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Localization of the Insulin-sensitive Kv1.3 Ion Channel During Brain Development

Ion channels are membrane proteins that control neuronal activity. Kv1.3 is a specific ion channel that is sensitive to the hormone, insulin, suggesting that this channel may play a role in regulating metabolic function. The purpose of this Charles A. Dana Research Fellowship was to localize Kv1.3 ion channels in the hypothalamus, a region of the brain specialized in regulating energy homeostasis. These experiments confirmed that Kv1.3 is expressed in specific hypothalamic areas governing food intake and energy expenditure during development, suggesting a role for this channel in the early patterning of metabolic circuits. Overall, understanding the role of insulin-sensitive Kv1.3 channels in brain development may provide a target for therapeutic intervention for metabolic disorders such as diabetes and obesity.

Dana Research Fellowships
These fellowships, supported by endowed funds from the Charles A. Dana Foundation, are awarded to tenure-track faculty on a competitive basis to support research, creative, or scholarly projects.

BY SEAN MARKEY | Office of Academic Research Annual Report

Summer 2017

It’s a Friday lunch hour, and seven Army veterans filter into a second floor gym at a Vermont National Guard armory on the Norwich campus. Many of the men and women have served tours in Iraq and Afghanistan, and all have been wounded or injured while on duty.

Athletic trainer Carrie Beth Pine, a 36-year-old Army veteran and mother of two, writes the day’s workout in black magic marker on a mirrored wall. As her smartphone pumps out a 30-year pop playlist on portable speakers, the wounded warriors chat and ease into Pine’s workout.

As the hour progresses, Pine—a Norwich triple major—offers encouragement over kettle ball squats and inverted rows. “Is that an extra [rep]? Are you doing something extra?” she says, keeping a sharp eye on her charges.

A middle-age Army vet (name withheld for privacy) pulls up during a Hungarian lunge. After 20 years of active duty, including tours in Iraq and Afghanistan, he is 50 days from retirement. He shares that his knee is sore. “How about we do front raises instead?” Pine says, suggesting he switch to a weightlifting arm exercise. “That way you’re not aggravating the hell out of your knee.” If not for the Army t-shirts and tight haircuts, the workout could resemble any lunch-time corporate wellness program. But there’s some serious science behind the sweat.

The wounded vets are participating in a study called the Collegiate Warrior Athlete Initiative. The protocol is designed to learn whether a “buddy system” that partners college athletes with wounded warriors can effectively engage veterans to improve their physical and mental health and help them reintegrate into civilian life.

Today’s group, the third and final cohort of the year-long study at Norwich, is one month into their 12-week program. The volunteer subjects have signed up for 150 minutes of exercise per week, Fitbit activity tracking, and weekly TED-talk-style lectures to spark their minds. Topics range from nutrition and meditation to plate tectonics and love poetry.

NU researchers are also recording benchmark physical and mental health indicators at the one, six, and twelve-week mark. These include BMI (body mass index); a self-report RAND sleep survey; and the 21-question Beck Depression Inventory to assess mood.

Norwich School of Nursing Director Paulette Thabault, DNP, APRN-BC, FAANP, is leading the study with help from nursing faculty colleagues Llynne Kiernan, PhD, RN-BC, and Lorraine Pitcher, PhD, RN. Their work is part of a broader study developed for Boston College by retired Army Col. Susan Sheehy, PhD, RN, and led by principal investigator Ann Burgess.

“We have a lot of military, who come back from deployments… with a variety of injuries,” Thabault says, speaking in her basement office in the NU Bartoletto science complex. “Historically, there have been some challenges around reintegrating them into society.”

For many veterans, those challenges extend beyond physical injuries. Thabault says many experience post-traumatic stress, sleep disorders, anxiety, and difficulty reestablishing their relationships.

The Wounded Warrior Project, a national nonprofit founded in 2003 to help injured servicemen and women, estimates that more than 54,000 U.S. service members have been severely wounded in conflicts since 9/11.

An additional 300,000 service members have suffered traumatic brain injuries during that period, while 400,000 experience some form of post-traumatic stress disorder.

The nonprofit awarded a $250,000 research grant to support the Collegiate Warrior Athlete Initiative study, which Boston College investigators invited Norwich to join.

A large and growing body of research continues to highlight the link between exercise and improved physical and mental health. Part of the work of the wounded warrior study at Norwich and Boston College explores needs matching.

“We have warriors all over the country,” Thabault explains. “We have universities and colleges all over the country” with workout facilities and potential volunteer pool of student athletes.

“If this could be a national model, it would be just a great opportunity for us to really address our warriors.” That is the vision of the study’s principal investigator Ann Burgess.

Kiernan, an assistant professor at the Norwich School of Nursing, says she and her study colleagues are looking to foster engagement. “We’re trying to get the warriors engaged in a weekly workout routine. With that, we’re hoping that improves their mood and maybe other aspects of their life.”

Early signs suggest the program has already helped many participants. Thabault says warriors set personal goals at the beginning of the program, and many have achieved them. “That’s been really important,” Thabault says.

One warrior in the Boston College program, for example, had trouble with his back. “His individual goal was to be able to lift up his small child,” Thabault says, adding that by the end of the twelve-week program, he could.

While Norwich researchers have enlisted two to three NU students as volunteers for each study cohort, there haven’t been enough for a true 1:1 “buddy system.” So they modified the protocol to create a group circuit workout model. The change appears successful, with vets working out as often as five times a week.

Back in the Vermont National Guard armory gym, the wounded warriors gather to share a few thoughts at the end of their Friday workout. “It’s easier with the group motivation,” says one female Army captain. “Otherwise, I’d be like [stuff] it.”

“I have less aches and pains than when I started,” says the male vet with the sore knee. He adds that some lecture topics didn’t sync with him, meditation in particular. But a middle-aged Army colleague disagrees. He says he’s already applied some of the meditation tools discussed to improve his sleep.

The warriors also talk about the general wear and tear that active duty in a war zone imposes on a human body. Performing as many as two to three daily missions “outside the wire” of their base, soldiers carry 120 pounds of body armor and rucksack gear.

Then there are the countless hours spent slamming over war-torn, third world roads in military vehicles with rough suspension.

“Without looking at the specific data results, we have noted that our warrior athletes are able to recover from some of the wear and tear of the battlefield,” says retired Air National Guard Lt. Col. Kim Swasey, who was forced to end a 26-year-military career after breaking her neck.

Swasey participated in the first cohort of the Collegiate Athlete Warrior Initiative at Norwich last summer and has since stayed on as a workout buddy and research assistant. Swasey says the program helped her recovery. “[It] put [me] back on a path toward physical and mental fitness,” she says.

Norwich and Boston College researchers gave a podium presentation on their research and findings at the April 2017 Eastern Nursing Research Society Conference in Philadelphia.

“By shifting my focus to include Alzheimer’s, I am placing myself at the forefront of current research, especially that which uses mathematics to better understand this disease.” – Joe Latulippe, PhD

When associate professor of mathematics Jocelyn (“Joe”) Latulippe first submitted his research proposal as an application for the 2016 Board of Fellows Faculty Development Prize, he didn’t anticipate that he would win. Nor did he imagine that his proposed investigations would yield potentially game-changing ramifications in the field of Alzheimer’s research.

But he did. And they have.

Latulippe’s specialty is mathematical neuroscience: a branch of the discipline that uses computational methods to advance researchers’ understanding of the human nervous system and the mechanisms of neuron activity. In outlining his winning project, titled Modeling the effects of synaptic plasticity on the firing patterns of neurons, Latulippe proposed three key objectives: to develop a working mathematical model that could explain how the brain’s synapses transmit signals from one neuron to the next; to more firmly establish an interdisciplinary community of neuroscientific researchers at Norwich University; and to actively engage undergraduate students in cutting-edge research.

Today, he has not only made significant progress toward those goals—he has also opened a broader investigation into how neurons communicate under the influence of specific organic diseases. The early results of this work place him, and Norwich University, at the vanguard of research into a universally devastating illness.

An Unexpected Tangent

For Latulippe, arriving at this point was a somewhat happy accident. Although he had earned his PhD studying mathematical neuroscience from the University of MontanaBozeman in 2007, he had drifted away from it in the years since.

After spending four postgraduate years as associate professor of mathematics and statistics at California State Polytechnic in Pomona, he joined the Norwich faculty in 2011 as a generalist. Which is not to say he eschewed scholarship; on the contrary, he has submitted more than a dozen peer-reviewed papers on diverse topics such as differential equations, dynamical systems, perturbation methods, inquiry-based learning and writing in mathematics.

“I came to Norwich because it was a place I knew I could advance my scholarship, and grow as a teacher and a researcher,” Latulippe says.

As it turned out, the Board of Fellows competition reignited his first scholarly passion in ways that have already demonstrated significant promise.

“I’ll be honest; when I considered the proposal I might write, I first thought of my dissertation,” he recalls. “And when I thought about that, I got really excited. There are so many unanswered questions in neuroscience, and so much potential in applying mathematical models to the study of neurons and how they function. I realized that I was ready to jump back in.”

Mathematical Modeling and Organic Disease

In order to understand the connection between Latulippe’s work and Alzheimer’s disease, it is first necessary to understand the applications of mathematical modeling in normal neuronal function.

“Biologically, the process of this reaction is extremely complex,” Latulippe explains. “But from a mathematical perspective, it’s simple: a signal arrives at the synapse; something happens; and then a new signal travels to the next cell.”

At its base level, then, a synaptic transmission model is a quantitative tool for describing exactly what happens when neurons fire—and allows researchers to study the effects of certain stimuli, such as light patterns, on that process.

Latulippe’s original intent was to improve upon existing synaptic transmission models through incorporating the idea of plasticity—a term that describes a synapse’s ability to adapt to specific signals. More simply put, he sought to devise a tool that could help explain what variables might strengthen or weaken a synapse over time, and how.

Drawing upon hypotheses originally proffered in his dissertation (A Non-autonomous Phenomenological Bursting Model for Neurons), and with the assistance of a Norwich undergraduate, Latulippe succeeded in developing a “validated model”—one based on known experimental data—that enables researchers to test the behavior of neurons and synaptic transmission under the influence of specific conditions.

And this is where things got interesting: because the link between synaptic transmission and neurological diseases such as Alzheimer’s is inextricable.

“Alzheimer’s is the manifestation of breakdowns in memory, learning, and cognition,” Latulippe explains. “In other words, Alzheimer’s patients experience a progressive loss of synaptic plasticity. We know that one of the hallmarks of the disease is the development of plaques and fibrils known as amyloidbeta (Aß) peptides; what we don’t know is what triggers their development in the first place.” Latulippe’s newly developed model enables investigators to simulate exactly what happens to neural pathways and synaptic transmission at the very onset of Alzheimer’s disease—before the imminent proliferation of plaques and fibrils.

The benefits of such an approach are clear. With the click of a mouse, mathematical models can change the conditions of an experiment by controlling for individual mechanisms, such as the effect of calcium on Aß peptides, at will. Unshackled by the limitations of time or the bureaucracy of human trials, such simulations provide reams of data in the few short minutes—or seconds—it takes to run them.

“By shifting my approach to include Alzheimer’s,” Latulippe says, “I am putting myself at the forefront of current research, especially that which uses mathematics to better understand the evolution of the disease.”

At the conclusion of his project, Latulippe expects to submit two peer-reviews articles for publication: the first, based on a mathematical model that captures synaptic plasticity; the second, characterizing the firing patterns of single neurons.

Engaging the Norwich Community

Along with the student who helped Latulippe develop his model, he has involved four undergraduates in his Board of Fellows project— with plans for more, thanks to continuing support from the Vermont Genetics Network.

“Although mathematical modeling comprises many advanced topics, undergraduate students with a basic understanding of differential equations can become active researchers,” he says. “In my opinion, opportunities like this—to interact across the spectrum of theory and practice—is what undergraduate research is all about.”

Noting the significance of Norwich’s recent addition of a neuroscience major, Latulippe is also working with resident neuroscientist and biology professor Megan Doczi to organize a collaborative community of faculty and students in the fields of biology, chemistry, physics and math. Although a work in progress, Latulippe’s vision for its mission is clear.

“To do this kind of research, you need broad-based expertise,” he says. “Working together through interdisciplinary interactions will put Norwich’s programs at the forefront of desirability for students, and will contribute to a vibrant scholarly environment for our faculty. The way this work is unfolding, there will be plenty of ongoing research opportunities here at Norwich for years to come.”

In addition to his current investigations in mathematical neuroscience, Latulippe teaches undergraduate courses across the mathematical spectrum, including calculus, discrete mathematics, computational theory, statistics and operations research. He serves as assistant coach of the men’s lacrosse team; holds a 2nd-degree black belt in Akido; enjoys painting and drawing (some of his work is on display at Norwich); and makes time for “fun” side projects with colleague Dan McQuillan. Currently, the duo is preparing a paper, How to shovel snow all winter without lifting, that demonstrates, through physics, a safer approach to moving the white stuff.

“I value being well-rounded, and am always seeking opportunities to grow as a person, teacher, and scholar,” he says.

“There’s this misconception that some people are good at math, and some people aren’t. But the truth is, it’s a continuum. There are many, many skill sets required to be a really good mathematician; I just happen to have some of them.”

Dan McQuillan, PhD patiently walks a visitor through his area of expertise— topological graph theory—with a collegial tone signaling his confidence that even an abecedarian can grasp its complexities.

McQuillan’s work utilizes sophisticated mathematics to calculate the crossing numbers of complete graphs embedded on a surface—but McQuillan doesn’t explain it this way. Instead, he invokes common geometrical shapes to illustrate the precise area of his inquiry.

“Imagine the vertices of a square as people, and the lines between those vertices as relationships,” he begins, conjuring a simplified version of a graph Facebook might use to represent its subscriber base. “Now, imagine drawing the two diagonal lines between opposite corners; this symbolizes the full complement of possible relationships among the people.”

He continues, “It’s my job to figure out, in any given graph, how many edge crossings there are—the point where those diagonal lines meet in this example— and whether there’s a way to reduce them. Why? Because there are concrete instances where such crossings are undesirable: when you’re designing an electrical circuit, for example.”

Aha: his visitor understood. This pleases McQuillan.

“If you can view math as a language, and you know what the words and sentences mean, then it becomes much more fun and meaningful!” he says.

Indeed. In conversing with McQuillan in English, his knack for teaching math as a second language becomes immediately clear, and for good reason: he has been speaking mathematics fluently since 1989. That year, as an undergraduate student at Carleton University in Ottawa, Canada, he co-authored his first paper with mathematics professor R. Bruce Richter titled On the Crossing Numbers of Certain Generalized Petersen Graphs. This seminal event launched a career of inquiry into a topic McQuillan remains immersed in today.

A pure Mathematician

McQuillan is a pure mathematician: a scholar involved in basic research for which there may be no immediate, or even future, application. As such, he feels fortunate to be at Norwich.

“A lot of the best research has no grander intent than to ask questions simply for the sake of asking them,” he explains. “Yet many decision-makers don’t understand this. At Norwich, I don’t have to justify everything that I do. The leadership here supports the value of investigation, regardless of outcome.”

One of McQuillan’s current queries is, “How many edge crossings are possible for a complete graph with 15 points?”

“We literally do not know the answer,” McQuillan says. “It becomes mathematically impossible to avoid edge crossings in complete graphs with as few as five points; with 15, no one can conceptualize what’s going on. Even a computer can’t. That’s what I’m working on right now.”

McQuillan can’t say whether the results of this work will be useful in his lifetime. But the fact that it might—even a century from now—is precisely the reason he perseveres.

“The way most difficult problems are solved, in any field, are by using things that people didn’t originally think would be part of the answer,” he says. “Yet the ‘publish or perish’ culture of academia often pressures researchers to seek straightforward projects. I am extremely grateful to Norwich for encouraging me to take significant risks. That’s when truly special work emerges.” A genuine collaborator

“Since Dan first arrived at Norwich 15 years ago, he has raised the collective level of scholarship within the mathematics department,” says Dave Westerman, Charles A. Dana Professor of Geology and Vice President for Research at Norwich.

McQuillan, as humble as he is brilliant, demurs.

“There’s this misconception that some people are good at math, and some aren’t. But it’s a continuum. There are many, many skill sets required to be a really good mathematician; I just happen to have some of them.”

If McQuillan is missing a particular skill set, it’s hard to identify. A prolific author, he has published several impactful papers in topological graph theory, as well as in the diverse areas of discrete mathematics, linear algebra, and calculus. His article On the Crossing Number of K13, also co-authored with B. Richter and S. Pan, has ranked number one on Science Direct’s list of “hottest papers.”

Adept at identifying his colleagues’ complementary competencies—and regularly seeking their counsel on particularly difficult questions—McQuillan has co-authored several articles with Norwich faculty as well, including department chair Rob Poodiak, Darlene Olsen, and Jeremy Hansen. He also has a paper in progress with Joe Latulippe.

“When you see mathematics everywhere, then it’s easy to engage with your colleagues in creative ways. Sometimes, those conversations lead to a publication. But it’s important to note that this is not particular to me. Our entire department is very receptive to starting interesting discussions to see where they lead.”

An inspiration in the classroom

A passionate teacher and mentor, McQuillan regularly brings his research into the classroom—using it to catalyze students’ understanding of complex concepts, and to spark investigations of their own.

Recalling his own experience as an undergraduate, when he often didn’t fully grasp the material until years later, he strives “to be aware of what sorts of things take time to sink in, and what will be helpful to students a decade from now.”

By equipping students to solve problems through real-world examples, as opposed to memorizing equations just to get through the course, McQuillan hopes his approach to teaching will have a lasting impact.

This is another area in which he believes Norwich shines.

“Small class sizes offer the opportunity to experiment,” he says. “When I use my work to illustrate the application of a particular topic, I know right away whether or not it ‘clicks’ with the students,” he says. “That level of interaction doesn’t exist in 500-person lecture halls.”

Nor, perhaps, would the opportunity to publish as an undergraduate—something McQuillan actively encourages. To date, he has co-authored four peer-reviewed publications with Norwich students.

“I challenge students to reach beyond their comfort zones,” he says. “Because truthfully, there are unsolved questions in mathematics where undergraduates know enough to contribute to their solutions,” he says.

McQuillan also believes that Norwich undergraduates are fully capable of considering problems at the highest level, and signals this through his oversight of the university’s participation in the annual Putnam Competition—considered one of the most prestigious mathematics tests in the world.

Looking ahead

Raised in Ottawa, McQuillan earned his master’s and PhD degrees in mathematics from the University of Western Ontario. He joined the Norwich faculty in 2002 after serving as a visiting assistant professor at Lakehead University in Ontario, and a lecturer at Southern Illinois University at Carbondale.

Since his arrival, McQuillan has taught 17 different mathematics courses, often carrying a full load. He has mentored 20 students in their summer research and independent study projects.

Noting the importance of long-term research goals, he is excited to be developing the concept for a textbook on the process of mathematical problem-solving with Norwich colleague (and former student) Addie Armstrong. In the more immediate future, he anticipates (within two years) the publication of “by far the best” paper he’s ever done with international collaborators B. Richter, Alan Arroyo and G. Salazar.

In recognition for his outstanding research, scholarship and teaching, President Richard M. Schneider named McQuillan as a Charles A. Dana Professor—the first in Mathematics since the award’s inception in 1974—during Commencement on May 14, 2016.

“My best work has occurred since joining the Norwich University community,” McQuillan says. “And I believe that—thanks to the support I receive here— even better work lies ahead.”

Norwich University officials announced top positions filled:

Provost and dean of faculty: Norwich has named Sandra G. Affenito, Ph.D., as new provost and dean of faculty beginning August 1, 2017. Affenito holds a doctorate in nutritional sciences from the University of Connecticut and she completed postdoctoral training in biomedical and behavioral sciences at Wesleyan University through the National Institutes of Health, Office of Women’s Health.

As a 2012 alumna of the HERS (Higher Education Resource Services) Institute for Women in Higher Education Administration, Wellesley College and a 2015 graduate of the Institute for Management and Leadership in Education at Harvard University, Affenito has extensive background experiences in higher education leadership and management. Collectively, she has more than 35 years of leadership and administrative experience in higher education, health care, and the corporate sector; this background has provided for diverse leadership experiences across a variety of functions and units.

Chief information officer: Norwich has named Francis (Frank) Moore, of Spanaway, Washington, as chief information officer at Norwich University beginning July 5, 2017. Since 2000, Moore has served as the chief information officer at two universities: Longwood University, Virginia. and Pacific Lutheran University, Washington. At both institutions, he handled information technology services budgeting and strategic planning. Besides performing the traditional chief information officer duties at Norwich University, Moore will teach several computer science and computer security and information assurance classes.

These two positions are newly created.

“With the addition of these two positions to our university leadership team, we are well positioned as an institution to deliver a world-class education to our future leaders as we usher in our bicentennial in 2019 and envision the next phase of Norwich University,” President Richard W. Schneider said.

College of National Services dean: Norwich named Air Force Col. Andrew Hird (pictured) as dean of the College of National Services, which oversees Reserve Officer Training Corps (ROTC) programs at Norwich through the departments of Army Military Science, Aerospace Studies and Naval Science.

Hird is Commander of U.S. Air Force ROTC Detachment 867, Northfield, Vermont., where he leads and manages the administration of the Air Force officer training program at Norwich University. Detachment 867’s nine authorized personnel guide and mentor approximately 150 officer candidates, active and special cadet students through training and professional leadership development as well as instruction in Air Force structure, history and national security affairs.

He has commanded aircrew in the C-141B and C-17A, and is a former C-17A schoolhouse instructor. He has served on the Air Staff, the Central Command Combined Air Operations Center staff and the United States Transportation Command Staff. Besides his current command, Hird commanded the 62nd Operations Group, 517th Firebird Airlift Squadron and the 385th Air Expeditionary Group. He is a Command Pilot with over 5,000 flying hours and has flown combat missions in Operations Deliberate Force, Allied Force and Enduring Freedom and Iraqi Freedom.

About Norwich University

Norwich University is a diversified academic institution that educates traditional-age students and adults in a Corps of Cadets and as civilians. Norwich offers a broad selection of traditional and distance-learning programs culminating in Baccalaureate and Graduate Degrees. Norwich University was founded in 1819 by Captain Alden Partridge of the U.S. Army and is the oldest private military college in the United States of America. Norwich is one of our nation's six senior military colleges and the birthplace of the Reserve Officers’ Training Corps (ROTC). 

Norwich will celebrate its bicentennial in 2019. In fulfillment of Norwich’s mission to train and educate today’s students to be tomorrow’s global leaders, Norwich launched the Forging the Future campaign in 2014. The five-year campaign, which is timed to culminate in 2019, is committed to creating the best possible learning environment through state-of-the-art academics and world-class facilities and is designed to enhance the university’s strong position as it steps into its third century of service to the nation.

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