AIMRC's Faculty Success Center Cultivates Faculty Researchers

"My personal motivation comes from a very close family member having an entirely treatable tumor completely surgically removed," explains Narasimhan Rajaram, the newly minted director of the Arkansas Integrative Metabolic Research Center, or AIMRC. "There were no issues there, but then eventually she passed away because she was treated too aggressively. It's tough to lose someone when the tumor is completely gone and is not coming back, but she succumbed to the disease because the treatment affected important organs." 

Yet one family's tragedy can provide the inspiration to help another. Rajaram, a professor of biomedical engineering, now hopes to improve tumor diagnosis and ensure optimum treatment protocols are identified much earlier than current practices allow. To do this, he uses optical imaging to study the relationship between tumor oxygenation and metabolism, and its role in promoting undesirable tumor outcomes, such as treatment resistance, recurrence or metastasis. 

"If treatment works, you want to deescalate therapy, if it doesn't, you want to escalate or try a different treatment. The long-term goal is if someone is going to go through radiation or immunotherapy, we make measurements on them before they start therapy," Rajaram elaborates. "During the course of therapy, and within that first couple of weeks, we can then tell the physician: 'This tumor's not going to respond. We have to try something different.' That would be better than the current standard of care, which is you treat them for five to seven weeks, wait another four weeks and then do an MRI, X-ray or CT to identify if the tumor has shrunk or has stayed the same size." 

AIMRC director Narasimhan Rajaram holding a diffuse reflected spectroscopy probe, or “wand.”

By course-correcting weeks or months earlier, crucial time is gained to ensure patients are on the right path to remission.

Rajaram's research interest places him at the core of what has become one of the most quietly successful research centers at the U of A (and in the state). AIMRC's researchers focus on understanding changes in metabolism at the tissue and cellular level and how these changes impact disease, aging and tissue repair. Metabolic dysregulation can also lead to several pathological conditions, such as diabetes, cancer, obesity, wound healing, cardiovascular disease and Alzheimer's. 

Rajaram has been with the U of A since 2014 and with AIMRC since 2021 when the National Institutes of Health made a $10.8 million grant to establish a Center of Biomedical Research Excellence (or COBRE). This program supports states that receive lower levels of NIH funding by helping them create a critical mass of investigators and research infrastructure around a desired focus (in this case metabolism), enabling associated researchers to compete more effectively for independent research funding.

Rajaram takes over at a transitional time for AIMRC. Founding director Kyle Quinn has moved on to Tufts University, while the center is completing the last year of its five-year grant and has applied for critical Phase 2 funding. By any reckoning, the center's first phase has been hugely successful under Quinn's leadership. Affiliated researchers — now 61 people spread across eight departments and five colleges — have won more than $39 million in awards. Of that, new investigators are responsible for an estimated $17.6 million.

A feature of the program is the recruitment and ongoing support of young faculty, with formalized mentoring from more senior researchers. This includes funded positions for four research project leaders, or RPLs, who receive this mentoring, as well as $150,000 a year for up to three years to establish their labs. They "graduate" by receiving a major grant and, ideally, becoming future mentors themselves.

"We want faculty members to come here and get tenure and be really successful because of the support they're receiving," Rajaram says. "If they see themselves being successful and can attribute their success to the presence of this support, they're more likely to stay, right?" 

Right, and maybe even figure out a better way to diagnose and treat various cancers and diseases undermining the health of many Arkansans. 

Engineering Tissues 

Younghye Song, an associate professor of biomedical engineering, was an RPL in the first cohort. Growing up in Korea, Song became interested in bioengineering when she was in high school and learned about Dolly, the first cloned sheep. "I thought it was really fascinating," she says, "and wanted to learn more." As an undergraduate, she worked in a bone tissue engineering lab where they built grafts to treat bone injuries. For her honors thesis she built in vitro mimics of bones using stem cells, and as a Ph.D. student, she worked in a lab using tissue engineering tools to study cancer. Song arrived at the U of A in 2019 as a first-time faculty member and joined AIMRC at its inception in 2021.

Song is now developing naturally derived tissue-based materials that can be used to study the progression of various diseases and promote tissue regeneration without resorting to animal models. These tissue models can help her gain a better understanding of healthy and diseased states, with the ultimate aim of developing novel therapeutics to improve patient outcomes. 

Younghye Song

"Basically, I create cell culture models where the cells are not sitting on plastic but are surrounded by the extracellular matrices that cells in our body innately see," she explains. "These models can give us mechanistic understanding and insights into how disease progresses and what kind of perturbations we can apply to curb those progressions." 

As part of AIMRC's mentoring program, Song was paired with Tim Muldoon, now sole director of the Imaging and Spectroscopy core, and Robert Griffin, a professor in the Radiation Oncology Department at the University of Arkansas for Medical Sciences. They met monthly to discuss the challenges of being faculty: time management, mentoring students, recruiting them to her lab, feedback on drafts of her evolving grant. "Just how to survive this job," Song sums up. "I could reach out to them for anything." 

Song proved a precocious student. Three years after joining AIMRC as an RPL she "graduated," receiving a $2.5 million grant from the NIH to use her tissue engineering approach to study why more nerve fibers are seen in aggressive breast tumors. Ideally, this knowledge will be used to develop new therapeutic strategies to curb metastatic progression.  

Once Song was a senior researcher with a major grant under her belt, she paid it forward by mentoring a junior faculty member in biomedical engineering, Jian Zhang (who has subsequently been awarded a $1.8 million graduating grant from the NIH). 

Song greatly appreciates the process, stating: "AIMRC has been absolutely essential to my lab's existence. The grant would not have been possible without it." 

Muldoon valued the experience, too. "I really enjoyed working with Younghye because she was always very professional, organized and very 'real' with us — unafraid to share the good things and accomplishments, as well as the day-to-day challenges that her group faced," he says. "She's now able to share those lessons learned with other faculty coming through the AIMRC program, which will continue to make our junior faculty extremely successful as they build their careers." 

Lord of the Fruit Flies 

Joining Song in the first cohort of RPLs was Adam Paré, an assistant professor of biological sciences who also joined the university in 2019. Paré attributes his interest in molecular biology to an AP biology teacher he had in high school. She got him thinking about the "exquisitely precise machines that exist inside your cells that perfectly copy these enormous strands of DNA that are billions of nucleotides long. … These astonishingly complex protein machines — I just thought it was so cool." 

In college, his interests shifted to developmental biology, which is the study of how lifeforms develop from a single cell into complex organisms — often containing trillions of cells arranged in precise patterns with dozens of different organs. 

Adam Paré

"All cells have this intrinsic ability to generate force and pull on their own membranes and change their shape and crawl around and do interesting things like that," he explains, painting a picture of cellular activity that's likely far more dynamic than most people appreciate. 

Paré uses fruit fly embryos as a model system for understanding how cells arrange themselves into complex three-dimensional structures along the head-to-tail and body-to-back axes. In particular, he is interested in how genetic information leads to the expression of different molecular signals at the cell surface to control cell shape and behavior. While fly embryos are not as complex as human embryos, most of the underlying processes for organizing cells in space are highly conserved -- and the simplicity of manipulating and observing fly embryos has made them a very popular model system. 

In joining AIMRC, Paré started a new avenue of investigation to study how cellular metabolism is involved in normal development. He saw how his work might overlap with Quinn's, who uses advanced microscopy techniques to study the role of mitochondria and cellular metabolism in non-healing wounds. 

"In wounds, cells have to move around a lot to seal the wound, so it turns out to require a lot of the same genes and proteins that are also necessary for normal cell movements during development," Paré says. "Mitochondria and energy producing organelles located inside cells are critical for both wound healing and embryonic development." 

He also appreciated access to AIMRC's tool cabinet and techniques, which included unusual types of microscopes customized for visualizing cellular bioenergetics. (AIMRC is organized around three core areas of technical expertise: data science, bioenergetics, and imaging and spectroscopy). 

A container of fruit flies.

Like Song, he found the mentoring process helpful: "Some months it was more advice on experiments, others it was advice on hiring people, and other times it was advice on writing or submitting grants." He says the process of mock review panels was particularly helpful, in which the project leaders and their mentors would meet to "tear the grants apart," with the intention of making them as competitive as possible. 

It worked. After several rounds of revision, Paré's graduating grant was awarded in 2023 — $1.55 million to study metabolism during tissue development. He said a previous version of the grant had been denied by the NIH, but support and guidance from AIMRC-affiliated researchers helped shape and accelerate creation of a stronger proposal. He was particularly grateful for the help of managing director, Kimberly Fuller, for her expertise in negotiating the grant process and getting his accounts set up. 

Of the grant's goals, he explains: "This work will give us a better understanding of how groups of cells dynamically rearrange to form complex tissues, and we believe it could also shed light on the underlying causes of certain birth defects, cancer metastasis and impaired wound healing." 

As a graduate, Paré has also taken on a mentoring role, mentoring a junior faculty member in biological sciences, Xuan Zhuang (who also received a $1.9 million graduating grant from the NIH this summer), as well as Jian Zhang. He will now work with assistant professor of biological sciences Amy Poe. 

What's Next? 

As Phase 1 winds down, Rajaram takes the helm of a center already firing on all cylinders. Nevertheless, funding for Phase 2, another five-year period, will be critical to consolidating successes and expanding in terms of infrastructure, instrumentation and personnel, particularly as it provides funding to recruit new faculty and incentivizes the creation of new faculty lines in departments that might not otherwise prioritize metabolic research.  

Ultimately, Rajaram thinks AIMRC can be a national power in metabolic research, one that recruits for itself by creating a gravitational pull that attracts the best researchers from around the world. It can also be a foundation for other centers to spin off. While AIMRC is already united around the theme of metabolism, he would like to see greater concentrations in subspecialties — areas where the center might already have some experts but could attract several more high-caliber researchers tackling problems like sarcopenia (a skeletal muscle disorder often associated with aging), breast cancer or Alzheimer's. In this way, Arkansas could become not just a leader in metabolic research but a leader in the larger arena of human health. 

So, despite already enjoying great success positioning faculty to thrive, they're just getting started.    

AIMRC Core Directors (L-R)_ Suresh Thallapuranam (bioenergetics), Timothy Muldoon (imaging and spectroscopy), and Xintao Wu (data science).