ovarian cancer.”
“We’re trying to create a better understanding of this disease,” she said.
Hyler is already working on a better system for controlling shear stress in future experiments, which could be used for long-duration studies that might be able to correlate fluid shear stress magnitudes to cellular responses. “There has to be an underlying biological mechanism at work here, and we don’t have the answer to that question yet,” said Hyler. “If you could pinpoint something that’s responding to the changes of that mechanical force, or what we call mechanosensors, then you’re talking about ways to step in for
This research was funded in part by the National Science Foundation and the Virginia Tech Institute for Critical Technology and Applied Science. Additional authors include Mark Stremler and Rafael Davalos, of the Department of Biomedical Engineering and Mechanics; Megan Brown, of the Department of Human Nutrition, Foods and Exercise; and Nicolaas Baudoin and Daniela Cimini of the Department of Biological Sciences and the Biocomplexity Institute.
Image, above center: Alexandra Hyler prepares samples for testing in the lab. Hyler led a study that examined the effects of fluid shear stress on ovarian cancer development and progression, which found that even normal fluid flow in the abdominal cavity can cause cancerous and benign cells to become more aggressive. Image, above right: After multiple rounds of fluid shear stress exposure, human cells in the study began to form tumor-like structures known as spheroids (pictured). Spheroids are indicative of aggressive disease traits.
Virginia Tech researchers treat brain cancer with electrotherapy By Jenny Kincaid Boone, Rich Ulsh, and Kristin Rose
Virginia Tech researchers are enabling doctors to treat brain tumors once considered inoperable using irreversible electroporation, also known as electric field ablation. The technique was developed by Rafael Davalos, the L. Preston Wade Professor of Biomedical Engineering and Mechanics in the College of Enginnering, and his team. Irreversible electroporation opens a cancer cell’s pores using low-level electrical pulses, which allows for medicine to be better received by the cell. This new process is also suited to destroy brain tumors and can potentially prevent patients from suffering through radiation treatment. Irreversible electroporation has been successful in treating more than 6,000 patients suffering from liver, kidney, pancreatic, and prostate cancer. Davalos and John Rossmeisl, professor of neurology and neurosurgery at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech, were recently part of a team awarded a $9.2 million grant from the National Institutes of Health’s National Cancer Institute that includes other engineers, cancer researchers, surgeons, and veterinarians from Virginia Tech and Wake Forest University to develop treatments for brain cancer. The Virginia-Maryland College of Veterinary Medicine at Virginia Tech’s clinical research program involves both primary research focused on advancing the treatment and diagnosis of diseases through animal clinical trials and comparative research in which spontaneous diseases in animals can be used as models of human disease. The five-year grant will fund four different approaches to treating brain cancer, specifically glioblastoma, the most Image, right: Professor Rafael Davalos. Image, far right top, microfluidic devices. Image, far right bottom: Philip Graybill.
common and deadliest form of brain cancer in adults. The median survival rate is about fourteen months. Davalos, a faculty member of BIOTRANS, leads one of the four projects, focusing on irreversible electroporation. In Davalos’ lab, BIOTRANS graduate student Philip Graybill is conducting some of this research. He is using these high intensity electric fields to target cancers and his research mainly focuses on the blood-brain barrier, brain tumors, and glioblastomas in particular. Graybill says, “these high intensity fields can open the blood-brain barrier so that chemotherapy can be delivered to the primary tumor and area around the tumor. This technique can be used in conjunction with surgery, where an electrical probe is inserted into the primary tumor and destroys the bulk of the tumor, which can then be removed. The chemotherapy then targets and destroys the remaining cancer cells.” The grant will make it possible to begin clinical trials in humans in the next three years, said Davalos. He hopes the results of this work will increase the median survival rate of glioblastoma patients, and ultimately improve their quality of life. “You want to try to make an impact,” he said.
“This technique can be used in conjunction with surgery, where an electrical probe is inserted into the primary tumor and destroys the bulk of the tumor, which can then be removed. The chemotherapy then targets and destroys the remaining cancer cells.” Philip Graybill
feature Imagine this: You begin your Ph.D. program. As the first semester starts, you learn about the research of your home lab and new scientific techniques and technologies. Through the process, you find the research different from what you imagined and the research area begins to seem too narrow. Your personality doesn’t quite gel with the other lab members. You fear the next four to five years might be more arduous than you anticipated. You wonder: am I a good fit? In the BIOTRANS program at Virginia Tech, each graduate student’s educational plan is customized by background, expertise, and interest. The program itself offers students education and research at the biology-engineering interface that investigates dynamic transport processes in multiscale biological systems. As a general framework, each BIOTRANS graduate student will participate in one of the following tracks: Biological Sciences Track (BST) or Engineering Sciences Track (EST). These tracks are intended to aid each graduate student in developing a core expertise in either biology or engineering while pursuing a Ph.D. in a corresponding home department, and in developing proficiency in the fundamentals of the other discipline. During the first semester and a half, each BIOTRANS graduate student will participate in lab rotations through three of the BIOTRANS research groups to ensure they are a good fit for their research area—and their advisors. There are eighteen BIOTRANS faculty members, located in ten different
departments and programs across three different colleges, but not all faculty members will have rotation spots available each year. Before the fall term begins, incoming students learn more about the biology and engineering research areas before choosing three labs to rotate in. During each rotation, which lasts about seven weeks, students work on a project led by the lab’s faculty member. The goal of these projects is to expose students to the lab’s members, including students and faculty, how it’s run, its research projects, and the technical aspects of conducting the research itself. The benefit for the students is the ability to learn more about each research project and faculty member before committing to multiple years in a lab and on a project. Jake Socha, an associate professor of biomedical engineering and mechanics in the College of Engineering and the director of the BIOTRANS program, has hosted seven rotation students since the program began. “BIOTRANS is a fairly unique graduate program in that we have this truly cross-disciplinary requirement where you have people who are inclined in life sciences studying engineering and you have engineers and physical scientists going over to life sciences. They’re being immersed in those labs and those cultures. Most engineering departments and programs don’t have a rotation process,” said Socha. Socha is an organismal biomechanist studying the relationship between form and function in animals, with a broad
BIOTRANS ROTATIONS: finding a good fit, new perspective, and collaboration By Cassandra Hockman and Kristin Rose
“The rotations help students gain research experience in areas outside their comfort zone and ask them to think in different ways about interdisciplinary research.” Daniela Cimini
range of projects involving locomotion, breathing, and feeding. “My lab is intrinsically interdisciplinary; we are a biology and engineering lab that studies how animals move.” Current work in his lab focuses on gliding flight in snakes, mechanics of convection in compressible tracheal structures in insects, and dynamics of pumping in liquid feeders such as butterflies and mosquitoes. Rafael Davalos, a professor in the department of biomedical engineering and mechanics in the College of Engineering, has hosted 11 rotation students since the BIOTRANS program began. In Davalos’ lab, they research bioelectromechanical systems, a cross-disciplinary field that combines engineering and science from the nano to macro level. Using electrical feedback to perform complex procedures in biotechnology with precision and control, they have established robust methods for single cell analysis, selective cell concentration, and cancer therapy. The Davalos lab is looking at new ways to treat cancer with a process called irreversible electroporation; much of that research involves heat transfer and fluid mechanics, which is how they are related
to the BIOTRANS mission. “A lot of graduate schools across the country want their students to decide which lab to work in after just visiting for a weekend, which is a lot to ask,” said Davalos who believes that rotations are productive for students. “The BIOTRANS rotations give the students time to reflect on the goals for their career and a chance to say, ‘wow, I really love this type of research,’ or perhaps even more importantly, ‘wow, I really hate this aspect of the research,’ which is really good to know.” In the past, Davalos said the BIOTRANS program has had students who thought they wanted to concentrate on a certain area of research but after the rotations found they were even more passionate about another research area. “I always tell my students, ‘you are going to be the best in the world on this topic, so you ought to like it.’ ” Daniela Cimini, a professor of biological sciences in the College of Science and the rotation coordinator for the BIOTRANS program, has hosted 9 rotation students since the program began. She thinks the rotations are extremely beneficial for the graduate students and enhance
Images, previous page, top: Former graduate student Isaac Yeaton at his thesis defense. Image courtesy of Jake Socha. Imaging of cells from the Cimini lab. Images courtesy of Daniela Cimini. Image, right: Electroporation cancer research in the Davalos lab. (a) Liver tissue is sectioned into cylindrical samples (a) and placed into acrylic molds (b), which are then placed between two parallel plate electrodes (c). Image courtesy of Rafael Davalos.
collaboration between faculty members. “The program attracts really curious, high-level students who are interested in interdisciplinary work,” Cimini said. “The students usually come to the program with an idea of who they would like to work with, but sometimes they change their mind based on their rotations.” Cimini says “the rotations help students gain research experience in areas outside their comfort zone and asks them to think in different ways about interdisciplinary research. I’ve had rotation students with purely computational backgrounds who come into my lab and are challenged with learning how to pipette and learning new biological techniques they’ve never seen before. It is a really enriching experience. Engineers and life scientists usually think in very different ways, and I think it is important for the graduate students to experience this early on because then they can start to ask questions from different points of view. The rotations give them new perspectives.” The research in Cimini’s lab focuses on two major areas: the role of mechanics and dynamics of mitotic apparatus components in ensuring accurate chromosome segregation during cell division, and the causes and consequences of aneuploidy (abnormal chromosome numbers) in normal and cancer cells. Over the years, Iuliana Lazar, an associate professor of biological sciences in the College of Science, has hosted six rotation students in her lab from the BIOTRANS program. Lazar’s research is focused on elucidating the molecular mechanisms
feature of breast cancer cell cycle via proteomics and systems biology approaches. Her lab uses and develops advanced mass spectrometry and micro/nano-fluidic technologies that enable a detailed interrogation of biological systems. Lazar found the rotations in her lab to be helpful “for the students who were interested in learning about how high-throughput technologies such as mass spectrometry and proteomics are integrated into studies focused on addressing human disease.” Lazar’s lab is also developing microfluidic devices that enable an advanced characterization of biological samples. “The lab-on-a-chip technology is directed toward creating miniaturized platforms for complex sample analysis as a front end to mass spectrometry detection,” Lazar said. “Functional elements for fluidic propulsion, valving, mixing, enzymatic reactions and sample separations are being developed. Most importantly, my lab is interested in developing the interface between microfluidics and mass spectrometry, to create a fully integrated, hand-held, stand-alone platform that facilitates the detection process.” Jing Chen, an assistant professor of biological sciences in the College of Science, hosted two BIOTRANS rotation students this past year, and one joined her lab. In the Chen lab, they build mathematical models to study how biological systems function. They typically work in close collaboration with experimental groups, and the current research projects in the lab include: circadian gene expression, cell division mechanisms, bacterial motility, and phage-bacteria interactions. “Although some students already have a Ph.D. advisor settled when they enter the program, I think the rotation experience broadens the horizon for them and constitutes a valuable part of their training,” said Chen. “This is because as researchers, we face everchanging questions, and often times the most creative ideas originate from unconventional, interdisciplinary perspectives.”
Xiaochu Li, who has joined Chen’s lab, chose to work on mathematical modeling of chromosome segregation, a collaborative project between Chen and Cimini. Besides rotating with Chen, he rotated in the labs of Cimini and Raffaella De Vita, an associate professor of biomedical engineering and mechanics in the College of Engineering. Li researched techniques of extracting chromosomes from live cells and measuring their mechanical properties. “This wet lab experience enhanced his intuitive sense about the system he will build mathematical models for, and improved his ability to communicate with other scientists in the collaboration,” said Chen. The BIOTRANS students are also expected to give presentations about their research after each rotation. “The students are not expected to have data after each rotation, but frequently they do,” says Cimini. By the end of the third rotation, students will select advisors and co-advisors for their continued research consisting of at least one faculty participant from each of the two tracks. They submit their top choices to Cimini, who works to best place them. The BIOTRANS rotations are also helpful because sometimes the students start to collaborate. Engineering and biology graduate students, who would not normally mix in other graduate programs begin to “talk to each other and seek help from each other. Students with a biology background initiate collaborations with engineering students with a programming or mathematical modeling background. I think it is really pretty amazing,” said Cimini.
Microfluidic devices for phosphopeptide enrichment and sample separation in the Lazar lab. Photos courtesy of Iuliana Lazar.
STU DE NT a n d G RA DUATE PROFI L E S
Erica Pack second year Ph.D. student in plant pathology, physiology, and weed science Co-advisors: David Schmale and Raffaella De Vita
second year Ph.D. student in biological sciences Co-advisors: Jing Chen and Daniela Cimini
Xiaochu Li came to Virginia Tech after receiving his bachelor’s degree in automation and engineering at Hebei University and a master’s degree in control science and engineering at Beihang University in China. Xiaochu was attracted to the BIOTRANS program because it was interdisciplinary, and he was intrigued by the idea that he would be able to think, collaborate, and problem solve at the interface of biology and engineering.
What was the rotation process like? “My first rotation was in Dr. Chen’s lab, where I built the mathematical model of the bacteria phage system to study the dynamic interactions between bacteria and phages. My second rotation was in Dr. Cimini’s lab. We wanted to remove the chromosomes from cells by vortex without damaging the chromosome’s mechanical properties. This was the first time that I was exposed to bench work. My third rotation was in Dr. De Vita’s lab, where we continued my work from Dr. Cimini’s lab. We tried removing the chromosome by puncturing the cell membrane with micro-needles. During the rotation processes, everyone in the lab was really kind to me. They taught me how to conduct the experiments and how to use equipment I was unfamiliar with. This experience helped me to build the connection between biology and engineering.” How did you know which lab to choose? “I weighed this important decision by considering my research preferences, strengths, and discussions with Dr. Chen.” His current research focuses on the bacteria-phage system
that he began in his first rotation. In the future, he will work on chromosome segregation, a collaborative project between the Chen and Cimini labs.
Erica Pack graduated from Penn State with a B.S. in forensic science and has always been a proponent of interdisciplinary research. “Forensic science is inherently interdisciplinary, involving an understanding of legal practices, and in my case, biochemistry.” When Dr. Schmale, a professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences, suggested I apply to the BIOTRANS program, I was excited to see a Ph.D. program dedicated to interdisciplinary research. Even more appealing was the fact that this program would allow me to extend my pre-existing skills into the field of engineering. While I was interested in engineering, the field always seemed too foreign to just ‘dive into,’ but this program seemed to offer a smoother transition,” said Pack.
What was the rotation process like? “There are three rotations, each of which lasts six to seven weeks. They typically take place during the first and second semester. My situation was a little different because I completed my first rotation over the summer and finished my next two rotations by the end of the first semester. My first rotation was in Dr. Schmale’s lab, where I worked on developing a method for recovering mycotoxins from swine tissue. My second rotation was with Dr. Sunny Jung, an associate professor of biomedical engineering and mechanics in the College of Engineering. In Dr. Jung’s lab, I studied the suckling frequency of animals in relation to their size. In my final rotation in Dr. De Vita’s lab, I evaluated the mechanics of the uterosacral ligament in swine.” How did you know which lab to choose? “Despite rotating in two biomedical engineering and mechanics (BEAM) labs, I didn’t actually have much prior experience in engineering, so it was pretty easy for me to choose to work in Dr. Schmale’s lab in the department of plant pathology, physiology and weed science. Of course, that was not the only reason that I chose Dr. Schmale’s lab. I simply enjoyed the project and thought my prior skillset would be of use in his lab. Since I am co-advised by Dr. De Vita, I will be working on certain projects in her lab as well.” Pack is now studying how a mycotoxin, which can be found in pig
feed, affects swine reproduction on a biochemical, clinical, and biomechanical level, which was part of the research Pack began in her rotation in Schmale’s lab.
third year Ph.D. student in biomedical engineering and mechanics Co-advisors: Rafael Davalos and Mark Stremler
Philip Graybill graduated with a B.S. in mechanical engineering and a minor in physics from Grove City College. He became interested in the interdisciplinary aspects of biology and engineering when his professor introduced him to the field of biofluid dynamics research. As an undergraduate, Graybill conducted research and modeled the shear stress of fish and squid and their undulatory locomotion. He became very interested in how engineering can answer biological questions.
What was the rotation process like? “The rotations were helpful for me. I knew I wanted to be in the field of biofluids or fluid dynamics, but I wasn’t entirely sure what that would look like for graduate research. I did three six-week rotations in the labs of Dr. Jung, Dr. Behkam, an associate professor of mechanical engineering in the College of Engineering, and Dr. Davalos. In Dr. Jung’s lab, I worked with a graduate student and studied how water droplets stick to leaves in different seasons. We were creating a model to determine how the roughness of the leaves affects this process. In Dr. Behkam’s lab, I did research to examine how bacteria adhere to certain surfaces. The long-term goal was to design improved surfaces and devices for the medical field that prevent bacterial adhesion. My third rotation was with Dr. Davalos’ lab, where I worked with his graduate student, Temple Douglas, to improve the design of a microfluidics device that uses dielectrophoresis to sort tumor subpopulations.” How did you know which lab to choose? “I really enjoyed designing microfluidic devices in my rotation in Dr. Davalos’ lab. I liked that the lab was very application focused, as Dr. Davalos says, ‘from bench to bedside.’ We are developing techniques in the lab that will have direct application in the medical field. What research is he working on now? Graybill’s current research is focused on using high intensity electrical fields to ablate tumors. He researches a technique called irreversible electroporation that can be used to open the blood-brain barrier so chemotherapy can be delivered to patients with brain tumors.
fourth year Ph.D. student in biomedical engineering and mechanics
Co-advisors: Rafael Davalos and Daniela Cimini
Temple Douglas majored in physics at Princeton University with certificates in materials science and biophysics. She has been interested since high school in quantitative and theoretical approaches to studying cancer and other health problems, with a specific focus on improving diagnostics. “I learned about the BIOTRANS program from Dr. Davalos, and was very interested in multidisciplinary research, as my own interests are quite broad,” said Douglas. She liked the idea of doing rotations to try to build a research project that would span different fields.
What was the rotation process like? “I had three eight-week rotations. I began with Dr. Cimini, where I worked on developing a mathematical model to predict aneuploid evolution. My second rotation was with Dr. Stremler, a professor in the department of biomedical engineering and mechanics in the College of Engineering, where I worked on trying to build a theoretical model for fluid shear in the peritoneal cavity. My final rotation was with Dr. Davalos where I worked on a diagnostic application that uses dielectrophoresis to sort tumor subpopulations.” How did you know which lab to choose? “It was a difficult decision, but I thought that the project with Dr. Davalos would allow me to work from both an experimental and theoretical approach interchangeably. I am in Dr. Davalos’s lab but I work frequently with others from BIOTRANS. Several BIOTRANS faculty are on my committee: Dr. Stremler, Dr. Davalos, Dr. Schmelz, and Dr. Cimini.” Douglas is currently working on the diagnostic application that uses dielectrophoresis to sort tumor subpopulations that she began in her rotation in Davalos’ lab. “The device feeds tumor subpopulations into a downstream 3D culture chamber where they can be multiplexed with different chemotherapies to determine each subpopulation’s aggressiveness, growth rate and response to treatment. In the future, this could be used to target treatments towards the most aggressive subpopulations, in an effort to prevent resistance and recurrence following chemotherapy,” said Douglas.
CURRENT STUDENT Ellen Garcia
fifth year Ph.D. student in biological sciences
Co-advisors: Daniela Cimini and Linsey Marr
Ellen Garcia graduated from Colorado Mesa University with a B.S. in Biological Sciences. She joined the BIOTRANS program with an interest in cell biology and how biology and engineering interface, but Garcia did not have a clear idea what research she wanted to focus on. She found the rotations to be helpful in determining what she found most interesting, and what she wanted to concentrate on for her dissertation project. What was the rotation process like? Ellen had three extremely successful rotations in the labs of Dr. Marr, Dr. Schmale, and Dr. Cimini for ten weeks each; she has a publication resulting from each of her rotation projects. “In Dr. Marr’s lab, in the department of civil and environmental engineering in the College of Engineering, I worked closely with her post-doc on a project to quantify the amount of virus and bacteria that is in the outdoor air. I did my second rotation with Dr. Schmale’s lab where I did an analysis on the microbes that are found in raindrops. I designed an apparatus to collect raindrops using liquid nitrogen so the raindrops would ‘superfreeze,’ and I could then perform analyses to see what bacteria and fungi were found in each individual raindrop. I have a first-author manuscript forthcoming from this research. My third rotation was with Dr. Cimini’s lab where I researched the effect on cell division by silver nanoparticles. How did you know which lab to choose? “I ultimately chose to work in Dr. Cimini’s lab because I enjoyed the focus on cell biology. The rotation project on how silver nanoparticles affect cell division that I began in her lab became my dissertation project, and I’m currently writing a manuscript describing the findings from this project. Dr. Marr co-advises me as part of the engineering track.” Ellen is continuing her dissertation research on silver nanoparticles and cell division in Cimini’s lab and then collaborating with Marr’s lab on a side project to localize virus in respiratory droplets using microscopy.
G R A D U AT E Isaac Yeaton
Ph.D. in biomedical engineering and mechanics, graduated February 2018 Co-advisors: Jake Socha and Shane Ross
Isaac Yeaton came to Virginia Tech after receiving his bachelor’s degree from the University of New Hampshire in mechanical engineering. He began his Ph.D. in a mechanical engineering lab at Virginia Tech, but heard about the BIOTRANS program through Shane Ross, a professor of biomedical engineering and mechanics in the College of Engineering, and became intrigued by the interdisciplinary nature of the program.
What was the rotation process like? “I rotated through the three labs of Dr. Schmale, Dr. Ross, and Dr. Socha. In Dr. Schmale’s lab, I studied airborne ice nucleating microbes that could change the freezing point of water. At the beginning of the program, I took Dr. Socha’s class on animal motion, and then rotated through his lab, where I studied the aerodynamics of flying snakes and 3-D camera calibration. I then rotated through Dr. Ross’ lab, where I worked on mathematical models for studying flying snakes.” How did he know which lab to choose? Yeaton was so fascinated by
the snake research from his rotations that he ended up focusing on this research for his dissertation project and working with both Dr. Socha and Dr. Ross. He ended up creating three mathematical models for studying the movements of snakes. The kinematics model calculates how the snake undulates based on the serpenoid curve, mimicking the traveling wave of muscle down the snake’s body. The dynamics model determines how the snake’s body translates and rotates during the simulated glide. Lastly, the aerodynamics model allows scientists to estimate local forces acting on the snake’s body.
Yeaton is now working at the Applied Physics Lab at Johns Hopkins University. He does research and modeling as part of the Physical
Threat Detection Group to figure out how to keep soft targets like schools and subways safe from threats like disasters and shootings. Yeaton feels that the BIOTRANS program prepared him to communicate about science effectively and helped him land his current job.
Image, left top: BIOTRANS graduate student Khaled Adjerid. Image, left bottom: Imaging of a beetle’s abdominal movement at the Advanced Photon Source in Illinois. Image, right top: BIOTRANS graduate student Talia Weiss, Image, right bottom: Isaac Yeaton at ‘the Cube,’ in the Moss Arts Center. Images courtesy of Jake Socha.
G R A D U AT E Alexandra Hyler
Ph.D. in biomedical engineering and mechanics graduated February 2018
Co-advisors: Rafael Davalos, Eva Schmelz, and Mark Stremler Alexandra Hyler came to Virginia Tech after receiving her bachelor’s degree at the University of Kansas in Chemical Engineering with honors. Hyler was attracted to BIOTRANS because “I had no idea what exact research project I wanted to tackle in graduate school. I liked working on fluid dynamics problems as they applied to medical applications, but I hadn’t settled on one exact focus. So, I really liked the idea of being able to rotate through a few labs and build a project around my interests. I didn’t even know two of the faculty members that ended up being integral advisors to my work, Drs. Schmelz and Stremler, so I was very grateful I took this route so I could really feel out the various labs, the research capabilities, and I tailored a project to my own curiosities.”
What was the rotation process like? “I’m a bit of an extreme example, but I rotated through three labs for about 2-3 months each. I ended up pulling strengths from all three of my rotations into my dissertation project. I first rotated in the lab of Dr. Schmelz in the department of human nutrition, foods, and exercise in the College of Agriculture and Life Sciences, where I focused on and learned the intricacies of ovarian cancer biology and disease progression. In Dr. Davalos’ lab, I worked on device engineering and testing platforms for precisely controlled fluids experiments. Lastly in Dr. Stremler’s lab, I delved into complex theoretical modeling to complement and develop my experimental plans and device fabrication. Tying all three areas together allowed me to comprehensively investigate ovarian cancer initiation and progression with physiologically relevant testing platforms and balancing a complete understanding of the biological complexities.” How did you know which lab to choose? “Our year of rotations, the faculty built some research projects that could tie all three rotations together. So, my project jumpstarted from this idea that all three advisors were already working on different parts of the same cancer progression problem. So, picking rotations that were in my interest area but also included faculty I didn’t know yet was a perfect way to meld all these ideas together for my project. And without trying rotations, I never would’ve met some of the faculty!” Hyler is still moving forward with her ovarian cancer research. As you can read in the news story about her PLoS ONE paper on page 4, “we found the physical environment (fluid flow) causes progression in the disease. However, we haven’t identified how this progresses the disease and why. So, I have engineered and modeled a testing platform so we can precisely control further fluid dynamics experiments on ovarian cancer cells to identify these mechanical triggers. Moving forward, we are looking at what the triggers might be and doing correlative studies of the magnitude and duration of the fluid flow exposure,” says Hyler.
Image, top: Snake gliding experiment conducted by the Socha lab. Image bottom: Research in the Socha Lab often involves trips to the Advanced Photon Source at Argonne National Laboratory to conduct x-ray imaging. Here, undergrad Jonas Scherer inserts a pressure probe into a beetle at beamline 32-ID. Images courtesy of Jake Socha. Images, opposite top: Members of David Schmale’s lab collect water samples from Claytor Lake. Image courtesy of David Schmale. Image, opposite bottom: Sharri Zamore, a postdoctoral researcher in Jake Socha’s lab at the Virginia Science Festival with a snake. Image courtesy of Jake Socha.
B I O T R A N S student awards
Melissa Kenny won the Fran Oâ€™Sullivan Women in Lenovo Leadership scholarship from the Society of Women Engineers.
Talia Weiss won the NASA-Virginia Space Grant Consortium Graduate STEM Research Fellowship to study interfacial locomotion in skittering frogs.
Khaled Adjerid was awarded the Liviu Librescu Memorial Fellowship from Virginia Tech.
won Virginia Techâ€™s Graduate Student Service Excellence Award and the Edward Carney Predictive Toxicology Award for Poster Presentation at the American Society for Cellular and Computational Toxicology Annual Meeting.
Jingren Deng won the GSDA Fellowship, Spring 2018 and Research Day Oral Presentations.
Alexandra Hyler was named the Virginia Tech Graduate Student of the Year. This award is for students across all disciplines. Wow!
B I O T R A N S faculty Jonathan Boreyko Jing Chen Daniela Cimini Rafael Davalos
Raffaella De Vita Caroline Jones Chloé Lahondère Iuliana Lazar
Linsey Marr Steve Melville Shane Ross David Schmale
Eva Schmelz Shima Shahab Jake Socha Mark Stremler
BIOTRANS faculty members are located in ten different departments and programs across three different colleges at Virginia Tech. Their research, which sits at the interface of biology and engineering, loosely falls into three categories: transport at the cellular scale, transport at the organismal scale, and transport at the environmental scale. During the application process, students must indicate three BIOTRANS faculty whose research most interests them.
Tess Thompson Clément Vinauger
Leading the green charge:
BIOTRANS Ph.D. student Ellen Garcia introduces lab sustainability program to campus By Tiffany Trent
Laboratory waste isn’t the first thing you think of when considering scientific research, yet research laboratories generate approximately 5.5 million tons of waste per year, according to a 2016 Nature article. Much of that waste — from plastic foam to packaging — could easily be recycled, reducing the waste stream from a lab and ultimately saving energy and money for research programs. Apart from waste reduction, there are many other green actions a lab can implement to foster sustainability. All that’s needed is someone to spearhead the green charge. At Virginia Tech, that someone is Ellen Garcia, a BIOTRANS Ph.D. student in Daniela Cimini’s laboratory at the Biocomplexity Institute. Cimini, a Biocomplexity Fellow, is also an Associate Professor in the Department of Biological Sciences in the College of Science and a member of the BIOTRANS faculty. In December of 2016, Garcia met the founders of My Green Lab, a nonprofit based in California working to provide sustainable solutions for research laboratories and manufacturers. Deeply
“Less than two years after Ellen's lab became the first Certified Green Lab at Virginia Tech, the university is now considering launching a campus-wide program aimed at reducing the environmental impact of labs. It's incredible - she's doing all of this while getting her Ph.D.” Allison Paradise, executive director of My Green Lab
WHEN LEFT OPEN, A SINGLE CHEMICAL FUME HOOD CAN USE AS MUCH ENERGY AS
3 . 5 H O U S E H O L D S E V E R Y D AY Image, opposite: Ph.D. student Ellen Garcia shuts the sash on a chemical fume hood. Shutting the sash when not in use is one way laboratories can be more sustainable.
Among the many resources My Green Lab offers is a green lab certification process, which is recognized as the standard for sustainable laboratory practices across North America. In one year, Garcia was able to obtain a silverlevel green lab certification, meaning that 60-69 percent of lab actions are considered sustainable.
DUE TO THE LARGE VOLUME OF AIR THAT MUST BE MOVED THROUGH THE HOOD BY THE VENTILATION SYSTEM .
inspired by My Green Lab, Garcia returned to the institute determined to implement changes. “Many sustainable practices,” Garcia notes, “are simple changes in behavior. It really just takes someone noticing and making an effort to foster change.” These changes have included reducing energy consumption by regularly turning off lights and taping over light switches powering unnecessary lighting; in-your-face reminders to turn off equipment, including vacuum lines, when not in use; and streamlining waste disposal to decrease the amount of plastic containers used. In most cases, people have to simply be encouraged and reminded to do something until it becomes a new habit. One change that has a large impact on the energy consumption of laboratories is raising the temperature of super-cooled
Illustration courtesy of www.labconco.com.
freezers from the standard -80°C to -70°C, a temperature which still preserves specimens but uses far less energy. Another change with big impact is to close the sash on chemical fume hoods. These fume hoods use as much energy in one day as three-and-a-half households. With the sash shut, energy consumption is slashed in half. Researchers can also order their supplies from companies with sustainable practices. Corning, for instance, recycles its packaging free of charge to the consumer. Garcia has managed to divert at least 30 pounds of packaging from the waste stream by working with Corning. The Biocomplexity Institute now has recycling options available to all its research labs for Corning plastic packaging, as well as pipette tip boxes from any manufacturer, thanks to a program from Fisher Scientific.
The Cimini lab is not the only one to take action. Thanks to efforts from Garcia and the research operations team, the Biocomplexity Institute has implemented a unique plastic foam recycling program. “The amount of Styrofoam we have diverted from the landfill in only a few months fills an entire stock room,” Garcia noted. Inspired by Garcia's program, other labs at Virginia Tech are working toward more sustainable lab practices throughout campus. Allison Paradise, executive director of My Green Lab said, "The impact of Ellen's work is truly inspiring. She stands out as a leader in the green labs movement, and through her actions she has demonstrated how one person can transform laboratory operations on a campus. Less than two years after Ellen's lab became the first Certified Green Lab at Virginia Tech, the university is now considering launching a campuswide program aimed at reducing the environmental impact of labs. It's incredible - she's doing all of this while getting her Ph.D. Imagine what would happen if graduate students around the country followed Ellen's lead. Life science research would be forever changed."
caserta,italy near naples
Raffaella De Vita Associate Professor Biomedical Engineering and Mechanics Department College of Engineering
What is the focus of your research? Research in my lab focuses on how biological materials behave when force is applied. We research the experimental and theoretical mechanics of nonlinear elastic, viscoelastic, and liquid crystal biological systems including pelvic floor tissues, tracheae, ligaments, tendons, cells, and lipid bilayers. A major area that we are researching right now is pelvic floor disorders. We use swine as the animal model to examine the elastic properties of the pelvic structure and then create mathematical models. There is a huge need for this research in the medical field as one in four women experience pelvic floor disorders, and there are very few people in the country researching this area.
Why did you choose to continue your career at Virginia Tech? I came to Virginia Tech right after I finished my Ph.D. at the University of Pittsburgh. My husband was hired as a professor in the mathematics department, and I was hired as a postdoctoral fellow and then a visiting assistant professor in the engineering science and mechanics department. In 2007, I applied for a tenure-track assistant professor position and was offered the job.
What do you enjoy about being an affiliated faculty member with the BIOTRANS program? I appreciate interacting with faculty and students who value interdisciplinary research. This gives me the opportunity to learn about different
fields and collaborate. I always learn things when interacting with students from very different backgrounds; I find I learn more from people who don’t work in my field than from people who do research in the same area. The different perspectives are very valuable, and everyone in the BIOTRANS program is collegial and supportive.
What advice do you have for prospective graduate students? Be open-minded and willing to accept criticism. You have to be willing to learn from and listen to people speaking in different “scientific languages” with different backgrounds. They may provide strengths and perspectives that are different than your own.
What has been your most memorable experience since joining Virginia Tech or moving to Blacksburg? One of my happiest memories is when I applied for the tenure-track, assistant professor position here and got the job. In 2012, I was given the Presidential Early Career Award for Scientists and Engineers (PECASE) and was invited to the White House to meet president Obama. I also have many happy memories of teaching and interacting with all my undergraduate and graduate students.
Image, opposite above left: Tensile test of uterosacral ligament. Electrodes apply electric stimulus to induce contractions in the tissue. Image, opposite above right: Histology of swine uterosacral ligament. Images courtesy of Raffaella De Vita.
Educational Background Ph.D. in Mechanical Engineering, University of Pittsburgh, 2005 M.S. in Mechanical Engineering, University of Pittsburgh, 2003 Laurea in Mathematics, University of Naples II, 2000
Honors and Awards Leader in Teaching, BEAM department, 2018 College of Engineering Dean’s Award for Teaching, 2017 Alumni Award for Outreach Excellence, Virginia Tech, 2017 Visiting Professorship, La Sapienza, Rome, 2016 JBME Editors’ Choice paper, 2015
“Be open-minded and willing to accept criticism. You have to be willing to
Premio Progreditur Marcianise, 2015
learn from and listen to
Paper in Highlights of Smart Materials and Structures, 2014
people speaking in different
Liviu Librescu Faculty Prize, 2014 College of Engineering Faculty Fellow, 2014-2017 College of Engineering Award for Outreach Excellence, 2014 20 under 40 ASEE Prism Magazine, 2014 PECASE Award, 2012 Excellence in Access and Inclusion Award, Virginia Tech, April 23, 2013 Scholar of the Week, Virginia Tech, August 27, 2012 NSF CAREER Award, 2012 NSF CBET Award Achievement, 2012 Paper in Highlights of Smart Materials and Structures, 2011
‘scientific languages’ with different backgrounds They may provide strengths and perspectives that are different than your own.” Raffaella De Vita
American Society of Biomechanics President’s Award, 2006
Cooking, running, biking, reading, and listening to music.
Favorite thing to do around Blacksburg
Outdoor activities, especially running and biking.
A Favorite Quote “Dream big!”
Favorite Type of Music or Artist Italian band Negramaro
Favorite Book Series
The Elena Ferrante series
Ray David, Ph.D., P.E. by Cassandra Hockman
Ray David received his Ph.D. from Virginia Tech in 2016. He was a student in the BIOTRANS program studying the dispersal of spores from a fungus, Fusarium graminearum, which wreaks havoc on many staple agricultural crops, such as corn, wheat, and barley (hint: think cereal). It can also be problematic to swine and human health if the impacted crops are ingested. The fungus spreads through air and, as Ray found, the release and spread of this fungus is affected by temperature and air humidity levels. To tackle the problem of massive crop and subsequent economic loss, Ray utilized expertise from his home field of civil and environmental engineering and from plant pathology, physiology, and weed science. Ray was co-advised by Linsey Marr, the Charles P. Lunsford Professor in civil and environmental engineering, and co-advised by David Schmale, a professor in plant pathology. Both areas, he says, gave him the ability to bring air quality research and plant biology together to effectively understand and measure fungal transport. Before coming to Virginia Tech, Ray completed a Bachelor’s and a Master’s Degree in civil and environmental engineering at Purdue University in 2007 and 2010, respectively. As he moved through all three degree programs, he took time in between to work for an environmental consulting firm, Greeley and Hansen in Chicago, IL. He is currently an Associate and the San Francisco Office Director with Greeley and Hansen. We sat down with Ray to find out what his experience has been like since completing the BIOTRANS program. Here’s that reflection:
STAFF: Looking back, how have things turned out since completing your Ph.D.? RAY: The fact that I was part of the BIOTRANS Ph.D. program helped me out a lot because my background focused on the civil and environmental engineering side. I think the reason that I went back [to school] was because of my interest in research and academia in general. The ability to get into research outside of what I saw as typical engineering research was valuable, and I wanted to learn from different perspectives. It was great to work with different people at Virginia Tech and in BIOTRANS and learn, not just research-wise, but how they worked on a day-to-day basis and how they balanced work and life—things that were as important to me as my research. S: What do you do now at the firm? R: Greeley and Hansen is an environmental consulting firm that develops innovative engineering solutions for a wide array of water, wastewater, water reuse, solid waste, and odor/air challenges aimed at improving public health, safety, and welfare. A lot of the work that I did [in my Ph.D.] was focused on air quality, so I now work in a similar capacity by gathering data, evaluating situations, and designing the most appropriate solution for our clients. We work collaboratively with utilities worldwide to identify, evaluate, and design the process, technology, or approach that improves the water or air quality for them as well as the communities and people that they serve. S: How do you see your BIOTRANS experience play out as a consultant? R: I’ve learned a lot about how to communicate with different individuals through the BIOTRANS program. Because of my civil and environmental engineering background, working within Dr. Schmale’s group allowed me to further develop my ability to communicate and work with different people outside of my field of expertise. Beyond working in Dr. Schmale’s
“Working with other people was a big help because I was out of my [academic] realm, so learning from my advisors and my lab members was something that broadened my understanding of my project as well as those of the lab members who were involved. And, since I knew what other people were working on, I was able to put the whole picture together.”
lab, my background in my own discipline was based more in water and wastewater, so joining Dr. Marr’s Applied Interdisciplinary Research in Air group, was yet another opportunity to learn. Working with other people was a big help because I was out of my [academic] realm, so learning from my advisors and my lab members was something that broadened my understanding of my project as well as those of the lab members who were involved. And, since I knew what other people were working on, I was able to put the whole picture together. Ultimately, I gained the capacity to listen, to understand, and to learn. From both my advisors, I learned effective communication, time management, and to value people’s time. Those are important lessons I will always carry with me. On the research side, I did modeling, air quality monitoring, statistical evaluation, and data analyses during my degree. I still use a lot of this in my day-to-day job with Greeley and Hansen, and I think it provides value and helps drive decisions because the data is what the data is, it tells the story and presents itself. A lot of this kind of training during my Ph.D. translated over to what I’m doing now. S: What did your research show when you finished? R: My research focused on understanding the spread of a disease that impacts agriculture around the world and what conditions cause that disease. I was not just looking at it from a correlation standpoint, but was trying to identify a causal agent; we looked at whether a variable, like relative humidity, was shown to be the causal agent for the release of a spore that caused this fungus to proliferate in the atmosphere. We used this causation analysis to identify specific meteorological parameters that were causal agents that may, in turn, be useful in predicting the release of a spore and, therefore, the spread of this disease. S: Can you give me an example of something from this research that plays out in your work now as a consultant? R: I think a lot of the causality analyses—if you know what is causing another event, then this is really valuable for what I do. We’re looking at large cities, we’re looking at treatment, we’re looking at nutrients associated within these areas, and discharges like those into rivers and larger bodies of water, so we are always looking at how to improve water and air quality for everyone. And not just drinking water from the treatment plants, but also ecosystems that are receiving streams of treated wastewater. I think a lot of our work is identifying whether something is going to impact an ecosystem and people. S: What advice would you give to potential students who are considering this program? R: Because the BIOTRANS program focuses on unknown areas and because it’s not a traditional program where you focus within a department, my advice would be to remain flexible in understanding and opening yourself to new ideas. My projects were not something that a civil engineer traditionally would focus on, you know? We focus on areas that are traditionally assumed to be in our realm. In this program, you don’t have those boundaries, and I think many of us went to school for our undergrad and master’s within departmental silos, so we become predisposed to thinking in that box to some degree. The program gave me time to open myself up to this, and being able to understand that this could be a really cool project but it’s going to take some time to work out. Because of this, though, there’s more leg work on the front end that has to be done to get up to speed.
poster sessions, and realize you are a bit of an outlier, and I always had to explain more to others who were not familiar with the topics. But I think this provides a new opportunity, an avenue for exploration. Also, there are a lot of faculty and trainees from various departments in BIOTRANS, so take time to get to know them because they are all unique and it’s a positive and familylike environment. At the end of the day, the fact that I was in the BIOTRANS program helped out a lot in terms of creating that level of camaraderie and support that’s required as you are progressing through your degree. S: What’s your favorite part of your current job? R: I really like working with young engineers now, and I think that’s the big reason I liked research and teaching while at Virginia Tech. I enjoyed the mentoring aspect and working on a team and helping students find their trajectory. It is always exciting to work with them until it really clicks. Then they start to do a lot of these things on their own and this provides a level of content, something really beneficial that came out of working with them.
Interview has been edited for reading ease.
For me, that leg work was all the biological impacts and fungal life cycles, including how this disease spreads. A lot of that is not what I was exposed to previously, so I had to be open to the idea that I was not walking into a traditional Ph.D. You’ll look around at your departmental
Fralin Life Science Institute Fralin Hall West Campus Drive, Room 101 Virginia Tech 0346 Blacksburg, VA 24061 540-231-6933 (v) 540-231-7126 (f)
Cell imaging from the Cimini lab. Image courtesy of Daniela Cimini.
Editor: Kristin Rose Volume 3