Contact

Location: 300.26 - STRF

Department

Surgery

Shireman, Paula K., M.D.

Professor, Dielmann Chair in Surgery

Personal Statement:

Dr. Shireman is a clinically active vascular surgeon with broad experience in diabetes, atherosclerosis, tissue regeneration, wound healing and the role of inflammatory cells in these processes. Her long term goal is to improve the care of patients with vascular disease and traumatic injuries. Her research team has focused on muscle regeneration, collateral artery formation, angiogenesis, imaging modalities to study extremity injuries and macrophage interactions with endothelial cells and myogenic progenitor cells. Dr. Shireman has been fascinated by macrophage plasticity and the ability to differentiate in response to environmental factors. Two of their recent publications (below) have focused on macrophage polarization. They are concentrating on microRNA-regulation of macrophage polarization as a possible therapeutic to improve wound healing. These studies have provided exciting preliminary data suggesting a major role for mRNAs.

Education

M.D., Medicine at Indiana University School of Medicine, Indianapolis, IN

Research

Keywords: Bone Marrow-Derived Cells; Skeletal Muscle Regeneration

Research interests:
The Shireman 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. Another application of altering macrophage polarization is in inhibiting cancer growth and these possibilities are also being actively explored.

Awards & Accomplishments

  • NIH Reviewer for the Bioengineering, Technology and Surgical Sciences (BTSS) Study Section
  • National Research Committee, American Heart Association
  • Dielmann Chair in Surgery

Affiliations

  • Fellow, American Heart Association
  • Fellow, American College of Surgeons
  • Distinguished Fellow, Society for Vascular Surgery
  • American Society for Investigative Pathology (ASIP)
  • American Surgical Association
  • North American Vascular Biology Organization (NAVBO)
  • Society of University Surgeons

Publications

View Complete List of Publications

  1. Melton DW, McManus LM, Gelfond JAL, Shireman PK. Temporal phenotypic features distinguish polarized macrophages in vitro Autoimmunity 2015 May;48(3):161-176.
  2. Shireman PK, Rasmussen TE, Jaramillo CA, Pugh MJ. VA vascular injury study (VAVIS): VA-DoD extremity injury outcomes collaboration. BMC Surg 2015 Feb;3(15):1-13.
  3. Fearing CM, Melton DW, Lei X, Hancock H, Wang H, Sarwar Z, Porter L, McHale M, McManus LM, Shireman PK. Increased adipocyte area in injured muscle with aging and impaired remodeling in female mice, In Press J Gerontology A Biol Sci Med Sci 2015
  4. 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 Sep;44(21):42-51.
  5. 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. PMCID: PMC3110887 Physiol Genomics 2011 May;43(10):621-630.
  6. 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. PMCID: PMC2944434 Am J Physiol Regul Integr Comp Physiol 2010 Sep;299(3):R832-R842.
  7. Sun D, Martinez C, 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. PMCID: PMC2630778 FASEB J 2009 Feb;23(2):382-395.
  8. Chen Y, Gelfond JA, McManus LM, Shireman PK. Reproducibility of quantitative RT-PCR array in miRNA expression profiling and comparison with microarray analysis. PMCID: PMC2753550 BMC Genomics 2009;10:407-417.
  9. Ochoa O, Sun D, Reyes-Reyna SM, Waite LL, Michalek JE, McManus LM, Shireman PK. Delayed angiogenesis and VEGF production in CCR2-/- mice during impaired skeletal muscle regeneration. PMID: 17522124 Am J Physiol Regul Integr Comp Physiol 2007 Aug;293(2):651-661.
  10. Shireman PK, Contreras-Shannon V, Ochoa O, Karia BP, Michalek JE, McManus LM. MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration. J Leukoc Biol 2007 Mar;81:775-785.