DNA Repair Research for Cancer Therapy at the University of Arkansas for Medical Sciences
Wolfe Lab | Translational Radiation Oncology
The Wolfe Lab is an interdisciplinary research lab that spans the interface between DNA repair and radiation therapy in deadly cancers. The lab studies aspects of oncogenic DNA repair regulation, homologous recombination dynamics, and radiation mouse models of human cancer.
Research Program
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The Wolfe lab investigates DNA repair pathways leading to treatment resistance to radiation therapy, novel DNA damage radiation biomarkers, and the development of novel DNA repair targets to improve responses to radiation therapy. We are interested in understanding the molecular drives of radiation resistance.
Our main disease of focus is pancreatic cancer. We utilize genetic and proteomic approaches to address the fundamental mechanisms of genetic alterations in cancer cells, resulting in heightened DNA repair leading to radiation resistance. We have developed relevant in vitro and in vivo models of human cancer that mimic the disease phenotype in patients.
The projects that we currently are working on in the lab are:
1. Role of DNA repair proteins in radiation resistance in KRAS mutant pancreatic cancer. DNA repair is critically important for maintaining the radioresistant phenotype of KRAS mutant pancreatic cancer. We are studying ways to target upregulated DNA repair pathways that
can enhance tumor control and clinical outcomes through “biological dose escalation” to the tumor while sparing the surrounding critical structures.
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2. Translational model of radiation therapy in pancreatic cancer. We have developed a clinically relevant pancreatic preclinical model to understand better the role of DNA repair on therapeutic response. We use a Small Animal Radiation Research Platform combined with the high field MRI available at UAMS. We are testing novel radiosensitizers that could be moved into Phase I clinical trials using this model.
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3. DNA Damage biomarkers for treatment guidance. We utilize the quantitative immunohistochemistry for DNA repair proteins on pre-treatment biopsy samples to correlate clinical outcomes following radiation. We can discover novel DNA damage biomarkers to personalize treatments for our cancer patients.
Key Publications
Clinical Cancer Research (Journal)
Discovery of the inhibitor of DNA binding 1 as a novel marker for radioresistance in pancreatic cancer using genome-wide RNA-seq
Clinical Cancer Research
BRAF mutation drives radiation resistance in Thyroid Cancer through upregulation of DNA repair pathways .Read our publication here.
Breast Cancer Research and Treatment
Simvastatin inhibits in vitro endpoints associated with metastasis through a FOXO3a mechanism and reduced metastasis formation in vivo.
Clinical Cancer Research
Altered scheduling regimen increases efficacy of the chemotherapy in resistant pancreatic cancer.
Our Publication Library
Our Team
Adam Wolfe MD, Ph.D.
Principal Investigator
Dr. Wolfe is a physician-scientist in Radiation Oncology at the University of Arkansas for Medical Sciences (UAMS). He is an assistant professor as of 2021. He is passionate about translational oncology research to provide better treatment outcomes for our patients. In the clinic, he treats patients with gastrointestinal cancers. In the lab, he researches new strategies to improve radiation therapy.
Saaimatul Huq Ph.D.
Post Doctoral Fellow, Department of Radiation Oncology
Saaima joined the lab in October 2023. She holds a PhD from Saitama University, Japan. Before joining the lab, she completed her postdoctoral research at the Toronto Metropolitan University, Canada. There, she specialized in lysosomal remodeling in mouse macrophages and developed a machine-learning model for lysosomal tubulation. She also contributed to the detection of COVID-19, HIV, and bacteria using ELiMSA. Currently, Saaima is focusing on uncovering the molecular drivers of radiation resistance in KRAS mutant pancreatic cancer and discovering DNA repair targets for enhanced treatment strategies.
Lokesh Akana M.S.
PhD. candidate, Department of Biochemistry & Molecular Biology (GPIBS)
Lokesh joined our laboratory in January 2023. His academic journey commenced with a strong focus on cancer research, culminating in a Master’s degree in Biological Sciences from Arkansas State University, Jonesboro. Eager to deepen his understanding of the molecular mechanisms underlying disease progression, Lokesh seamlessly transitioned into radiation oncology at UAMS, where he is thriving as a promising young researcher. In Dr. Wolfe’s lab, his research focuses on studying the role of methyl transferase SETD2 in mediating signals of KRAS mutation-induced radiation resistance in colorectal cancers. This research has the potential to significantly advance our understanding of cancer biology and contribute to the development of novel therapeutic strategies.
Henrique Favorin Rodrigues B.S.
Research Assistant, Department of Radiation Oncology
Henrique joined the laboratory in April 2022. He has a MeD in Chemistry from the Federal University of São Carlos, Brazil. He has over a decade of experience in research.
Former Members
Oscar Zuniga
Laboratory Technician, Department of Radiation Oncology
Oscar joined the laboratory in August 2021. He is currently a student at the University of Arkansas in Little Rock. His long-term goal is to attend medical school.
Summer Students
Summer 2023:
Alexander Browning - BA Candidate, Ouachita Baptist University
Jessica Pittman - BA Candidate, University of Arkansas at Little Rock
Summer 2022:
Robin Eluvathingal - BA Candidate, University of Arkansas at Fayetteville
Stetson VanMatre - BS Candidate, University of Central Arkansas
News
Stay Informed About Wolfe Lab | Radiation Oncology Research
Dr. Wolfe receive ACS grant!
Dr. Wolfe receive a $583,200 grant from the American Cancer Society (ACS) to study radiation resistance in pancreatic cancer.
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Dr. Wolfe is awarded a KL2 award!
Dr. Wolfe was awarded a KL2 Mentored Research Career Development Scholar Award from the UAMS Translational Research Institute. This award will fund the research in Dr. Wolfe's lab for 2 years.
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Wolfe lab awarded Team Science Award!
The Winthrop P. Rockefeller Cancer Institute Team Science Award supports new cancer-focused research between Cancer Institute members.