The University of Cincinnati Cancer Center is committed to developing the next generation of cancer researchers and providers. The Trainee Associate Membership Program offers trainees access to tools and resources to help them be productive and successful cancer researchers and professionals. Trainee Associate Members have access to a community of cancer trainees and mentors, pilot grants, seminar series and educational events, career development opportunities, and more. There are numerous benefits offered to Trainee Associate Members, including:

• Predoctoral Pilot Grants
• Postdoctoral Pilot Grants
• Travel Awards
• Paper of the Year Recognition

In the most recent cycle, nine Cancer Center Trainee Associate Members were selected for pilot project, travel and paper of the year awards. Congratulations to all the awardees!

Pilot Project Awardees

Understanding the Role of pDCs in AML

Chia Sharpe, PhD  Trainee Associate Member University of Cincinnati Cancer Center Mentor: John Byrd, MD

“Acute myeloid leukemia (AML) is an aggressive and hard-to-treat cancer,” said Dr. Sharpe. “It is typically characterized by the uncontrolled growth of blood-forming stem cells that fail to mature, remaining stuck as immature cells unable to perform their normal functions. However, in some AML patients, a subset of leukemia cells closely resembles fully developed immune cells known as plasmacytoid dendritic cells (pDCs).”

Dr. Sharpe and her team are focused on determining whether these leukemia cells are functional as well as how they influence disease progression. Gaining a deeper understanding of the role pDCs play in acute myeloid leukemia (AML) could provide valuable insights into the development of AML and potentially lead to new therapeutic targets.

Acute myeloid leukemia (AML) is a highly diverse disease, both genetically and in terms of immune cell characteristics. While it is often considered a cancer of hematopoietic stem cells, the majority of AML consists of a varied population of myeloid cells at different stages of differentiation. Notably, some patients have AML cells that resemble fully matured plasmacytoid dendritic cells. Dr. Sharpe’s research focuses on understanding the development and function of these cells, as well as their role in sustaining leukemia and contributing to leukemia-driven immune suppression.

“Our laboratory has established a series of mouse models that replicate commonly co-occurring AML driver mutations and discovered that two of these models display a pDC-AML phenotype,” Dr. Sharpe shared. “Notably, we have observed a correlation between pDC expansion and successful engraftment in fully immunocompetent recipients, indicating that pDCs may play a crucial role in sustaining AML in vivo.”

Until recently, AML cells that had matured beyond a stem-like state were thought to be nonfunctional and less critical for leukemia growth or therapy resistance. However, patients with pDC-AML have worse outcomes than other AML patients, raising the question of whether pDCs themselves contribute to leukemia progression.

“Our unique mouse models, including the first preclinical models of pDC-AML, allow us to study the specific role of leukemia pDCs,” said Dr. Sharpe. “We hypothesize that these cells suppress anti-tumor immunity, preventing the immune system from controlling leukemia growth. This study will determine whether pDCs actively drive AML development.”

By examining how leukemia pDCs function compared to healthy pDCs, the team aims to identify the key mechanisms they use to suppress immune responses. The findings will uncover new ways in which AML evades the immune system, potentially leading to targeted therapies that enhance immune responses and improve treatment outcomes for pDC-AML patients.

Receiving this award marks a crucial step in Dr. Sharpe’s journey toward establishing an independent academic career. Beyond recognition, it provides essential support for the early stages of her research, enabling the collection of key preliminary data.

“This award will help support the early stages of a project that will provide the basis from which I will launch my independent academic career,” she shared. “It will provide support for the acquisition of key preliminary data that will form the basis upon which I will apply for further extramural funding.”

Novel Lipid Nanoparticles to Deliver a Hydrophobic Small Molecule Drug into Cancer

Bingxin Liu Trainee Associate Member University of Cincinnati Cancer Center Mentor: Yutaka Maeda, DVM, PhD

“Many promising cancer drugs discovered in preclinical studies fail to make it into clinical environments,” explained Liu. “One major reason is that these drugs are hydrophobic, e.g. do not dissolve in water, and thus, require toxic solvents or extensive chemical modifications to be safely administered. My research addresses this challenge by using lipid nanoparticles (LNPs) as a delivery vehicle for hydrophobic drugs.”

Liu’s Novel Lipid Nanoparticles to Deliver a Hydrophobic Small Molecule Drug into Cancer project focuses on creating and testing an innovative lipid nanoparticle (LNP) system designed to more efficiently deliver the hydrophobic drug iMDK to lung cancer cells in preclinical models. The research team is working to encapsulate iMDK within tiny, specially engineered lipid nanoparticles (LNPs), which will make the drug water-soluble thus reducing the need for toxic solvents and improving its delivery to cancer cells. By improving the efficacy of transport of hydrophobic drugs, this research could transform and advance drug delivery strategies in cancer treatment.

“By overcoming solubility and toxicity issues, our strategy could unlock the full potential of many promising cancer drugs that have previously stalled in preclinical development,” Liu said. “Ultimately, this could lead to more effective treatments with fewer side effects, benefiting patients and expanding the arsenal against cancer.”

For those impacted by a cancer diagnosis, this work highlights the potential for improved cancer therapies with fewer side effects and a better chance of moving from the lab to patient care. By addressing a key challenge in drug development, this approach could significantly impact treatment outcomes for lung cancer and beyond.

For other researchers, the study offers a solution to a major bottleneck in drug delivery by enhancing the solubility and safety of hydrophobic small molecules. With rigorous preclinical testing, including studies on drug-resistant lung cancer cells, this research sets a strong foundation for clinical translation. By merging nanotechnology and oncology, it exemplifies the power of interdisciplinary collaboration in advancing cancer treatment.

More than just an accolade, receiving this award for this project validates years of dedication to overcoming a major challenge in drug development and provides crucial support to accelerate the transition of Liu’s research from the lab to clinical applications.

“This award validates years of hard work and innovative thinking, confirming that the approach I’m taking to solve a major barrier in drug development is both promising and impactful,” shared Liu. “It not only serves as recognition from the cancer research community, but it also provides essential resources that will accelerate the translation of our findings from the laboratory to the clinic. For me, this award is an affirmation that my research direction – bridging nanotechnology with cancer therapeutics – is on the right track, and it motivates me to continue pushing the boundaries of what’s possible in cancer treatment.”

Leveraging PRPS complex to therapeutically target KRAS-mutant lung cancer

Bibek Karki Trainee Associate Member University of Cincinnati Cancer Center Mentor: Tom Cunningham, PhD

Lung cancer remains a leading cause of death, with KRAS mutations being the most common and difficult to target. Current treatments, including targeted inhibitors, have limited success, highlighting the need for new therapeutic approaches.

“My research focuses on developing new treatment strategies for KRAS-mutant lung cancer, an aggressive form of non-small cell lung cancer that is often resistant to current therapies and has a poor prognosis,” said Karki. “Instead of targeting the KRAS mutation directly, which has proven challenging, my work investigates how cancer cells rewire their metabolism to support rapid growth. Specifically, I study an enzyme complex called phosphoribosyl pyrophosphate synthetase (PRPS).”

Phosphoribosyl pyrophosphate synthetase (PRPS) is an enzyme that helps create the molecule phosphoribosyl pyrophosphate (PRPP) – a key building block for DNA, RNA and energy-rich molecules.

“Within this complex, PRPS2 helps stabilize its partner, PRPS1, to maintain enzyme activity. Since lung tissues express low levels of other PRPS complex-stabilizing proteins (PRPSAP1 and PRPSAP2), disrupting PRPS2 could destabilize the complex, causing PRPS1 to become less active,” he explained. “This reduces enzyme activity, limits nucleotide production, impairs cellular metabolism, and ultimately slows or stops tumor growth.”

This research has the potential to alter caner treatment by shifting from targeting cancer-causing genes to disrupting the metabolic weaknesses that cancer cells rely on. If successful, this strategy could lead to more effective therapies for KRAS-mutant lung cancer and other cancers with similar metabolic dependencies.

“My research focuses on understanding how cancer cells rewire fundamental metabolic pathways to fuel tumor growth, with the goal of uncovering vulnerabilities that can serve as potential therapeutic targets,” Karki shared. “This is especially important for cancers like KRAS-mutant lung cancer, which are often resistant to current treatments. By studying the metabolic dependencies of these hard-to-treat cancers, we aim to identify novel targets that could lead to more effective therapies. I approach this challenge through the lens of structural biology and biochemistry, which provides detailed insights into the molecular mechanisms of enzymes and enzyme complexes driving cancer metabolism. This knowledge is crucial for designing therapies that selectively disrupt cancer cell survival while sparing normal cells.”

As this award provides both critical funding and validation of his innovative approach to cancer treatment, this marks a significant milestone in Karki’s research and career. Beyond advancing his research, this recognition fuels his commitment to developing translational discoveries that could lead to improved treatments for hard-to-treat cancers.

“Receiving this award is not only an honor but a pivotal opportunity for my research and career development,” he shared. “This award not only provides critical funding to advance my project on targeting the PRPS complex in KRAS-mutant lung cancer but also reinforces the significance of exploring novel therapeutic strategies in cancer metabolism. Beyond the research itself, this recognition motivates me to continue pursuing innovative approaches in cancer biology and strengthens my commitment to contributing to translational discoveries that could ultimately benefit patients. It’s incredibly encouraging to have the support of the Cancer Center, and I’m excited about the potential impact this work could have in shaping new therapeutic avenues for hard-to-treat cancers.”

Overcoming the Blood-Brain Barrier: Enhancing Therapeutic Delivery to Glioblastoma via Novel Methods

Sirjana Pun Trainee Associate Member University of Cincinnati Cancer Center Mentor: Riccardo Barrile, PhD

Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer, with a median survival rate of just 20 months despite current interventions. A major challenge in treating GBM is the blood-brain barrier (BBB), which limits drug delivery.

“My work focuses on creating advanced lab models to test new treatments for the study of glioblastoma multiforme (GBM),” Pun shared. “These models help evaluate the safety and efficacy of potential drugs before they are used in patients. Since glioblastoma can vary from person to person – and even between different tumors in the same patient – these models are especially valuable for understanding individual disease profiles. This approach can help tailor treatment plans to meet each patient’s unique needs.”

Through her Overcoming the Blood-Brain Barrier: Enhancing Therapeutic Delivery to Glioblastoma via Novel Methods project, Pun and her team are exploring two promising methods to enhance drug penetration – focused ultrasound (FUS) and adeno-associated virus (AAV) vectors. Focused ultrasound (FUS), combined with microbubbles, temporarily opens the blood-brain barrier to allow drugs like nab-paclitaxel – a nanoparticle chemotherapy – to reach brain tissue. Additionally, the study will also test AAV-based gene therapy using AAV9 to deliver a silencing gene targeting CD133 – a cell marker linked to chemotherapy resistance.

“Currently, I am focused on developing advanced, high-throughput 3D models, which means that they can be used to test multiple drug candidates across different patient samples at the same time, helping speed up research,” she explained. “These models are also customizable, allowing them to be adapted for different tissues and organs. Compared to animal testing, this approach is faster, more cost-effective, and provides a more accurate way to evaluate potential treatments before they move to clinical trials.”

New drugs are typically tested in animals first, but since animal biology differs from humans, many drugs that seem effective in animals fail in human trials—over 90% of them, in fact. To address this, Pun and her team are using a lab-grown system made from human cells and materials, allowing for more accurate predictions of how drugs will affect people.

“By creating more physiologically relevant in vitro models, my research aims to improve the translational value of preclinical drug testing, reducing reliance on animal models and accelerating the path to clinical application,” Pun explained. “My models account for glioblastoma’s patient-to-patient and intra-tumor variability, making them valuable for studying personalized treatment responses and guiding precision medicine strategies.”

For Pun, the Trainee Associate Membership (TAM) Program and the TAM Pilot Project Awards represent more than just funding – they symbolize a vital opportunity for collaboration, inspiration and growth as a researcher. This recognition has connected her with leading experts at the Cancer Center, fostering interdisciplinary partnerships that enhance her work.

“My Trainee Associate Membership with the Cancer Center has been instrumental in advancing my research,” she shared. “It has given me the opportunity to share my work with colleagues and mentors, gaining valuable insights while also learning about their research. This membership has helped bring together diverse expertise, allowing for innovative problem-solving and accelerating progress in glioblastoma research.”

“Furthermore, the TAM Pilot Project Awards hold a special place in my heart,” Pun said. “Receiving this award has granted me invaluable access to expertise and interdisciplinary collaborations at the Cancer Center. I am constantly inspired by the innovative and impactful work of the faculty and clinicians here, and I am deeply grateful to the entire community for this recognition. Beyond financial support, this award serves as a powerful source of motivation, driving me to continue advancing novel therapeutic developments for glioblastoma using cutting-edge preclinical models.”

Travel Awardees

Characterization of E1 Ligase Dependencies in a Mutant-UBA1 Human Cell Model Reveals UBA6 as a Novel Therapeutic Target in VEXAS Syndrome

Courtnee Clough, PhD Trainee Associate Member University of Cincinnati Cancer Center Mentor: Daniel Starczynowski, PhD

VEXAS (Vacuoles, E1-ligase, X-linked, Autoinflammatory, Somatic) syndrome is a newly defined clonal hematopoietic malignancy that often co-occurs with myelodysplastic syndromes (MDS). It is marked by hyperinflammation, bone marrow failure and high rates of mortality. The disease is caused by mutations at methionine 41 (M41) in UBA1, leading to a defective UBA1c protein. However, how this mutation alters protein regulation and contributes to disease progression remains unclear.

“To study VEXAS, we used CRISPR/Cas9 to create human cell models with either normal (WT) or mutant (MUT) UBA1,” Dr. Clough explained. “MUT cells showed key VEXAS features, including abnormal protein buildup and increased vacuolization. We investigated how these mutations affect protein tagging (ubiquitination) by reducing levels of UBA1 or its related enzyme, UBA6. While knocking down UBA1 or UBA6 alone did not drastically change global ubiquitination, it impaired cell growth. Interestingly, mutant UBA1 cells became more dependent on UBA6 for survival.”

Dr. Clough’s Characterization of E1 Ligase Dependencies in a Mutant-UBA1 Human Cell Model Reveals UBA6 as a Novel Therapeutic Target in VEXAS Syndrome study has identified a key ubiquitin enzyme – UBA6 – as a potential unexplored therapeutic target in VEXAS syndrome.

“To explore potential treatments, we tested inhibitors targeting UBA1 (TAK-243) and UBA6 (phytic acid),” she said. “While TAK-243 reduced growth in both normal and mutant cells, UBA6 inhibition with phytic acid selectively impaired the survival of mutant UBA1 cells. These results suggest that UBA6 is essential for mutant UBA1 cells, highlighting it as a promising therapeutic target for VEXAS syndrome. Since ubiquitin is dysregulated in many cancers, we hope to expand our work in VEXAS syndrome to blood cancers more broadly.”

Attending and presenting research at prestigious conferences is a crucial step in advancing scientific discovery and fostering collaboration. For Dr. Clough, receiving this award has been instrumental in expanding the reach of her work and engaging with experts in the field.

“This award provided me the opportunity to not only attend but also present my work at the 2024 American Society of Hematology Annual Meeting,” Dr. Clough shared. “Furthermore, through the TAM Program, I have been given the ability to share my work within the Cancer Center community and the broader international community, which has been pivotal in advancing this project.”

Combining Plk1 Inhibition and Radiation to Target Head and Neck Cancer

Julianna Korns, PhD Trainee Associate Member University of Cincinnati Cancer Center Mentor: Vinita Takiar, MD, PhD

Head and neck cancer is the sixth most common cancer worldwide, and radiation is a cornerstone treatment for these patients, yet many, particularly those with HPV-negative tumors, remain resistant to current therapies. Dr. Korns’ and her team have identified a promising new approach: combining radiation with the PLK1 inhibitor onvansertib.

“Head and neck cancer is an aggressive disease, and there hasn’t been much progress made in advancing standard of care therapies to prolong survival and improve side effects,” explained Dr. Korns. “Our work has identified a novel drug – onvansertib – that can be combined with radiation to improve therapy effectiveness in a population of patients with head and neck cancer who are typically more resistant to current therapies.”

“Our research shows that high levels of polo-like kinase 1 (Plk1) are linked to poorer survival in head and neck cancer patients,” she said. “In lab and animal models, combining the Plk1 inhibitor onvansertib with radiation slowed HPV- HNC tumor growth. Since onvansertib is already FDA-approved and in clinical trials for other cancers, this combination could offer a new and effective treatment option to improve survival for HPV- HNC patients.”

This novel combination has shown potential to improve treatment efficacy, offering new hope to patients who previously had limited options. Additionally, Dr. Korns and her colleagues have identified MMP10 as a downstream target of PLK1, which could be manipulated to further improve patient outcomes.

Conferences provide a platform for researchers to share insights, refine ideas, and build meaningful collaborations. With the support of this award, Dr. Korns has been able to extend the reach of her research and engage with experts in her field.

“Receiving this award allowed me to attend the American Society for Radiation Oncology Conference, which gave me the opportunity to expand my network and meet other researchers with like-minded interests,” Dr. Korns shared. “None of this – the networking, the award – would have been possible without the Trainee Associate Membership Program. The TAM Program has provided access to various funds that enhance my research and share it with the broader community outside of the Cancer Center and the University of Cincinnati.”

Paper of the Year Co-Awardees

Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma

Megan Bischoff, PhD Trainee Associate Member University of Cincinnati Cancer Center

Juechen Yang Trainee Associate Member University of Cincinnati Cancer Center

Dina Secic Trainee Associate Member University of Cincinnati Cancer Center

Mentors: Maria Czyzyk-Krzeska, MD, PhD and Jarek Meller, PhD

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, becomes more copper enriched as it advances, increasing the likelihood of recurrence. Copper fuels cytochrome c oxidase, an enzyme that is vital for energy production and metabolic reprogramming in cancer cells.

“In this publication, we reveal how copper accumulates in progressing clear cell renal cell carcinoma (ccRCC), reshaping several aspects of cellular metabolism, including most importantly mitochondrial respiration,” explained Dr. Bischoff. “This metabolic shift must be carefully balanced with the production of glutathione – a protective molecule that shields cells from damage caused by reactive oxygen byproducts. By analyzing patient tumors at single-cell and spatial levels, we identify distinct cancer cell populations and demonstrate that the activation of copper, metabolic, and protective pathways is linked to tumor regions showing signs of rapid growth. These findings suggest that targeting these pathways could expose new therapeutic vulnerabilities in ccRCC.”

Building on their work, Dr. Bischoff and Secic continue to investigate how copper alters cell behavior in clear cell renal cell carcinoma (ccRCC) and how it is allocated within tumors. These studies will provide further insights into the ways copper contributes to cancer progression and the fundamental processes controlling its regulation in cells.

Yang is a computational biologist studying the diversity of ccRCC by combining different types of biological data, which helps create models that improve early cancer detection and identify high-risk patients. Using advanced computational techniques, he analyzes cancer at the genetic and cellular levels. By studying single-cell and spatial transcriptomics data, he explores how tumors grow and interact with their environment. His research connects computational biology with clinical oncology, using machine learning to enhance cancer detection, predict patient outcomes, and develop personalized treatments.

“Machine learning models are useful tools in cancer research,” explained Yang. “They can help identify high-risk genetic profiles in cancer patients. Integrating spatial transcriptomics with deep learning models can provide deeper insights into tumor microenvironments. Developing scalable computational pipelines is crucial for high-throughput cancer genomics research.”

“We hope our collective work will help identify new therapeutic targets and improve precision medicine approaches for cancer treatment,” the authors said. “Cancer biology is highly complex and understanding its genetic and cellular landscape is key to developing effective treatments. Understanding what drives cancer development and progression is fundamental to developing targeted therapies to improve patient outcomes.”

Reflecting on the achievement of receiving the Paper of the Year Award for this work, Dr. Bischoff expressed her gratitude, emphasizing the critical role teamwork played in their groundbreaking research.

“We are incredibly honored to receive the Paper of the Year Award,” she expressed. “We are part of a highly collaborative group with expertise spanning molecular and cellular biology, bioinformatics, metal biology, metabolism and beyond. To us, this award represents the power of teamwork in advancing scientific discoveries. It highlights how collaborative research can deepen our understanding of the fundamental processes underlying disease, ultimately leading to insights that drive improvements in patient care.”

Dr. Bischoff also took a moment to recognize the unique opportunities her membership with the Cancer Center provides for both professional and personal development, reflecting how it has facilitated her growth as a researcher and deepened her understanding of the intersection between clinical practice and basic research.

“Being a member of the Cancer Center community connects us to experts in the field and allows us opportunities as basic researchers to learn more about the current practices, gaps and needs in the clinic,” she shared. “Through the Cancer Center, we also have access to training, support and resources that allow us to further both our research and personal growth as developing researchers.”