Cancer Researcher Describes the Power of Breakthroughs

Cancer researcher and entrepreneur Pinku Mukherjee says seed money from grants and gifts drives UNC Charlotte’s ability to innovate and create knowledge. Through the university’s Exponential campaign, the College of Liberal Arts & Sciences seeks support for this type of work.

Study Characterizes Key Molecular Tool in DNA Repair Enzymes

New research by UNC Charlotte scholar Shan Yan and colleagues has revealed the function of a widely shared enzyme component, the Zf-GRF domain, as a critical molecular tool necessary for manipulating DNA during repair processes.

A living organism’s DNA needs constant maintenance. Every cell is in a state of fierce siege, as plentiful reactive oxygen compounds and ions constantly assault and damage the cell’s organic molecules, especially its DNA. Oxidative damage to DNA is estimated to occur 10,000 times per day per cell.

For life to survive this molecular battlefield, molecular countermeasures have evolved, among them a suite of complex molecules that detect oxidative damage to sections of DNA molecules, targeting those areas with various repair molecules that perform a series of elaborate molecular engineering operations necessary to fix the problem. The intimate mechanics of the complex molecular assemblies dedicated to the recognition, repair and signaling of DNA damage are still not fully understood.

A specific protein structure known as the Zf-GRF domain is a mysterious component of APE2, a DNA-repair and DNA damage response enzyme, and is also common to a number of other DNA-maintaining molecules.  A new research finding shows that Zf-GRF performs a critical DNA binding function in helping enzymes properly align to single-stranded DNA. The new study appears in a paper published online in The Proceedings of the National Academy of Sciences (PNAS) on December 27, 2016.

The finding is a result of two teams, one headed by Yan, a faculty member in the Department of Biological Sciences in UNC Charlotte’s College of Liberal Arts & Sciences. The second is headed by R. Scott Williams from the Genome Integrity and Structural Biology Laboratory at the National Institute of Environmental Health Sciences (NIEHS) in the National Institutes of Health.

“We study APE2, which plays an important role in repairing DNA following oxidative stress,” Yan said. “We are trying to understand the structure and function of this enzyme because it’s not very well characterized, but plays a central role in the cellular response to oxidative DNA damage.”

APE2 has different domains, he said. “One of the least understood is called Zf-GRF, which we have succeeded in characterizing,” he said. “We found that its function is to interact specifically with a single strand of DNA. If this domain does not bind to the single strand of DNA, APE2 doesn’t promote its catalytic activity and it cannot move forward in the appropriate 3’ to 5’ direction along the strand. ”

The Zf-GRF domain, Yan said, is also found in several other proteins. In all cases, it has a “claw-like” structure and other protein components surrounding a zinc molecule that are nearly identical in all cases or “highly conserved.”

“Though it’s a very small domain – about 50 amino acids – it’s highly conserved in evolution,” he said. “This enzyme domain is the same across many species, which implies that it’s important. It is also found not only in APE2, but also in many other enzymes, including important DNA metabolism enzymes such as Topoisomerase 3α and NEIL3. Our finding can be applied to future studies on those proteins.”

The ubiquity and uniformity of the Zf-GRF structure is explained, because this molecular tool plays a very useful and critical role in the control of enzymatic activity, Williams said. “The APE2 DNA processing activity is necessary for activation of “cellular checkpoints”, an alarm which is signaled when DNA damage is detected, and helps to prevent further damage from occurring, while making it possible for a cell to fix these toxic lesions,” he said. “If left in an unrepaired and un-signaled state, such oxidative DNA damage can be a major contributing factor to cancer progression, amongst other maladies.”

Authors of the paper, titled “APE2 Zf-GRF facilitates 3’-5’ resection of DNA damage following oxidative stress,” are Bret D. Wallace, Geoffrey A. Mueller, Timothy Chang, Sara N. Andres, Jessica L. Wojtaszek, Eugene F. DeRose, C. Denise Appel, Robert E. London, and R. Scott Williams from the Genome Integrity and Structural Biology Laboratory at NIEHS/NIH, and Zachary Berman, Yunfeng Lin and Shan Yan from the Department of Biological Sciences at UNC Charlotte.

The research was supported by funds from UNC Charlotte and NIGMS/NIH (grant numbers R15 GM101571 and R15 GM114713) and NIEHS/NIH (grant numbers 1Z01ES102765 and 1Z01ES050111).

Words: James Hathaway | Image: Lynn Roberson

From Planets to Microspheres: New Optical Devices Target Real-World Problems

When Vasily Astratov explains complex principles of physics, specifically in the world of optics, he turns to St Paul’s Cathedral in London and its Whispering Gallery. Whisper on one side of the iconic dome, and someone standing a hundred feet away on the other side can hear the whispered words.

“The dome or spherical shape helps trap the sound inside the cavity and transmits it around the inside surface,” says Astratov, a professor in the Department of Physics and Optical Science. “The same principle is at work in optics.”

Optics involves the study of light. Instead of a large cathedral dome, think of a microscopic sphere. “A different form of wave – electromagnetic – traps visible light in much the same way acoustic waves trap sound,” he says. “Just as the cathedral can trap sound, a microsphere can trap visible light.”

However, there is one important difference with the acoustic waves. The light trapped in microspheres has an evanescent component – a kind of “cloud” extending from the microsphere, very much like an atmosphere on a planet. When the light wave resonates inside the sphere, this cloud becomes thicker and it extends longer. This electromagnetic cloud is extraordinarily sensitive to variations in the microsphere environment. More than a decade ago, researchers Stephen Arnold and Frank Vollmer suggested using such evanescent clouds for sensing of individual protein and viruses.

It has become apparent that the applications of this phenomenon are unlimited, Astratov says. “One of the lines of thinking in the modern optics community is that this evanescent field can also help us see extraordinary small details of the objects in the atmosphere of the microspheres, which are not ordinarily seen in standard optical microscopes,” he says.

Knowledge of this phenomenon and its implications for scientific research have propelled Astratov to submit patents on optical components that use microspheres to provide super resolution capabilities – one with his former student in 2012 and another with his Air Force Research Lab collaborators in 2015. Astratov, a native of St. Petersburg, Russia, received his doctoral degree at the Ioffe Institute, one of Russia’s largest institutions for research in physics and technology, part of the Russian Academy of Sciences and a home institution for several Nobel laureates.

It was there in the mid-1990s that he pioneered studies of synthetic opals as novel three-dimensional photonic crystals for visible light.

A leader in his field of study, Astratov has named a new field of study, microspherical photonics, to describe the research directions of his group. In microspherical photonics, individual spheres are focusing and trapping light, and they “whisper to each other” due to an overlap of their evanescent electromagnetic clouds.

“There are many applications where you need extreme accuracy, such as precise laser surgery to attach a retina or remove a fibrotic membrane, for example,” he says. “We want to explore the many applications.”

Since joining UNC Charlotte in 2002, his work in the field has yielded several technologies – the new optical device and laser scalpels to focus laser beams, for example – with four patents and two more pending.

The new optical devices take the study of light to a new level, moving into the realm of photonics which, simply defined, is a combination of optical science and engineering. The optical devices based on microspherical photonics promise to deliver a cost-effective solution to physicians, scientists, lab technologists and others who want to improve the performance of their microscopes and their diagnostic capabilities.

“Optical microscopes are fundamentally limited in their resolution due to diffraction of light,” Astratov says. “The outer edges of an object remain blurred when viewed through a microscope. Use of these evanescent electromagnetic fields and our new optical component helps overcome that limitation.”

In Astratov’s lab, doctoral student Aaron Brettin leans over a microscope, carefully placing a sample under its objective lens. The optical component, made from elastomeric transparent material with embedded barium-titanate glass spheres, looks like razor thin sheets or microscope coverslips. By placing them over the sample, the microspheres are as close as possible to the objects to be viewed, catching their evanescent electromagnetic fields and allowing greater resolution capabilities, an enhancement for imaging biological structures.

According to Astratov, these new coverslips with embedded spheres help scientists view not just the cellular level but also to resolve the subcellular structures, a critical component in biomedical research. While numerous industries such as pharmaceutical, semiconductor, optoelectronics, computer chip and, especially, microscope manufacturing companies, may benefit from the work in Astratov’s lab, the biomedical area is what draws him the most.

“The application I find most exciting and practical is the potential use by pathologists and histologists,” he says. Physics, in this case microspherical photonics, gives insights into diseases by helping pathologists more readily see the subcellular level of human tissues, proteins, bacteria and viruses.

In initial research with pathologists at a nearby hospital, Astratov and his team received valuable feedback to take back to the lab to improve their process. “By gaining insights into the methodology entailed with their diagnostic processes, I was able to extrapolate new ways to improve our own product fabrication,” says Kylen Blanchette, a senior physics and mathematics major.

While higher resolution is available with scanning and transmission electron microscopes, Astratov says that they have their drawbacks. “They are expensive, they require a high level of training, and they also destroy cells,” he says.

Even though the standard optical microscopes have less than optimal resolution due to the diffraction limit, doctors prefer them. This is why the new optical components hold great promise for the industry. Astratov is working with the UNC Charlotte Research Institute and the Office of Technology Transfer to form SupriView, a company that will manufacture and sell microsphere-embedded slabs.

He also plans to expand the technologies related to microspherical photonics, including further development of ultra-precise laser scalpel technologies for tissue surgery and new ways for sorting dielectric microspheres by using their resonant whispering gallery properties.

The latter technology is based on breakthrough research in his lab devoted to observation and study of the giant resonant light forces in microspherical photonics, highlighted in Optics & Photonics News as one of best achievements in 2013.

His innovative laser scalpel technology received a prize in 2013 in the Charlotte Venture Challenge, a competition for early-stage high growth companies. Through the National Science Foundation Industry/University Cooperative Research Center on Metamaterials, his team receives funding from the Air Force Research Lab, part of the U.S. Department of Defense.

Astratov’s team relies on the fabrication facility at AFRL to develop the nanoplasmonic arrays or objects that are used in super-resolution studies. They also work together to publish results of their research, and AFRL has for many years provided summer student internships.

Astratov and doctoral student Farzaneh Abolmaali will present designs of their optical devices in early 2017. Astratov is a program committee member of a subconference on Nanoscale Imaging, Sensing and Actuation for Biomedical Applications and an invited speaker at Photonics West, the world’s largest event focusing on photonics technologies, including medical technologies and smart manufacturing.

Abolmaali says she selected physics, specifically optics, “where the fundamental knowledge of light can be connected with engineering and technology and then becomes practical.” The new optical device, Abolmaali says, “is an example of how optics bridges science and engineering.”

For Astratov, the device serves as an inspiration for his continuing research into how microspherical photonics can help solve real-world problems.

Words: Leah Chester-Davis | Image: Lynn Roberson

CMS Teachers Study With Researchers in CTI Initiative

Teachers lay the foundation for students to understand and embrace science. This significant role holds true whether the students aspire to scientific careers or simply need as citizens to understand how scientific research can help their everyday lives.

Despite their critical role, teachers often find themselves limited in their exposure to the settings where scientific research occurs.

Charlotte Teachers Institute has worked with UNC Charlotte professors Susan Trammell and Marcus Jones to address that gap. Through a pilot program called the Summer Research Experience for Teachers, Charlotte-Mecklenburg Schools teachers collaborated with professors and graduate students in UNC Charlotte lab settings for the first time in summer 2016.

“I wanted to give teachers a first-hand look at what it is like to be a scientist,” says Trammell. “The teachers that I worked with come from many different grade levels and will prepare the scientists of the future. However, most of them have never been in a research lab and do not really know what it is like to ‘do science’ as a career. This is information that they need, to help inspire and guide their students.”

The summer initiative was a first for CTI, which is an educational partnership among Charlotte-Mecklenburg Schools, UNC Charlotte and other universities that works to improve teaching in Charlotte-Mecklenburg public schools.

“CTI is all about bringing together university and college professors to collaborate and co-create with classroom teachers,” says CTI Executive Director Scott Gartlan. “This program is no different. This experience for teachers cultivated their curiosity, creativity and knowledge of cutting-edge scientific techniques.”

The initiative came together because of converging interests, Gartlan says.

“Marcus Jones initially reached out to CTI to support his proposal for a NSF CAREER award,” he says. “Dr. Jones and I decided to include stipends for teachers to participate in a summer research experience in his university laboratory working alongside his graduate students.”

Meanwhile, Trammell, a three-time CTI seminar leader and CTI University Advisory Council member, also wanted to broaden her research agenda to include science teacher education, a passion of hers for years.

Trammell with teachersIn each lab, Trammell and Jones provided guidance for the partnership. Graduate students educated teachers on laboratory protocols and scientific principles, as well as helping them develop curricula for later use in their classrooms. The teachers expressed surprise – and gratitude – for the important role that graduate students played in the labs and in their collaboration.

“As a graduate student, my duties included overseeing safety procedures and daily lab maintenance,” says Drew Tobias, a Nanoscale Science doctoral student in Jones’ lab who worked with the teachers, along with fellow student Kathleen Dipple.

“But my role ultimately became one of a mentor,” Tobias says. “We were able to keep the teachers engaged and productive, and they were excited to be here. I think they gained insight into actual experimentation and can better relate what we are doing to general life.”

Jones’ efforts with the teachers drew from his current CTI long-term seminar, called “It’s a Small World!” which draws upon themes from his NSF-funded research. “Nanomaterials could provide a pathway to cheap and abundant renewable electricity,” Jones says. “In that context, we discussed the need for sustainable energy and the economic and environmental factors that are driving the search for alternative sources.”

Coulwood Middle science teacher Joyce Patton describes the experience and its lingering impact as amazing.

“The summer experience in Dr. Jones’ lab was inquiry learning done right,” Patton says. “Engaging, inspiring and by far the best educational experience I have ever had. It was so inspiring I was able to work with a local scientific equipment company, CEM Corp., to donate a single-mode focused microwave unit. This will allow my students to safely synthesize nanoparticles, right in the classroom.”

UNC Charlotte’s Trammell also turned to her CTI seminar, which is titled “How Science is Done,” providing a behind the scenes look at university research and the scientific method. Doctoral candidates Joseph Peller and Madison Young joined her in coaching teachers in the lab.

Trammell’s research concentrates on biomedical applications of optical techniques, imaging and spectroscopy in particular. Projects in her lab include building a new camera that can be used for cancer detection and developing a method to preserve proteins that are used in diagnostic tests.

“It was great experience for the teachers as they learned lab work is not as formulaic as standard teaching labs would apply,” Peller says. “They encountered problem after problem, yet continued to work rigorously until they resulted in success.”

Two undergraduate students who were conducting research through the Charlotte Community Scholars program joined the team, working with CTI as interns. Political science and economics student Anthony Ellis and psychology student Kenia Rios were part of a 9-week research experience that provides students with an immersive engaged scholarship experience to address community needs.

Ellis with professor“Over the summer I worked directly with CTI to analyze six years’ worth of data to see if the program has caused any impact,” Ellis says. “I’ve gained tons of experience working with abstract quantitative data, and now have an idea on how we can use it to improve future programs.”

Since its inception in 2009, CTI has conducted 60 long-term seminars led by 46 Davidson College and UNC Charlotte professors for more than 400 CMS teachers, totaling over 17,000 hours of professional development. The summer experience provided another avenue for exposing teachers to intense professional development.

“The teachers developed a deeper understanding of university-level scientific research, methodology, and laboratory equipment and practices,” Gartlan says. “In turn, they will develop curricula that motivates and excites their students to see the essence of scientific inquiry more as a process of discovery than as a set of rules to follow.”

Words: Tyler Harris and Kendra Sharpe | Images: Lynn Roberson
Top Photo: Doctoral student Andrew Tobias (left) works with CMS teachers Joanne Rowe and Joyce Patton. Second photo: Professor Susan Trammell (second from right), doctoral student Madison Young (left) and teachers Miesha Gadsden, Tabitha Miller, Connie Wood. Third photo: Student Anthony Ellis (right) describes his undergraduate research with CTI as a Charlotte Community Scholar.

Arbor 49er Project “Speaks for the Trees” on Campus

“I speak for the trees, for the trees have no tongues. And I am asking you at the top of my lungs.”

Many of us recognize this quote from Dr. Suess’ book The Lorax from when we were young, but as we grow up we often forget to notice the trees. One exception may be during the fall when the leaves begin to change colors. After all, the fall foliage in the mountains of North Carolina is well known for its astonishing beauty.

That is why I have waited to introduce people to the Arbor 49er project until now, when they are paying extra attention to the trees. You may have noticed the colors, but do you know what kind of trees they are? Do you know anything about them? Do you realize what are they used for? Can you make tea from their flowers? What is that one with the heart-shaped leaves called?

If you have noticed tags hanging from the trees on campus, they are a large part of a local tree project I created on campus to maximize student-ecosystem interaction. As part of the project, students in my Ecology Labs and I chose 49 select separate tree species and took photographs of characteristic features and an overall shot of each tree.

We marked their coordinates with a GPS program and put those coordinates into Google Earth. We wrote a description of characteristics and any notable historical background for each of the 49 trees. This resulted in an interactive map with the exact location, pictures, and characteristics of each of the trees.

On my faculty webpage you can download the map that was published by Google Earth with the trees labeled or unlabeled, in a scavenger hunt format. I use the latter to help teach students tree identification in some of my field courses.

Next, my students and I labeled the physical trees. With help from UNC Charlotte Facilities Management, we obtained money to order bronze placards for each of the 49 trees and establish a fund for their replacement.

As a continuation, in the last phase of the project, we combined the physical and virtual worlds by creating scannable QR codes that allow the campus and broader community to scan each tree and read about their significant characteristics. Once the leaves have fallen, the corresponding information will also allow everyone to see what the trees look like in the summer.

Next time you’re waiting around for your next class to start or passing through campus while enjoying the autumn breeze, if you notice a tag, use that smart phone and scan a nearby tree. Not only will it give you a mental break, but it will foster the kind of appreciation the Lorax always wanted us to have.

As we feel each of our summers grow hotter than the last, we have become more aware of the importance of conservation. And it all starts with the appreciation of our immediate surroundings.

Because, to quote our friend the Lorax, “Unless someone like you cares a whole awful lot, nothing is going to get better. It’s not.”

I would like to thank Joey Cochran for funding the project, Paula Gross with the UNC Charlotte Botanical Gardens for double checking all the labels, my buddy Dan Rubin for telling me I should label the trees on campus to begin with, and Brittany Raines for making all of the QR code cards.

Words: Aaron Kampe, Biological Sciences lecturer | Image: Lynn Roberson

Jones Named Bank of America Teaching Award Finalist

Associate Professor of Chemistry Daniel Jones is among the five finalists for one of the University’s highest honors – the 2016 Bank of America Award for Teaching Excellence.

He joins the other award finalists Anita Blanchard, associate professor of psychology and organization science; Matthew Davies, professor of mechanical engineering and engineering science; Jae Emerling, associate professor of art and art history; and Janos Gergely, associate professor of civil and environmental engineering. The 2016 recipient will be named on Friday, Sept. 9.

In a 43-year career at UNC Charlotte, Jones has taught more than 5,000 students. Throughout these years, his teaching philosophy has been student-centered and holistic. While Jones sees it as his responsibility to assist in a student’s intellectual growth and academic success, he also acknowledges that teaching in the classroom is inseparable from his own learning and personal growth.

“It is especially important that I learn from my students, something which I do nearly every day,” Jones said.

Jones encourages student collaboration and engagement by creating an active learning classroom environment; he also is committed to involving students in research.  According to Jones, the way he and his department colleagues conduct research is teaching.

Jones’ research involves the determination of molecular structures by X-ray crystallographic methods. He involves both graduate and undergraduate students in every aspect of this research, including data collection, data analysis, structure determination and manuscript preparation. In fact, since obtaining his research equipment in the 1980s, all but one of his scholarly publications have had one or more of his students as coauthors.

Known as “Diet Coke Man” to his students, Jones receives strong praise from students in the introductory chemistry courses, especially from those students who might not have taken chemistry previously or who are deathly afraid of chemistry.

Bernadette Donovan-Merkert, professor and chair of the Chemistry Department, said, “Dan has an approachable, calm demeanor that puts students at ease. He is patient with the students and makes chemistry relevant to their interests.”

Her comments are echoed by students. Freshman pre-nursing major Jillian Teeter stated, “As a freshman taking a chemistry course, I was worried about not adjusting well and struggling. Professor Jones has made my transition into college courses very smooth. He teaches with passion and cares genuinely about his students learning the material, not just passing the course.”

By focusing holistically on the intellectual development of his students, Jones hopes they develop the “lifelong process of thinking critically and asking and answering important ethical and moral questions.” For Jones, the best embodiment of this process is UNC Charlotte’s University Honors Program.  One of his most-lasting contributions to UNC Charlotte is his role in establishing an honors program.  In 1982, Jones co-wrote a proposal for a university-wide Interdisciplinary Honors Program, which became active during the 1983-84 academic year. Jones sees his long-standing involvement in honors education at UNC Charlotte as “one of the most important if not the most important” aspect of his academic career.

Jones recalls that in Chaucer’s “Canterbury Tales,” the Oxford clerk said that “gladly would he learn and gladly teach.”

“I can think of no greater accolade,” said Jones, “and I would be both honored and humbled if I were to be found worthy of this description.”

Retired Botanical Gardens Director Receives Excellence Award

Larry Mellichamp, retired director of the University’s Botanical Gardens, received the 2016 Tom Dodd Jr. Award of Excellence at the Cullowhee Native Plant Conference held at Western Carolina University in late July, 2016.

This annual award celebrates the North American Native Plantsman of the Year and is presented to individuals who have actively worked to conserve native flora in situ, study and promote the understanding of native flora, build expertise in the propagation/cultivation of native plants and use native plants in a diversity of natural and designed landscapes. It has been presented since 1988.

Currently president of the North Carolina Native Plant Society, Mellichamp was recognized for his dedication to the study, propagation and promotion of the native plants of Southeastern North America.

“Larry Mellichamp excels in all of these categories and is truly deserving of this award,” says Jeff Gillman, director of the UNC Charlotte Botanical Gardens.

The Cullowhee Native Plant Conference began in 1984 with a grant from the Tennessee Valley Authority to underwrite a “Plant Utilization” meeting. Since then the combination of field trips, workshops, lectures and social networking opportunities have become a model for similar native plant gatherings across the country.

The namesake of the Dodd Award was a well-known Alabama nursery owner who studied ornamental horticulture at Auburn University. His strong interest in plants led him to travel throughout the United States and many foreign countries in search of unusual native plants that could be adapted to Alabama. Dodd served in various leadership positions in the Alabama Nurserymen’s Association, South Alabama Botanical Society, Garden Club of America, American Association of Nurserymen and the American Horticultural Society.

Mellichamp joined UNC Charlotte in 1976 as a faculty member in the Biological Sciences Department, retired in spring 2015. He authored several works, including Native Plants of the Southeast, and a number of technical and popular articles on plants and gardening.

UNC Charlotte Botanical Gardens Celebrate 50 Years With Symposium

Gain an intoxicating perspective on the leaves, bark, seeds, roots, flowers and fruit imbibed around the world when Amy Stewart, best-selling author of The Drunken Botanist: The Plants Amy StewartThat Create the World’s Great Drinks, keynotes a UNC Charlotte Botanical Gardens’ 50th Anniversary Symposium on Saturday, October 8, 2016.

Attendees also will learn easy-to- remember garden design strategies for working with such elements as form, texture and color, during a talk by Steve Aitken, editor of Fine Gardening magazine. This symposium also features a look back at the gardens’ history as well as a peek at what is coming next. Lunch and a tour of the Gardens are included.

Doors will open at 8:30 a.m. on the third floor of the Student Union on the UNC Charlotte main campus. Complimentary parking will be available in the Student Union parking deck. Participants will tour the Gardens from 3 p.m. to 4 p.m. Walking shoes are encouraged.

The symposiuSteve Aitkenm is open to the public; pre-registration is required. Register online or call 704-687- 0721 by August 31 to receive the “Early Bird” discount rate for the daylong event. Registration will close October 3.

Begun in 1966 on the newly-established Charlotte campus of the University of North Carolina system, the Botanical Gardens were the brainchild of biology professor Herbert Hechenbleikner and UNC Charlotte founder Bonnie E. Cone. The gardens serve as a living classroom for biology students and as a horticultural and botanical resource for the campus and greater community.

As landscape manager, Hechenbleikner began growing unusual native plants on UNC Charlotte’s young but growing campus; this led to the development of the Van Landingham Glen, a seven-acre garden of hybrid rhododendrons and native plants of the Carolinas. Today, the Botanical Gardens include 10 acres of outdoor gardens, a 4,500-square- foot glasshouse with attached workspace, and a classroom that also contains a botanical and horticultural library of more than 1,200 books. More information can be found on the gardens’ website.

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Researcher Uncovers Clues to Cancer, Neurodegenerative Disorders

Frogs and their tiny eggs are helping a UNC Charlotte researcher unlock the mysteries of genomic instability, with implications for cancer and neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease.

Biological sciences assistant professor Shan Yan researches DNA damage that human cells sustain from thousands of internal and environmental assaults each day. Researchers know that the body’s cells have a complex set of processes that constantly assess the damage and make repairs to fragile genetic material.

Yet, the vital biochemical processes by which this constant DNA repair takes place are still only partially understood because of their complexity, speed, and the difficulty of studying complex interactions within living cells. Moreover, it remains unknown how cells sense the oxidatively damaged DNA in the first place.

“The main question we try to answer is how genomic integrity is maintained,” Yan says. “All living organisms have a genome, which must maintain its integrity in response to damaging agents, such as oxidative stress or chemotherapy drugs. The process is not well studied and there are many unanswered questions, which is why we are interested.”

For organisms to maintain their integrity, an elaborate network called DNA damage response detects abnormal DNA structures through a process called checkpoint signaling and coordinates the repair and activation. This DNA damage response has been demonstrated as a biological barrier to the formation of tumors.

In an article published in the Proceedings of the National Academy of Sciences (PNAS) in 2013, Yan’s lab first announced the discovery of a previously unknown surveillance mechanism.

Two biochemical pathways, known as ATM-Chk2 and ATR-Chk1, govern the cell’s response and repair of double-strand DNA breaks and other types of DNA damage or replication stress respectively. The molecular mechanisms underlying the ATR-Chk1 checkpoint activation include the uncoupling of DNA helicase and polymerase activities and DNA end resection of double-strand breaks.

The UNC Charlotte researchers found a third, previously unknown trigger for ATR-Chk1 checkpoint pathway, and this novel mechanism was discovered in the context of oxidative stress.

A base excision repair protein known as APE2 plays unexpected roles in the checkpoint response: single-strand DNA generation and Chk1 association. The protein was previously known to be involved in the DNA repair of oxidative damage, but not to the extent revealed in the study’s findings.

“Better understanding of these processes can give us new clues or avenues for therapies for human diseases,” Yan says. “We have discovered that many of the target proteins we’re working with in Xenopus are correlated with those found in cancer patients.”

Yan’s research is funded in part by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS). The funding (NIH R15GM101571) has allowed Yan to support his lab, train students, and publish eight papers in a three-year period, often with students.

The most recent research papers were published in Biochemical and Biophysical Research Communications and Cellular Signalling. Yan also summarized the current understanding of oxidative stress response and discussed applications of these findings from basic research to cancer and neurodegenerative diseases in two comprehensive review articles in Cellular and Molecular Life Sciences and International Journal of Molecular Sciences.

In March 2015, the NIH awarded him additional funding of over $360,000 (NIH R15 GM114713). He also has received funding from UNC Charlotte.

“The whole research program is growing, and we are grateful for the funding support,” Yan says. “This is a very encouraging and emerging area, and our cutting-edge research projects will help to better understand genome stability and cancer development.”

Yan works closely with students and fellows, including postdoctoral fellows and graduate, undergraduate and high school students.

“We’re passionate about this line of research because we want to know how it works at the core,” says Steven Cupello, who is pursuing a doctoral degree in biology. “We don’t just get to uncover that DNA repair happens, but also try to unravel the nuanced mystery of exactly how it happens.”

Another student who works with Yan, Jude Raj, was chosen for a 10-week intensive Research Experience for Undergraduates (REU) program funded by the National Science Foundation. This Biology and Biotechnology REU program allowed him to develop lab research skills, continue independent projects, and present the results at various research symposiums.

“After successful months of training, Dr. Yan offered me the incredible opportunity to pursue an independent project,” says Raj, a biology honors student. “I’ve become deeply passionate about molecular biology and fascinated about the invisible, microscopic reactions taking place in living organisms.”

Raj has gained insights not only into the subject but also into research practices. His research presentation was awarded first place in Biological Sciences at the University’s Undergraduate Research Conference in April.

“I think the biggest life lesson I have learned from my research experience is to never quit and keep moving forward, no matter how much you fail,” he says. “Research has had such a great impact on me by increasing my problem-solving skills, and even making my classes more interesting. My ultimate dream would be working alongside other scientists to eradicate disease.”

Yan’s students have created a video and a written resource for the Journal of Visualized Experiments, describing how the lab use Xenopus egg extracts to study pathways of DNA damage response. Yan’s lab also shares its research by giving tours of the lab during the UNC Charlotte Science and Technology Expo each spring.

To expand access among a larger group of students beyond his lab, Yan integrates his research in the classroom. By sharing real-world examples of cell biology research outside the textbook, he hopes to inspire his students.

“Science is always the driving force for the overall human being,” he says. “It’s not always easy to move forward, but every new discovery through basic research could open unidentified and unexpected new avenues.”

Words: Tyler Harris | Image: Lynn Roberson, showing Biological Sciences researcher Shan Yan and master’s degree student Stephen Cupello in Yan’s lab.

 

 

 

Mukherjee Receives National Award for Making a Difference in STEM Fields

UNC Charlotte distinguished cancer researcher Pinku Mukherjee has received a 2016 Inspiring Women in STEM Award from INSIGHT Into Diversity magazine, the largest and oldest diversity and inclusion publication in higher education. The Inspiring Women in STEM Award honors women who work to make a difference in the fields of science, technology, engineering, and mathematics (STEM).

Mukherjee will be featured, along with 65 other recipients, in the September 2016 issue of INSIGHT Into Diversity magazine. Each award recipient was nominated by a colleague and selected by INSIGHT Into Diversity based on their efforts to inspire and encourage a new generation of young women to consider careers in STEM through mentoring, teaching, research, and successful programs and initiatives.

As the Irwin Belk Endowed Professor of Cancer Research at UNC Charlotte, Mukherjee is transforming the ways in which cancer is diagnosed and treated. She has designed innovative approaches to more accurately detect breast cancer early and is developing targeted therapy and imaging for pancreatic, ovarian and colon cancers.

Mukherjee also is the chair of the Department of Biological Sciences at UNC Charlotte. She collaborates with researchers from across UNC Charlotte and at other institutions, and with students in classroom and lab settings.

This is the latest accolade for Mukherjee, who was honored a year ago with the O. Max Gardner Award – the highest faculty accolade given by the Board of Governors of the University of North Carolina. The award, established by a provision in the will of Gov. O. Max Gardner, recognizes UNC system faculty members who have “made the greatest contribution to the welfare of the human race.”

Mukherjee has secured approximately $7 million in funding and has over 100 peer reviewed scientific journal publications and proceedings. She has participated in several FDA clinical trials from 1998 to 2008 at Mayo Clinic. She was part of the panel of scientists invited to Capitol Hill in 2010, and part of the NIH/NCI Think Tank for Tumor Progression and Metastasis in 2008. She was the spokersperson for Cristie Kerr’s “Birdies for Breast Cancer Foundation” from 2006-2008 and spokesperson for the CARE Foundation from 2004-2006.

She is the founder of CanDiag and is the sole inventor of the CanDiag antibody which has been used to develop early detection blood tests for breast cancer. She received her bachelor’s degree in microbiology from Bombay University, India and her master’s and doctoral degrees in immunology from Brunel University, London, UK.