Dr. Paula K. Shireman's lab studies the role of bone marrow-derived cells in angiogenesis and skeletal muscle regeneration and how aging affects these phenomena. Macrophage polarization states exhibit different functions in muscle regeneration. MicroRNAs (miRNAs) are small, noncoding RNAs that inhibit gene expression, thereby regulating many processes, including immune cell differentiation.
However, the regulating effect of miRNAs on macrophage polarization, and the subsequent effect on muscle regeneration, has not been elucidated.
As a clinically active vascular surgeon, my long term goal is to develop therapies to enhance muscle regeneration and tissue engineering, thereby reducing limb amputations.
Modulating macrophage polarization could become a therapeutic intervention in muscle regeneration and disease states associated with acute and chronic inflammation.
Melton DW, McManus LM,
Gelfond JAL, Shireman PK. Temporal phenotypic features distinguish polarized macrophages in vitro. Autoimmunity, 48(3):161-76,
Wang H, Melton DW, Porter L, Sarwar ZU, McManus LM, Shireman PK. Altered macrophage phenotype transition impairs skeletal muscle regeneration. Am J Pathol. 2014 Apr;184(4):1167-84.
Chen Y, Melton DW, Gelfond JA, McManus LM, Shireman PK. MiR-351
transiently increases during muscle regeneration and promotes
progenitor cell proliferation and survival upon differentiation. Physiol Genomics. 2012 Nov 1;44(21):1042-51.
Chen Y, Gelfond J, McManus LM, Shireman PK. Temporal
microRNA expression during in vitro myogenic progenitor cell
proliferation and differentiation: regulation of proliferation by
miR-682. Physiol Genomics. 2011 May 1;43(10):621-30.
Martinez CO, McHale MJ, Wells JT, Ochoa O, Michalek JE, McManus LM, Shireman PK. Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment. Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R832-42.
Sun D, Martinez CO, Ochoa O, Ruiz-Willhite L, Bonilla JR, Centonze VE, Waite LL, Michalek JE, McManus LM, Shireman PK. Bone marrow-derived cell regulation of skeletal muscle regeneration. FASEB J. 2009 Feb;23(2):382-95.