The University of Cincinnati Cancer Center’s Office of Cancer Research Training and Education Coordination (CRTEC) is proud to announce the selection of the 2025 Dr. Peter Stambrook pilot grant awardees, supported by the American Cancer Society Institutional Research Grant Program. Through the Institutional Research Grant Program, the American Cancer Society funds major cancer centers throughout the country to establish a pilot grant program specifically dedicated to early-stage investigators working in cancer-related fields. With matching funding provided by the Cancer Center, each funded investigator will receive $80,000 in research support.

2025 Dr. Peter Stambrook Pilot Awardees

Ferroptosis Suppression Drives Therapy Resistance in Mutant KRAS Lung Cancer

Cristina Andreani, PhD Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center Research Assistant Professor, Department of Internal Medicine University of Cincinnati College of Medicine

“Lung cancer with KRAS mutations tends to be aggressive and challenging to treat,” Cristina Andreani, PhD, a basic scientist at the Cancer Center shared. “In our research, we identified a promising strategy – inducing ferroptosis, a form of cancer cell death driven by iron and oxidative stress. We discovered that inhibiting, or blocking, the enzyme FASN can trigger ferroptosis in lung cancer cells, leading to a phase II clinical trial for patients with KRAS-mutant lung cancer.”

KRAS mutations are genetic alterations in the Kirsten rat sarcoma viral oncogene (KRAS) gene that contribute to lung cancer development, occurring in about 30% of cases. These mutations drive uncontrolled cell growth and division by activating a signaling pathway that promotes cancer progression and resistance to treatment. As a result, KRAS-mutated lung cancer is often more aggressive and linked to a poorer prognosis. Researchers, like Dr. Andreani and her team, are working to resolve this.

“This study investigates the mechanisms behind treatment resistance and how to overcome it, offering insights for improved therapies,” she explained. “We identified a protein, KDM6B, that supports cancer cell survival by switching on alternative genes that prevent ferroptosis. Through experiments in lab models and mice, we aim to uncover new drug targets and deepen our understanding of how ferroptosis is regulated in therapy-resistant cancer.”

KDM6B plays a key role in helping cancer cells avoid ferroptosis and resist treatment. By blocking KDM6B, the team hopes to increase the susceptibility of lung cancer cells to ferroptosis-driven therapies, enhancing their effectiveness.

“This research has the potential to reshape how we approach lung cancer treatment,” Andreani said. “Many existing therapies, including those targeting KRAS mutations, eventually fail due to this acquired resistance. However, by targeting specific ferroptosis weaknesses, we can create improved combination therapies that reduce treatment failure and enhance patient outcomes. Furthermore, because ferroptosis is a critical factor in various cancer treatments, the findings from this study could have broader applications beyond FASN and lung cancer, advancing cancer research as a whole.”

Dr. Andreani's work focuses on overcoming a major obstacle in lung cancer treatment – therapy resistance using ferroptosis-based approaches. Moving this research forward requires substantial support, and with the Dr. Peter Stambrook pilot grant, she now has the resources to expand her studies. Reflecting on this milestone, she shared her excitement about the impact this funding will have on her research and its potential to improve treatment options for patients.

“Receiving this award is an incredible opportunity to advance my research on therapy resistance in lung cancer,” she shared. “It provides the support needed to establish my independent research program and develop new therapeutic strategies for patients with KRAS-mutant lung cancer. This funding allows me to generate key preliminary data that will support future grant applications and, ultimately, contribute to the development of more effective treatment combinations.”

Dr. Andreani also emphasized the significant impact of her Cancer Center membership on her research, noting that it has been instrumental in her professional development by offering mentorship, access to research resources and valuable networking opportunities.

“My Cancer Center membership has been incredibly beneficial to my career,” she said. “It has provided mentorship, access to research resources and networking opportunities that have helped refine my research approach and strengthen my grant applications. Through this program, I have been able to collaborate with other experts in the field and gain valuable insights that have shaped the direction of my work.”

Targeting Glioblastoma Resistance: An Organ-on-Chip Model Combined with Focused Ultrasound-Enhanced Drug Delivery

Riccardo Barrile, PhD Member, Experimental Therapeutics Research Program University of Cincinnati Cancer Center Assistant Professor, Department of Biomedical Engineering University of Cincinnati College of Engineering & Applied Science

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, with current treatment options – surgery, radiation and temozolomide chemotherapy – offering limited long-term success due to drug-resistant tumor cells and the protective role of the blood-brain barrier (BBB). Emerging therapies face challenges in penetrating the BBB and addressing patient-specific drug resistance mechanisms.

“To address these challenges, we are creating a ‘brain-tumor-on-a-chip,’ a 3D model that mimics the tumor environment using patient-derived cells, combined with focused ultrasound (FUS) to enhance drug delivery,” shared Riccardo Barrile, PhD, a clinical researcher at the Cancer Center. “This innovative platform allows us to study drug resistance and test personalized treatments in a more realistic setting, offering a new pathway to overcome the limitations of current therapies.”

Dr. Barrile and his team have developed a groundbreaking “brain-tumor-on-a-chip” model that replicates key anatomical and molecular aspects of an actual tumor, including hypoxic and perivascular niches that drive drug resistance. By integrating focused ultrasound with microbubbles, the blood-brain barrier can be temporarily opened, allowing therapeutic drugs – once considered incapable of crossing this barrier – to reach the tumor site.

“This research not only deepens our understanding of glioblastoma biology but also provides a valuable translational tool for testing and optimizing personalized therapies in the clinical setting,” Dr. Barrile said. “This award provides critical support to refine our model, optimize our techniques and accelerate the development of these groundbreaking treatments, bringing us closer to delivering effective, personalized therapies for those battling this devastating disease.”

Dr. Barrile’s work seeks to advance the understanding of glioblastoma (GBM) and improve drug delivery, with the potential to reshape treatment approaches for GBM and other cancers, ultimately enhancing patient survival and quality of life. He took a moment to express his deep gratitude for the Dr. Peter Stambrook pilot grant, viewing it as both a major career milestone and a meaningful recognition of his dedication. Additionally, he acknowledges the grant as a reflection of the collaborative, multidisciplinary efforts that have been instrumental in shaping his research.

“For me, this award is a recognition of the collaborative efforts that have shaped my career at the University of Cincinnati, particularly my close partnership with world-leading experts like Prof. Howarth in the field of FUS,” he shared. “Our established work together has laid the foundation for this proposal, and this award will enable us to build on those efforts, enhancing our models and exploring new ways to enhance drug delivery and therapeutic efficacy. It also reflects the importance of teamwork in driving scientific discovery, as our multidisciplinary approach brings together diverse expertise to address pressing challenges in cancer research.”

Dr. Barrile also credited his Cancer Center membership as a vital catalyst for his research, providing invaluable support despite having a background not solely in cancer biology. Reflecting on the impact of this membership, Dr. Barrile shared how it has strengthened his team’s ability to develop innovative approaches to tackling the challenges of brain tumors.

“My Cancer Center membership has been a tremendous asset to my research,” he said. “Even though my background is not purely in cancer biology, being a part of this vibrant community has facilitated the exchange of ideas and fostered collaborations with experts across disciplines. Regular meetings and interactions with the scientific community at the Cancer Center have broadened my perspective and accelerated my scientific growth. Additionally, this membership has granted my team access to state-of-the-art facilities and resources, which have been critical in achieving rapid and impactful results. The integration of these advanced tools into our work has allowed us to push the boundaries of our research, helping us develop innovative approaches to address the challenges of brain tumors.”

ACSL3: A Promising Target in Lipid Metabolism for Mutant KRAS Lung Cancer Therapy

Caterina Bartolacci, PhD Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center Research Assistant Professor, Department of Internal Medicine University of Cincinnati College of Medicine

Lung cancer is the leading cause of cancer deaths in the United States and worldwide. There are two main categories of lung cancer: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer (NSCLC) is the most common form of the disease, accounting for about 80% of diagnosed cases.

Approximately 30% of non-small cell lung cancer patients have mutations in the KRAS gene, and very few of these patients benefit from treatments like immunotherapy or drugs that specifically target KRAS. Identifying specific weaknesses in the cancer cells could help develop better treatments, and Caterina Bartolacci, PhD, a basic science researcher at the Cancer Center, is working to achieve this.

“I found that KRAS mutations increase the production of ‘cancer-friendly’ fatty acids, which help the cells reduce damage from harmful molecules called reactive oxygen species (ROS),” she explained. “Thus, limiting the availability of these ‘cancer-friendly’ fatty acid triggers a type of cell death called ferroptosis, which is linked to the buildup of ‘cancer-poisonous’ fatty acids.”

Fatty acids are the building blocks of lipids, and fatty acid synthesis, or lipogenesis, is a metabolic process where the body converts excess glucose and other nutrients into fatty acids for energy storage and other cellular functions. Dr. Bartolacci’s research primarily focuses on lung cancer and aims to shed light on the still poorly understood role that lipids play in cancer cells, beyond their functions in providing energy and signaling molecules.

“The goal is to explore how lipids can be leveraged to induce cancer cell death,” she explained. “The impact of this research lies in uncovering novel, unexplored metabolic dependencies of cancer cells, particularly expanding the role of lipids beyond their well-known functions in energy production and signaling. By gaining a deeper understanding of these metabolic pathways, we could identify new therapeutic targets, revealing potential vulnerabilities for more effective treatments.”

To achieve this, though, Dr. Bartolacci and her team must develop innovative, cutting-edge mass spectrometry-based techniques to study lipids in greater detail.

“This award will significantly support the cost of this research, providing essential resources for furthering my work on lipid metabolism in cancer cells,” she shared. “It will allow me to continue developing the cutting-edge techniques and experimental tools needed to deepen our understanding of metabolic pathways and identify new therapeutic targets. Ultimately, this funding will be instrumental in translating my research into meaningful discoveries that could lead to more effective cancer treatments.”

Dr. Bartolacci also reflected on the significant impact of her membership with the Cancer Center, highlighting how it has been essential in advancing her research. Through her interactions with fellow researchers, she has gained fresh perspectives that have propelled her work forward.

“Being a Cancer Center member has played a crucial role in advancing my research by offering valuable feedback and guidance from a diverse group of experts,” she said. “Being able to interact with fellow researchers and senior faculty has allowed me to refine my research approach and provided new perspectives on my work. Additionally, this membership has given me access to resources and networking opportunities, which have been crucial for developing my research and moving forward with my projects.”

Determining the Role of MRAS in Modulating Primary and Acquired Resistance to KRAS Inhibition

Andrew Waters, PhD Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center Assistant Professor, Department of Surgery University of Cincinnati College of Medicine

Kirsten rat sarcoma viral oncogene (KRAS) is a gene that plays a role in cell growth and division. KRAS encodes a protein that acts as a switch, turning on and off signaling pathways that control cell growth, differentiation and survival. However, when KRAS becomes mutated, it essentially is stuck in the “on” position, causing uncontrolled cell growth, which can lead to aggressive and deadly cancer.

Occurring in over 90% of pancreatic cancers, KRAS mutations drive tumor growth. Unfortunately, pancreatic cancer has a 5-year survival rate of 13%, and for a long time, KRAS was considered untreatable. Recent breakthroughs, however, have led to drugs targeting mutant KRAS, which are now in clinical trials. While early results are promising, most patients relapse due to resistance to treatment.

“We believe that MRAS, a close relative of KRAS, may help tumors grow and drive resistance to anti-KRAS drugs,” explained Andrew Waters, PhD, a basic science researcher at the Cancer Center. “The goal of this project is to understand how MRAS contributes to KRAS drug resistance and identify new treatment strategies to improve the efficacy of anti-KRAS therapies.”

The muscle RAS oncogene homolog (MRAS) is a gene that encodes a membrane-bound, small GTPase protein called Ras-related protein M-Ras, which functions as a signal transducer in the Ras-MAPK pathway, regulating cell proliferation and survival. MRAS and KRAS are both small GTPases belonging to the RAS family, involved in cell signaling pathways. While MRAS is structurally similar to KRAS and is involved in signaling pathways that regulate cell growth, differentiation and survival like KRAS, MRAS binds directly to SHOC2, whereas other RAS proteins, including KRAS, do not.

“We hypothesize that increased MRAS activity causes primary resistance to KRAS by boosting ERK MAPK signaling and contributes to acquired resistance by increasing cell flexibility,” Waters explained. “We will test this using cell culture, animal models and patient samples. The results will provide key data for a future ACS RSG grant and could lead to new KRAS treatment combinations for pancreatic cancer patients.”

Reflecting on his journey with the American Cancer Society, Dr. Waters shared how meaningful it is to have the ACS invest in his current research.

“My first successful grant was actually from the American Cancer Society as a postdoc,” he shared. “Since then, I have participated in the American Cancer Society Relay for Life as an advocate, supporter and researcher, and seeing things come full circle, where the American Cancer Society invests in our research, is truly impactful. Furthermore, this award will allow us to generate data that can be a springboard towards important advancements in the field.”

About the ACS IRG

The American Cancer Society awards Institutional Research Grants to academic and nonprofit organizations that have a track record of outstanding cancer research and a pool of experienced researchers who can mentor junior faculty. The purpose is to support early-stage faculty investigators in initiating cancer research projects so they can obtain preliminary results that will enable them to compete successfully for national research grants.

“The American Cancer Society is committed to investing in the careers of the best and the brightest early-stage investigators who can bring innovative ideas to the forefront. By supporting institutions with seed funding for newly independent investigators to initiate cancer research projects, these institutions can utilize the preliminary results to successfully compete for national research grants,” said Natasha Coleman, MPH, vice president of community impact, American Cancer Society. “We are confident that this institutional research grant, under the mentorship of our long-time collaborators and established leaders at the University of Cincinnati Cancer Center, will launch new researchers who can further our understanding of cancer and its treatment.”

Cancer Center member David Plas, PhD, is the primary investigator for the grant, with members Maria Czyzyk-Krzeska, MD, PhD, and Kathryn Wikenheiser-Brokamp, MD, PhD, serving as co-principal investigators.