Ryan M Allen, PhD

Research Program: Cancer Biology Faculty Rank: Assistant Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Physiology & Cell Biology

Cancer Research Interest

• Disease Site Focus: Multiple Myeloma
• Research Focus Area: Treatment, Prevention, Informatics
• Type of Research: Basic
• Research Keywords: multiple myeloma, cholesterol
• Research Interest Statement: Multiple myeloma (MM) remains an incurable malignancy in most patients, who will eventually relapse and become refractory to existing therapies. There is thus a critical need for therapeutic innovations that maintain remission and preserve patient quality of life. As a cell biologist broadly trained in sterol and lipid metabolism, I became intrigued by the unique localization of MM tumors within the hypoxic tumor microenvironment (TME) of the bone marrow. Cell proliferation is limited by the availability of cholesterol, the de novo synthesis of which is energy- and oxygen-intensive. Moreover, hematopoietic cells in the bone marrow maintain high demand for raw materials necessary for growth. To overcome limitations in de novo cholesterol synthesis, all cells can rapidly increase cellular sterol levels and stimulate membrane biosynthesis through uptake of cholesterol-rich low-density lipoprotein (LDL). We speculate that heightened demand for sterols in the MM-TME explains the common observation of low plasma cholesterol levels reported in MM patients. Most interestingly, though, epidemiological studies have found that statins, a common class of LDL-lowering drugs, increases progression free survival in MM, perhaps through depriving malignant cells of sterols necessary for tumor growth. One objective of my cancer research program is to identify new complimentary approaches to treat MM based on manipulating sterol metabolism and membrane biosynthesis pathways, in MM cells, but also at the organismal level. Separately, we have published that LDL also transport small RNAs that promote macrophage polarization by activating an endosomal sensor of RNA, toll-like receptor 8 (TLR8). New data from our laboratory support that TLR8 activity contributes to defective metabolic reprogramming in macrophages consistent with myeloid-derived suppressor cells. Given that immunosuppression is common in advanced and relapsing MM, our other primary objective is to determine whether TLR8 is a viable target for restoring immune function in MM patients. Collectively, we use an innovative combination of in vitro, ex vivo, and in vivo mouse models of MM, together with state-of-the-art bioinformatic, imaging and single cell immune profiling approaches to test new diagnostic and therapeutic approaches for MM.

Contact Information

• Email Address: RMALLEN2@UAMS.EDU
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Recent Publications

• Hoogenboezem EN, Patel SS, Lo JH, [et al., including Allen RM]. Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy. Nature communications. 2024 15(1):1581. PMID: 38383524. PMCID: PMC10881965.
• Allen RM, Michell DL, Cavnar AB, [et al.]. LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8. Nature cell biology. 2022 24(12):1701-1713. PMID: 36474072. PMCID: PMC10609361.
• Michell DL, Allen RM, Cavnar AB, [et al.]. Elucidation of physico-chemical principles of high-density lipoprotein-small RNA binding interactions. The Journal of biological chemistry. 2022 298(6):101952. PMID: 35447119. PMCID: PMC9133651.
• Barman B, Sung BH, Krystofiak E, [et al., including Allen R]. VAP-A and its binding partner CERT drive biogenesis of RNA-containing extracellular vesicles at ER membrane contact sites. Developmental cell. 2022 57(8):974-994.e8. PMID: 35421371. PMCID: PMC9075344.
• Abner JJ, Franklin JL, Clement MA, [et al., including Allen RM]. Depletion of METTL3 alters cellular and extracellular levels of miRNAs containing m(6)A consensus sequences. Heliyon. 2021 7(12):e08519. PMID: 34934837. PMCID: PMC8654799.
• Wang Y, Niu A, Pan Y, [et al., including Allen RM]. Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq. Diabetes. 2021 70(10):2377-2390. PMID: 34233930. PMCID: PMC8576501.
• Ormseth MJ, Solus JF, Sheng Q, [et al., including Allen R]. Plasma miRNAs improve the prediction of coronary atherosclerosis in patients with rheumatoid arthritis. Clinical rheumatology. 2021 40(6):2211-2219. PMID: 33389220. PMCID: PMC8162679.
• Ormseth MJ, Wu Q, Zhao S, [et al., including Allen RM]. Circulating microbial small RNAs are altered in patients with rheumatoid arthritis. Annals of the rheumatic diseases. 2020 79(12):1557-1564. PMID: 32958509. PMCID: PMC7669585.
• Michell DL, Zhao S, Allen RM, [et al.]. Pervasive Small RNAs in Cardiometabolic Research: Great Potential Accompanied by Biological and Technical Barriers. Diabetes. 2020 69(5):813-822. PMID: 32312897. PMCID: PMC7171967.
• Ormseth MJ, Solus JF, Sheng Q, [et al., including Allen RM]. The Endogenous Plasma Small RNAome of Rheumatoid Arthritis. ACR open rheumatology. 2020 2(2):97-105. PMID: 31913579. PMCID: PMC7011423.
• Ormseth MJ, Solus JF, Sheng Q, [et al., including Allen RM]. Development and Validation of a MicroRNA Panel to Differentiate Between Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus and Controls. The Journal of rheumatology. 2020 47(2):188-196. PMID: 31092710. PMCID: PMC6856415.