The Young Laboratory is focused on understanding the biology of adult stem cells within the context of two broad biological processes--malignancy and regeneration. The role of adult stem cells to modulate repair and regeneration is of great interest. Our work focuses on gaining a better understanding of bone marrow derived stem cells using both mouse and human cells. Specifically, we are committed to understanding the characteristics of stem cell progenitors, their differentiation, the mechanism by which stem cells mediate regeneration and also the host/stem cell interactions.

Project 1- Mesenchymal stem cells hold much promise as tools to mediate repair. We have recently identified that Wnt pathway inhibition regulates MSC biology. We use mouse models of myocardial infarction or pressure overload hypertrophy (as a heart failure model) to study the role of wnt modulation in MSC-mediated repair. Other projects are focused on understanding the unique metabolism of stem cells that enable engraftment in wound sites and improving our knowledge of the paracrine profile of stem cells that mediate tissue repair.  Our hope is to understand how to modulate endogenous MSCs after injury to control repair and regeneration.

Project 2-Bone marrow derived endothelial progenitor cells (EPCs) are derived from both committed and uncommitted hematopoietic cells. We have characterized myeloid to endothelial plasticity over the last few years and have focused our attention on the mechanism of this plasticity. We have recently identified TNF as a modulator of endothelial differentiation. Moreover, we have also begun to better understand the role of these myelod/endothelial cells in cancer and regeneration.

Project 3 -Our vascular system is impacted by both physiologic and pathologic biomechanical stress. We have identified that SPRR3 is a mechanosensitive protein expressed by vascular smooth muscle cells and have begun to study its role in the cardiovascular system using a mouse knockout model

Publications

Featured publications

  1. Membrane TNF-alpha-activated programmed necrosis is mediated by Ceramide-induced reactive oxygen species. Ardestani S, Deskins DL, Young PP (2013) J Mol Signal 8(1): 12
    › Primary publication · 24180579 (PubMed) · PMC3895838 (PubMed Central)
  2. Brown Recluse spider bite mediated hemolysis: clinical features, a possible role for complement inhibitor therapy, and reduced RBC surface glycophorin A as a potential biomarker of venom exposure. Gehrie EA, Nian H, Young PP (2013) PLoS One 8(9): e76558
    › Primary publication · 24086749 (PubMed) · PMC3785411 (PubMed Central)
  3. Longer storage duration of red blood cells is associated with an increased risk of acute lung injury in patients with sepsis. Janz DR, Zhao Z, Koyama T, May AK, Bernard GR, Bastarache JA, Young PP, Ware LB (2013) Ann Intensive Care 3(1): 33
    › Primary publication · 24059842 (PubMed) · PMC3848804 (PubMed Central)
  4. Membrane versus soluble isoforms of TNF-α exert opposing effects on tumor growth and survival of tumor-associated myeloid cells. Ardestani S, Li B, Deskins DL, Wu H, Massion PP, Young PP (2013) Cancer Res 73(13): 3938-50
    › Primary publication · 23704210 (PubMed) · PMC3702680 (PubMed Central)
  5. Human mesenchymal stromal cells: identifying assays to predict potency for therapeutic selection. Deskins DL, Bastakoty D, Saraswati S, Shinar A, Holt GE, Young PP (2013) Stem Cells Transl Med 2(2): 151-8
    › Primary publication · 23362238 (PubMed) · PMC3659751 (PubMed Central)
  6. Blood Group A antigen expression on cardiac endothelium is highly individualized: possible implications for transplantation. Gehrie EA, Cates JM, Nian H, Olson SJ, Young PP (2013) Cardiovasc Pathol 22(4): 251-6
    › Primary publication · 23290353 (PubMed) · PMC4795169 (PubMed Central)
  7. A physiological role for connective tissue growth factor in early wound healing. Alfaro MP, Deskins DL, Wallus M, DasGupta J, Davidson JM, Nanney LB, A Guney M, Gannon M, Young PP (2013) Lab Invest 93(1): 81-95
    › Primary publication · 23212098 (PubMed) · PMC3720136 (PubMed Central)
  8. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. Alfaro MP, Vincent A, Saraswati S, Thorne CA, Hong CC, Lee E, Young PP (2010) J Biol Chem 285(46): 35645-53
    › Primary publication · 20826809 (PubMed) · PMC2975189 (PubMed Central)
  9. Atheromas feel the pressure: biomechanical stress and atherosclerosis. Pyle AL, Young PP (2010) Am J Pathol 177(1): 4-9
    › Primary publication · 20558573 (PubMed) · PMC2893643 (PubMed Central)
  10. Proteomic analysis of osteogenic sarcoma: association of tumour necrosis factor with poor prognosis. Cates JM, Friedman DB, Seeley EH, Dupont WD, Schwartz HS, Holt GE, Caprioli RM, Young PP (2010) Int J Exp Pathol 91(4): 335-49
    › Primary publication · 20353421 (PubMed) · PMC2962892 (PubMed Central)