Genetics, Cell Biology and Development
Molecular, Cellular, Developmental Biology and Genetics
The regeneration of complex body structures after injury or ablation remains poorly understood at the molecular level. In salamanders, this amazing ability includes not only the faithful regeneration of large portions of appendages or organs, but also the apparently perfect repair of even major skin lesions with no detectable scarring. This is in stark contrast to humans; wherein even minor injuries to the skin can result in significant scarring. As seen most tragically in major burn victims and in the common affliction of “diabetic foot”, this can not only be disfiguring but also functionally debilitating, often posing a lethal threat. The aim of my proposed research is to advance translational research efforts meant to improve the treatment for these skin lesions by identifying the molecular determinants underlying this evolutionary divergence. My main strategy will focus on the detailed comparative analysis of the regenerative salamander skin versus the non-regenerative mammalian skin in collaboration with Dr. Jakub Tolar (UMN). We will begin by identifying the molecular components and associated cellular functionalities that define key pathways regulating skin regeneration in the axolotl, and comparing them to repair pathways occurring in the corresponding mammalian context where scarring is a major problem. This will be driven through a top-down approach, focusing on miRNAs acting as high-level regulators of gene expression modules in salamander regeneration, and characterizing their downstream pathway components. This knowledge will then be used to carryout detailed studies of endogenous pathway functions in each system, and with the translational goal of harnessing those function to specifically promote more efficient repair processes in the mammalian context.
Murphy KA, Lechner MG, Popescu FE, Bedi J, Decker SA, Hu P, Erickson JR, O’Sullivan MG, Swier L, Salazar AM, Olin MR, Epstein AL, Ohlfest JR. An in vivo immunotherapy screen of costimulatory molecules identifies Fc- OX40L as a potent reagent for the treatment of established murine gliomas. Clin Cancer Res. 2012 Sep 1;18(17):4657-4668. PMCID: PMC3432688
Stritesky GL, Xing Y, Erickson JR, Kalekar LA, Mueller DL, Jameson SC, Hogquist KA. Murine thymic selection quantified using a novel method to capture deleted T cells. Proc Natl Acad Sci U S A. 2013 Mar 19; 110(12):4679-84. PMCID: PMC3606987
Murphy KA, Erickson JR, Forster C, Seiler C, Popescu FE, Bedi J, Hu P, Epstein AL, Ohlfest JR. CD8 independent tumor regression induced by Fc-OX40L and therapeutic vaccination in a mouse model of glioma. Submitted to J Immunol.