Department of Biomedical Engineering

New Cancer Bioengineering Thrust

Continued inside

Volume 1 • 2016-17

W ith the award of an NCI Physical Sciences of Oncolgy

Center (PS-OC), our research in cancer bioengineering focusing on the biophysics of metastasis has elevated to a new level, as described in the feature article. Another major research award resulting from extensive synergy with our Medical School is an NIH P-50 to establish the UMN Udall Center to integrate neuroimaging, neurophysiology, and deep brain stimulation techniques for improved treatment of Parkinson’s disease. Beyond these two major awards, the other big news, of course, is the 2016 BMES meeting being held right here in Minneapolis. We are excited to have a very strong participation in the scientific program by our faculty and students, the largest exhibit area that we have ever displayed, and the first UMN BME Alumni Reception that we have ever organized at the BMES Annual Meeting. We look forward to seeing many of our more than 1,000 alumni there. Featured inside are profiles of another high-flying graduating senior, another distinguished Ph.D. alumna, and one of the rising stars on our faculty. As always, we look forward to more talent joining our department this year and contributing to our mission!

Head Lines:

Bob Tranquillo, Distinguished McKnight University Professor and Head

Asst. Prof. Paolo Provenzano, Prof. David Odde, Post-doc Brian Castle, Graduate students Horacio Estabrides, Ghaidan Shamsan, Kianna Elahi Gedwillo, Arja Ray, Mackenzie Callaway

C with the patient data, to drive discovery of novel therapeutic targets.

The team is led by BME Prof. David Odde, along with Prof. David Largaespada, cancer geneticist from the University of Minnesota Masonic Cancer Center and Prof. Steven Rosenfeld, neuro-oncologist from the Cleveland Clinic. The “Center for Modeling Tumor Cell Migration Mechanics” will focus on two aspects of migration: the mechanics inside the cell, a project led by Odde, and the mechanics outside the cell, a project led by BME Asst. Prof. Paolo Provenzano. The two projects will work in tandem to develop and test the simulator. In addition, Asst. Profs. Patrick Alford and David Wood co-direct a Microenvironment Engineering core, that will use advanced micro- and nanofabrication methods to create more realistic environments for patient’s cells. Key expertise and guidance will also be provided by BME Profs.

ancer is a disease of abnormally high cell growth and proliferation. When the proliferating cells migrate away from a growing mass of cells and spread out in the body, then prognosis is generally poorer. To address this problem of cell spreading by migration, a group of faculty members from the Department of Biomedical Engineering are working together to develop a better understanding of how cancer cells migrate. Using a physics-based modeling approach, they are developing a “Cell Migration Simulator” that will allow the group to predict how migratory, and therefore how dangerous, a patient’s cancer cells are. Combined with live microscopy and dynamic mechanical measurements on single cells, obtained from patients by biopsy or surgical resection, the group will then parameterize the simulator on a patient-by-patient basis to predict cancer progression. Longer-term, the group intends to use the simulator, combined

Dr. Cindy Clague Cindy Clague graduated with a PhD in Biomedical Engineering from the U of MN in 1994. Her dissertation

work with advisors Perry Blackshear, PhD and Ben Liu, PhD focused on blood trauma and fluid mechanics. As an undergraduate, she received a BS in Mechanical Engineering from Northwestern University. She is currently Research Director for the Heart Valve Therapies business within Medtronic Coronary & Structural Heart. Working at Medtronic since finishing at the U of MN, Cindy has had the good fortune to work on a wide variety of products in which her career has evolved with the technology. Starting in Medtronic’s perfusion business Cindy has worked on blood pumps, oxygenators, blood diagnostics, cardiac stabilizers and positioners, vessel harvesters, anastomotic devices, PFO closure tools and transcatheter heart valves. In her current role, Cindy leads a team of innovative scientists and engineers working in concept evaluation, technical feasibility, new therapy development, anatomical characterization, in-vivo and ex-vivo animal model creation, and valve biomaterials for structural heart therapies. She has more

than 20 issued patents and many pending applications. She was named a Medtronic Technical Fellow in 2007, a Medtronic Bakken Fellow in 2011, a U of MN IEM Industrial Fellow in 2015 and an AIMBE Fellow in 2016.

How did a PhD in BME influence your career path?Getting to spend all my time immersed in biomedical engineering in graduate school felt like a luxury. Biomedical engineering has been my passion since hearing on the news about the first total artificial heart implant. Completing my PhD opened doors for me to pursue my passion in the research end of R&D at Medtronic. My graduate work also kindled the creative inventor in me and taught me to first define the problem and then to identify the key questions to answer. With my training and interests, I’ve sought out the job opportunities that start at the fuzzy front end with a challenge to solve and an unknown answer.

What major changes do you foresee in the medical device industry in the next decade?I see a shift to more personalized devices and to care along the whole continuum from diagnosis to recovery. Custom devices with 3D printing is redefining the trauma care paradigm with patient specific implants created to perfectly match the patient’s own anatomy. Personalized

devices will also be realized by a greater blend of mechanics and biologics in implants for the body to accept readily and to remodel into autologous tissue. Both the advent of personal health monitoring and the increased focus on healthcare costs will drive the need to monitor and care for a patient from beginning to end. Devices will help diagnose, treat and monitor patients throughout their care. Smart devices will also help optimize therapy to deliver the best outcome tailored to individual needs.

What is your advice to BME students aspiring to careers in the medical device industry?Go for it! Working in the medical device industry is amazingly rewarding and fulfilling. At the end of the day, you can feel great about helping people and making a difference for patients and their families. The field is dynamic and ever changing which keeps the challenges fresh and interesting. Be sure to get a strong foundation in one classical engineering discipline but blend it with a solid understanding of physiology and anatomy. Remain curious and inquiring while maintaining the highest integrity in your work because literally a life may depend on it.

Victor Barocas and Robert Tranquillo, as well as University of Minnesota faculty in mathematics, cancer biology, surgery, and oncology. The team will also work collaboratively with clinical oncologists from the Mayo Clinic and the Cleveland Clinic, which will facilitate the ability to integrate the group’s work into oncology practice and drug discovery.

The funding for the center comes from the National Cancer Institute, part the National Institutes of Health (NIH), through the Physical Sciences in Oncology Centers (PSOC) program, and totals $8.2 million

over 5 years. The University of Minnesota PSOC is one of 10 recently awarded centers, along with Columbia, Cornell, Harvard, Johns Hopkins, Methodist Hospital Houston, MIT/Mayo, Moffitt Cancer Center, Northwestern, and Penn. Together the 10 PSOCs will work as a collaborative network, with new projects between PSOCs seeded through the center funding. In addition, the Center will be able to seed new ideas within the University of Minnesota toward the overall goal of suppressing cancer cell migration.

New cancer bioengineering thrust, cont.

Graduate Research Assistant Mahya Hemmat

alumni achievement

FACULTYBin He – IEEE Biomedical Engineering Award

Matt Johnson and Hubert Lim – Promotion to Associate Professors with Tenure

Pat Alford – NSF CAREER Award

Brenda Ogle – Mullen-Spector-Truax Women’s Leadership Award

Bruce KenKnight (Adjunct) – UMN Outstanding Alumni Achievement Award

STUDENTS

Doctoral Dissertation FellowshipsKanchan Kulkarni (Talkachova)

Julia Quindlen (Barocas)

Arja Ray (Provenzano)

Kai Yu (He)

NSF Graduate FellowshipsMackenzie Callaway (Provenzano)

Chris Korenczuk (Barocas)

American Heart Association Fellowships: Xinran “Daniel” Lu (Wood)

Zaw Win (Alford)

Interdisciplinary Doctoral Fellowship: Abbas Sohrabpour

NIH F31 Predoctoral Fellowship: Brad Edelman (He)

First place, PhD Competition in TMM, SB3C: Chris Korenczuk (Barocas)

President’s Student Leadership and Service Award: Amanda Dahl

Amanda just graduated with a Bachelor of Biomedical Engineering degree with an emphasis in Medical Device Design and a Leadership Minor. In her time as an undergraduate, she completed directed research under Professor Erdman, had multiple internships, volunteered for several student organizations, and served as President of the Engineering Student Council. She will be working as a Quality Engineer at St. Jude Medical after graduation.

How did your internships enhance your BME education?Over my collegiate career I had internships at Boston Scientific, Medtronic, and 3M. Having the opportunity to work in the medical device field helped me to understand what type of position I would be interested in after graduation and I was able to customize my classes to fit that. My managers and co-workers from my internships were helpful in giving feedback towards what topics and experiences would aid me in my career. I was even able to become involved in pacemaker lead research at the U because of my exposure to that at my internships.

What was the most rewarding aspect of your student organization involvement?I found the most rewarding aspect of my involvement was being able to take feedback from fellow students and implement it into policies. Not only was it rewarding to see this change enacted, it was great to see other students get excited and wanting to become involved as well. Besides this aspect, the most rewarding experience I had was Co-Directing the National Association of Engineering Student Council’s annual Conference at the U. During this 2-day conference over 300 engineering students from 45 different Universities across the U.S. participated in leadership workshops, learned from local speakers, and discussed strategies to strengthen engineering programs. This was held this past April and was a great way to showcase the U and Minnesota to individuals who had never been here before as well as for me to cap off my collegiate career.

What is your advice for our current BME majors?Get involved in a group or activity outside of classes. Keep your schoolwork as the number one priority, but take the time to go outside of your comfort zone to meet new people and get involved in something you can be passionate about. The U offers a wide variety of opportunities to enrich your college experience, from the BME Society to the Unicycle Club, so take advantage of them.

Amanda Dahl

Alumni, industry and friends play a vital role in enhancing the department’s mission. We hope we can count on your support during the 2016-2017 academic year. Mentoring students, attending BME and UMN events, hosting faculty or students at your organization, and philanthropic gifts of all sizes allow the department to deliver exciting educational opportunities for students, conduct innovative research, and serve the larger biomedical engineering community.

Consider making a gift at http://www.bme.umn.edu. Please contact me to learn how you can strengthen your partnership with BME.

Shannon WeiherExternal Relations612-624-5543 • seweiher@umn.edu

student spotlight news lines

Robert T. Tranquillo, Head7-105 Hasselmo Hall312 Church Street SEMinneapolis, MN 55455(612) 624-4507www.umn.edu/bme

The last decade has seen an explosion in the number of high-resolution structures of proteins. In order to take advantage of this rich library and to engineer novel drug treatments, it is necessary to predict and measure how proteins move. This is a particularly challenging problem in proteins that function within the cellular membrane and are dysregulated in disease.

In Professor Jonathan Sachs’s membrane protein biophysics lab, molecular simulations and experiments in biophysics and cell biology are used to explore important dynamical changes in proteins. Investigations target three distinct disease-related questions. To understand the underpinnings of Parkinson’s disease, the group studies the protein α-Synuclein, which is found in neuronal Lewy body deposits that are the hallmark of the disease (Figure, left). Using molecular simulations, the group has discovered that the protein alters the dynamics, and subsequently the mechanics, of small lipid vesicles, a finding that may explain the protein’s deleterious effects on synaptic vesicle transmission.

The group also studies tumor necrosis factor (TNF) Receptors (Figure, right), involved in a wide-range of diseases, most notably inflammatory diseases (such as rheumatoid arthritis) and cancer. The group has developed a new dynamical model for how TNF-receptors are activated, which is leading to the screening of small-molecules that more effectively inhibit TNF Receptors in disease.

Most recently, the Sachs lab made a fundamental discovery about how oxidation can alter ligand affinity (Figure

right, inset) and also the dynamic transitions between structural states of proteins. Oxidation is a prevalent problem in neurodegenerative disease and cancer, and the new chemistry described by the Sachs group and its collaborators at the University of Minnesota has the potential to open new avenues of therapeutic intervention.

Department of Biomedical Engineering

Nonprofit Org.U.S. Postage

PAIDTwin Cities, MN

Permit No. 90155

Left: A molecular model of the Parkinson’s Disease protein -Synuclein (green) dramatically perturbing the natural structure of its lipid environment; Right: The structure of a TNF-Receptor with a bound ligand, highlighting a critical motif (inset) that is subject to oxidation.

Professor Jonathan Sachs

faculty profile