Megan Reann Reed, PhD

Research Program: Cancer Biology Faculty Rank: Postdoctoral Fellow Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Biochemistry & Molecular Biology

Cancer Research Interest

• Disease Site Focus: Cutaneous/Melanoma, Brain, Gynecology
• Research Focus Area: Treatment
• Research Keywords: functional precision medicine, cancer, immunology
• Type of Research: Clinical
• Research Interest Statement: High grade brain tumors and brain metastases are difficult to treat for many reasons; they generally have an abysmal response to standard-of-care chemotherapeutics, responders have high rates of recurrence, and survival is greatly reduced. The main factor contributing to this poor response and eventual resistance is tumor heterogeneity. Organoid model systems eliminate the lack of heterogeneity found in two-dimensional culture, quickly and accurately recapitulating the patient-specific tumor microenvironment. Our plan is to combine comparative transcriptomics with personalized PDO screening, making UAMS uniquely capable of generating personalized treatment strategies. Traditional precision medicine platforms use genomics-based data to identify actionable mutations, but do not test potential therapies on PDOs. Our innovative paradigm will use a combination of comparative transcriptomics/proteomics and functional validation of target compounds to establish bespoke therapeutic treatments and improve patient outcomes. Our comparative transcriptomics platform analyzes patient gene expression patterns relative to a compendium of other solid tumors to identify upregulated pathways which are linked to targetable endpoints (i.e. FDA approved drugs). We will expand this paradigm to include unbiased proteomics given proteins are the primary targets of cancer-based therapies. We also hope to further expand upon this pipeline to include screening for PDO immune response. Our functional validation step using PDO models can generate drug sensitivity data in as little as a week and as such is more cost and time effective than traditional in vivo models. We have used this platform to generate preliminary data and would like to continue to build upon these findings to strengthen the case for functional precision medicine.

Contact Information

• Email Address: mrreed@uams.edu
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Publications

• Delgado M, Rainwater RR, Heflin B, [et al., including Reed MR]. Primary acute lymphoblastic leukemia cells are susceptible to microtubule depolymerization in G1 and M phases through distinct cell death pathways. The Journal of biological chemistry. 2022 298(6):101939. PMID: 35436470.
• Reed MR, Lyle AG, De Loose A, [et al.]. A Functional Precision Medicine Pipeline Combines Comparative Transcriptomics and Tumor Organoid Modeling to Identify Bespoke Treatment Strategies for Glioblastoma. Cells. 2021 10(12). PMID: 34943910. PMCID: PMC8699481.
• Urbaniak A, Reed MR, Fil D, [et al.]. Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021 141:111815. PMID: 34130123.
• Reed MR, Maddukuri L, Ketkar A, [et al.]. Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells. NAR cancer. 2021 3(2):zcab014. PMID: 33870196. PMCID: PMC8034706.
• Ketkar A, Smith L, Johnson C, [et al., including Reed MR]. Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs. Nucleic acids research. 2021 49(4):2065-2084. PMID: 33555350.
• West KL, Kelliher JL, Xu Z, [et al., including Reed MR]. LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic acids research. 2019 47(12):6236-6249. PMID: 30982887. PMCID: PMC6614850.
• Ketkar A, Maddukuri L, Penthala NR, [et al., including Reed MR]. Inhibition of Human DNA Polymerases Eta and Kappa by Indole-Derived Molecules Occurs through Distinct Mechanisms. ACS chemical biology. 2019 14(6):1337-1351. PMID: 31082191. PMCID: PMC7357868.
• Zafar MK, Maddukuri L, Ketkar A, [et al., including Reed MR]. A Small-Molecule Inhibitor of Human DNA Polymerase ? Potentiates the Effects of Cisplatin in Tumor Cells. Biochemistry. 2018 57(7):1262-1273. PMID: 29345908.
• Byrd AK, Zybailov BL, Maddukuri L, [et al., including Reed MR]. Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress. The Journal of biological chemistry. 2016 291(34):18041-57. PMID: 27369081. PMCID: PMC5016190.
• Bostian AC, Maddukuri L, Reed MR, [et al.]. Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells. Chemical research in toxicology. 2016 29(1):101-8. PMID: 26651356. PMCID: PMC4718841.