Notre Dame Science 2019 - Chemistry and Biochemistry Excellence

New hope for the treatment of diabetic foot ulcers

Community research collaboration creates better system for treating trauma patients

American Chemical Society conference draws teachers from across nation


New hope for the treatment of diabetic foot ulcers

By Sarah McCafferty

In America, more than a million people suffer from diabetic foot ulcers.

In Latin, SalvePeds means “saving feet.” 

And in SalvePeds, a new IDEA Center startup managed and marketed by a team of graduate students at the University of Notre Dame, patients may soon have a more effective option to treat diabetic foot ulcers and prevent some of the 100,000 amputations the condition necessitates every year.

An estimated one in four diabetes patients will develop foot ulcers during their lifetimes. Diabetic foot ulcers are notoriously difficult to heal, often resulting in lower-limb amputations. The wounds do not heal properly because of a protein that results in prolonged inflammation, and current treatments do not address this root problem. 

Mobashery And Chang At Computer

The topical gel, ND-336, developed by Notre Dame researchers Mayland Chang, professor of chemistry and biochemistry, and Shahriar Mobashery, professor of life sciences addresses the underlying condition by counteracting that protein, thus inhibiting the breakdown of tissue so the wound can heal. The compound was developed in the labs at Notre Dame, and is currently being tested in preclinical animal trials. 

“Cognizant of the unmet clinical need surrounding the effective treatment of diabetic wounds, we directly addressed the issue of why diabetic wounds are difficult to heal through pharmacological intervention,” Shahriar explains. “This was the scientific genesis and foundation of SalvePeds.” 

The only currently approved drug, Regranex, has modest efficacy and comes with an increased risk of cancer and mortality — on top of the already high one-year-mortality rate of diabetic amputees, sitting currently around 50%. 
SalvePeds presents a new solution to this problem. Early pre-clinical results show the topical gel to be 150% more effective than Regranex, and 200% faster than a placebo. 

“I am interested in studying diabetic foot ulcers for personal reasons,” Chang said. “My mother and aunt who took care of me as a child so that my mother could help my father in the family business both had diabetes and died prematurely. My sister has diabetes and I am prediabetic. I hope that our compound can make a difference in the lives of patients with diabetic foot ulcers.”

The head of SalvePeds is Notre Dame graduate student Trung Nguyen, a PhD candidate in biochemistry who has been working with Drs. Chang and Mobashery for five years to develop the drug. Also on the management team are Raja Krishnan, an MBA student with a BS in Chemical Engineering, an MS in Pharmaceutical Science and an MS in Law; and Melissa Connolly, an ESTEEM student with a background in biochemistry. 

With diabetes rates nearly doubling in the past two decades, from 5.5 percent of Americans in 1994 to 9.3 percent in 2012, the Centers for Disease Control and Prevention predicts that one in three American adults will suffer from this disease by the year 2050. As the number of patients with diabetes continues to rise, so will the occurrences of diabetic foot ulcers – and so will the number of people who could benefit from this product.

The company is currently initiating an Investigational New Drug application with the Food and Drug Administration, and plans on being in phase I clinical trials as early as 2019. They are in the process of actively raising funds to help carry out these clinical trials.  

SalvePeds has progressed to, and is competing in, the second round of the McCloskey New Venture Challenge at Notre Dame. SalvePeds was also recently invited to the Rice Business Plan competition, the world’s richest and largest startup competition, where they are set to compete from April 5-7 in Houston. One of 42 teams selected from a 375-applicant pool, SalvePeds is the only team from Indiana chosen to compete for $1.9 million in prizes in front of 300 judges, a panel that includes angel investors, venture capitalists, CEOs, industry specialists and NASA special judges. 

“It is extremely difficult to get selected for the competition as a pharmaceutical startup, and we are excited for this amazing opportunity to showcase the research and entrepreneurial spirit at Notre Dame,” Nguyen said.  


Community research collaboration creates better system for treating trauma patients

By Brandi Klingerman

Trauma, or any kind of severe physical injury, continues to be today’s leading cause of death for people 46 and younger in the United States. In 2007, Dr. Scott Thomas and Dr. Mark Walsh of Memorial Hospital in South Bend were looking for a better way to treat trauma patients who arrived in the emergency room (ER) with excessive bleeding. Their search eventually led to a translational research collaboration with the W. M. Keck Center for Transgene Research at the University of Notre Dame and the development of a new method for treating trauma patients.

Upon arrival to an ER, about 25 to 35 percent of seriously injured trauma patients have excessive bleeding, or coagulopathy, without clotting. Traditionally, coagulopathy could be treated with fluid resuscitation, but Thomas, chief of trauma services for Beacon Health Systems, and Walsh, an ER physician, knew that a blood replacement product – like platelets, plasma, or cryoprecipitate – would be a better treatment option. 

Professor Francis J. Castellino

However, each patient has individual blood replacement product needs, and there was no standard method for determining those needs in a trauma setting. After speaking with other medical professionals, they realized a machine called the thromboelastogram or TEG, used to test the efficiency of blood coagulation for transplant and cardiac surgery patients, could be used in the ER to look at coagulation profiles. 

“This had never been done before,” said Walsh. “From that point, we began to consider how that work could be translated in different ways, but knew we would need a research arm to support this effort.”

Walsh and Thomas reached out to Francis J. Castellino, Kleiderer/Pezold Professor of Biochemistry and Director of the Keck Center, who they knew studied the functions of components of the hemostasis system – or the process that causes bleeding to stop – in a variety of genetic diseases. Castellino worked to develop a model for Thomas and Walsh that helped determine which replacement blood product was needed for treating a trauma patient who wasn’t clotting properly.

Eventually, the team received a research grant from Memorial Hospital, and Haemonetics Corporation donated TEG machines for the project. With data from Col. John Holcomb, M.D., one of the military’s top medical surgeons who met with the research team in 2009, the team found that the TEG’s ability to map platelets allows any given trauma team the ability to more effectively manage blood products for resuscitation of patients who are bleeding out. 

“When our initial studies were being published in 2011, most trauma centers had not yet adopted the use of TEG machine analysis,” said Thomas. “However, because of this collaboration with Dr. Castellino and his team, we were better prepared here in South Bend than many other trauma centers in the country with this technique.” 

From here, the collaboration expanded to other areas of trauma care and blood coagulation. For example, Castellino developed models for a number of studies including one for analyzing blunt traumatic brain injury (TBI) that represented coagulopathy. TBI is a contributing factor to a third of all injury-related deaths in the U.S., and acute coagulopathy is a serious complication for this injury.

“Our goal was to develop a model of TBI that mimicked the condition observed in people so that a procedure for treating patients with TBI would be readily understood,” said Castellino. “This is just one example of how Dr. Thomas, Dr. Walsh, and I were able to establish a translational research collaboration and because of the partnership with Memorial Hospital, which is nationally recognized for providing a high level of trauma and surgical care, as well as being a leader in innovation, we get to see how this research directly and positively impacts the community.”

This TBI research also led to an additional study funded by the Indiana State Department of Health and the National Heart, Lung, and Blood Institute and published in the American Journal of Physiology in 2016. The groundbreaking results showed that patients may incur lung injury following TBI because of biological events including the release of tissue factor, a protein that triggers blood clotting. Together, the research team has published about 15 papers on the topic of blood coagulation, resuscitation, and the use of TEG in successful trauma care. Now, Thomas and Walsh are working on establishing guidelines and protocols for transfusing patients and for using the TEG machine to treat trauma patients with their established, goal-directed model.

“There were a lot of factors that fell in to place and allowed this collaboration to work, but it has given Dr. Thomas and myself an opportunity to have a greater impact in our field and all over the world,” said Walsh. “Without the advantage of Notre Dame’s research infrastructure, the ‘right-size’ of the local community, and Castellino’s expertise and team, we wouldn’t be where we are today.”

The W.M. Keck Center for Transgene Research at the University of Notre Dame develops models as well as uses gene-targeting technology to investigate the roles of genes for blood coagulation for embryonic development, cancer, stroke, infection, and more. To learn more about the center, please visit transgene.nd.edu

Memorial Hospital provides the highest level of newborn and pediatric care, cancer care, trauma care, surgical care, and rehabilitation care in the region. Memorial Hospital of South Bend is a community-owned, not-for-profit corporation based in South Bend, Indiana. It is governed by volunteer representatives of the community guided by a mission to improve the quality of life for the people of our community. To learn more, please visit https://www.beaconhealthsystem.org.

 


American Chemical Society conference draws teachers from across nation

By Ellen Crowe Finan

In July, 1,700 college, high school, and middle school chemistry educators from across the country attended the American Chemical Society’s 25th Biennial Conference on Chemical Education (BCCE) hosted for the first time at Notre Dame.

BCCE Conference Sam Kean

“This was the largest BCCE overall, and it was the largest academic conference ever held at Notre Dame,” said Steven Wietstock, conference program chair and associate teaching professor/teaching lab safety coordinator in the Department of Chemistry and Biochemistry at Notre Dame.

Participants presented nearly 1,400 papers and 125 workshops. Topics centered around chemical education research, including information on how students learn and how to apply that to teaching.

The BCCE also featured four plenary sessions with speakers who are renowned in their field. Marcy H. Towns, a professor of chemistry and the director of general chemistry at Purdue University kicked off the event. A long-time chemical educator, Towns received both the ACS Award for Achievement in Research for the Teaching and Learning of Chemistry and the most prestigious award the ACS offers for excellence in teaching.

“This conference represented 50 years of chemical education,” said Wietstock. “We wanted to look back and into the future of our field. Marcy Towns has a long history in the field and the ACS.”

The five-day conference provided teachers the opportunities to network, share and gather new ideas, and learn about what their colleagues are doing in the classroom. Participants presented nearly 1,400 papers and 125 workshops. Topics centered around chemical education research, including information on how students learn and how to apply that to teaching, explained Wietstock.

Penny Snetsinger, who teaches introductory and advanced chemistry at Sacred Heart University in Fairfield, Connecticut, has been attending the conference for 27 years. “I get a lot of great ideas from the symposiums for engaging my students in active learning the classroom,” she said. “I’m the only physical chemist at my college, so I really enjoy talking to other colleagues, too”

Monday morning, participants heard Notre Dame faculty Jennifer Tank, professor of biology; Marya Lieberman, professor of chemistry and biochemistry; Ryan Roeder, professor of aerospace and mechanical engineering; and Paul Bohn, professor of chemical and biomolecular engineering, share how their scientific research impacts communities across the globe.

Conference speaker Dr. Jacob Clark Blickenstaff, a passionate advocate for overcoming socio-economic, ethnic and gender barriers in teaching science to help all students have access to high quality science education, addressed the group on Tuesday morning about challenging binary thinking in education. Dr. Blickenstaff has an unconventional role in promoting science education equity – as a movie critic in “Blick on Flicks,” a regular column in NSTA Reports.

Popular science writer and author Sam Kean, the author of four books, including The Disappearing Spoon, entertained and delighted the crowd with fascinating tales about some of the elements on the periodic table. “Stories always stuck with me,” said Kean. “The periodic table is one of the richest sources of stories out there.”

Denver high school chemistry educator Amy Hanson was thrilled to have the opportunity to hear Kean speak after reading his book The Disappearing Spoon. And as a teacher of introductory chemistry and advanced placement (AP) chemistry, she appreciated the mix of high school and college faculty at the conference. “I like all the new ideas I learn about at the conference,” she explained. “And I also like talking to college educators about what they are teaching students in their classrooms, because that’s where my AP students will be headed soon.”

The planning committee provided opportunities for fun and relaxation, too. In addition to a golf outing and a food truck extravaganza, “Al D. Hyde and the Key Notes,” a band formed by chemical educators, entertained conference participants with their high-energy performance.

Over the years, non-tenure track teaching faculty have become more mainstream in top-flight institutions like Notre Dame, Wietstock explained. “We are all chemical educators who work in the classroom, and we are not doing research,” he said. “This conference is a great opportunity to get to know others doing the same thing and showcase our innovative teaching methods and learn from our colleagues at other institutions.”

Conference participants were drawn to Notre Dame’s central location and its beautiful campus, said Wietstock. “It was also a chance for Notre Dame to show that the University has the capability to and the facilities to host very large academic conferences in the future.”