Qing Guo, MD, PhD


Professor of Physiology, The University of Oklahoma Health Sciences Center (OUHSC), College of Medicine.
Faculty member in the Physiology, Neuroscience, and GPiBS Graduate Programs at OUHSC.

Current Special Research Interests:

Intrinsic and Extrinsic Mechanisms of Neuronal Cell Death and Survival in Neurodegenerative Diseases and Ischemic Stroke.
Renoprotective Pathways in Diabetic Nephropathy and Renal Injury Associated with Ischemia/Reperfusion.

Education and Training:
  • M.D. Hebei Medical College, China.
  • M.S. Military Medical University, Chongqing, China.
  • Ph.D. PLA General Hospital, Beijing, China.
  • Postdoctoral Scholar: The University of Kentucky, Lexington, Kentucky, USA.
Resarch Summary: 
  • Presenilin Mutations and Pathogenesis of Early Onset Alzheimer’s Disease.
    Mutations in the presenilin‐1 (PS1) gene on chromosome 14 are causally
    linked to many cases of early‐onset inherited AD. Work by Dr. Guo and his
    colleagues has contributed to our understanding of a number of mechanisms
    for dementia of Alzheimer’s type caused by the heritable alterations of
    genetic information in presenilin proteins, which included the investigation
    of neuronal cell death process in the first mouse "knock‐in" model of a
    naturally occurring presenilin‐1 mutation responsible for an early‐onset form
    of Alzheimer disease (AD). PS1 mutant knock‐in mice (PS1M146VKI) express
    the PS1 M146V targeted allele at normal physiological levels. We found that
    these mice were hypersensitive to seizure‐induced synaptic degeneration
    and necrotic neuronal death in the hippocampus. These findings establish
    the first direct link between a genetic defect that causes AD and excitotoxic
    neuronal degeneration, and indicate new avenues for therapeutic
    intervention in AD patients. Additional studies further identify the
    involvement of perturbed intracellular calcium homeostasis and enhanced
    oxyradical production induced by PS‐1 mutations.

  • Par‐4 and AATF as Novel Mediators of Cell Death and Survival in Tissue
    Injuries Induced by Ischemia/Reperfusion. Par‐4 (prostate apoptosis
    response‐4) is a leucine zipper protein linked to apoptotic cell death. Work in
    our lab found that Par‐4 is involved in protein‐protein interactions that are
    essential for sensitization of cells to death in models of tissue injuries
    induced by ischemia/reperfusion (I/R). In fact, is an early mediator of renal
    cell injury in acute renal failure. Apoptosis antagonizing transcription factor
    (AATF) blocks Par‐4 and confers potent cytoprotective activity against
    oxidative and necroptotic damage induced by ischemia/reperfusion. AATF
    and Par‐4 may represent potential candidates for therapeutic intervention in
    ischemic tissue injury. We found that AATF and Par‐4 also participate in
    multiple aspects of neurodegeneration by altering beta‐secretase mediated
    cleavage of the Alzheimer’s amyloid precursor protein, choline uptake, and
    neurosynaptic degeneration in ALS‐linked mice and models of brain trauma.
  • An Extrinsic Signaling Pathway Mediated by Secreted ATTF is indicated in
    Regulation of Cell Death and Survival. As a transcription factor, AATF often
    functions as an intracellular protein located in cytoplasmic and/or nuclear
    compartments. However, we have unexpectedly noted that a significant
    amount of intracellular AATF protein was secreted as a part of cellular stress
    responses. Secreted AATF (sAATF) may interacts with specific cell surface
    receptor proteins involved in signaling of cell death and/or survival. For
    example, sAATF appears to be a potent blocker of the cell surface TLR4 (Tolllike
    receptor‐4) receptors. Of importance, a small extracellular AATF peptide,
    termed SAP‐12 in my lab, possesses a greater potency and broader effective
    dose range than the full length sAATF. These findings suggest that SAP‐12 may
    have broad therapeutic applications in multiple organ systems because the
    small peptides can be synthesized in large quantities, and its small size reduces
    the chance for inducing non‐specific immune responses from the host, and
    may provide a unique opportunity for delivery across the blood‐brain barrier.

  Recent and Relevant Publications:

  • Payette DJ, Xie J, Shirwany N, Guo Q. Exacerbation of apoptosis of cortical
    neurons following traumatic brain injury in par‐4 transgenic mice. Int J Clin Exp
    2008 Jan 1;1(1):44‐56.
  • Xie J, Guo Q. Apoptosis antagonizing transcription factor protects renal tubule
    cells against oxidative damage and apoptosis induced by ischemia‐reperfusion. J
    Am Soc Nephrol.
    2006 Dec;17(12):3336‐46.
  • Xie J, Guo Q. Par‐4 is a novel mediator of renal tubule cell death in models of
    ischemia‐reperfusion injury. Am J Physiol Renal Physiol. 2007 Jan;292(1):F107‐
  • Xie J, Guo Q. PAR‐4 is involved in regulation of beta‐secretase cleavage of the
    Alzheimer amyloid precursor protein. J Biol Chem. 2005 Apr 8;280(14):13824‐32.
  • Xie J, Guo Q. Par‐4 inhibits choline uptake by interacting with CHT1 and reducing
    its incorporation on the plasma membrane. J Biol Chem. 2004 Jul
  • Guo Q, Xie J. AATF inhibits aberrant production of amyloid beta peptide 1‐42 by
    interacting directly with Par‐4. J Biol Chem. 2004 Feb 6;279(6):4596‐603. 
  • Guo Q, Fu W, Sopher BL, Miller MW, Ware CB, Martin GM, Mattson MP.
    Increased vulnerability of hippocampal neurons to excitotoxic necrosis in
    presenilin‐1 mutant knock‐in mice. Nat Med. 1999 Jan;5(1):101‐6.
  • Guo Q, Sebastian L, Sopher BL, Miller MW, Glazner GW, Ware CB, Martin GM,
    Mattson MP. Neurotrophic factors [activity‐dependent neurotrophic factor
    (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic
    neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U
    S A.
    1999 Mar 30;96(7):4125‐30.
  • Guo Q, Fu W, Xie J, Luo H, Sells SF, Geddes JW, Bondada V, Rangnekar VM,
    Mattson MP. Par‐4 is a mediator of neuronal degeneration associated with the
    pathogenesis of Alzheimer disease. Nat Med. 1998 Aug;4(8):957‐62.
  • Guo Q, Robinson N, Mattson MP. Secreted beta‐amyloid precursor protein
    counteracts the proapoptotic action of mutant presenilin‐1 by activation of NFkappaB
    and stabilization of calcium homeostasis. J Biol Chem. 1998 May
  • Guo Q, Christakos S, Robinson N, Mattson MP. Calbindin D28k blocks the
    proapoptotic actions of mutant presenilin 1: reduced oxidative stress and
    preserved mitochondrial function. Proc Natl Acad Sci U S A. 1998 Mar
  • http://find.ouhsc.edu/Faculty.aspx?FacultyID=744

Current Funding Information With Agency, Type of Grant, Title, Role in the Grant:

  • Oklahoma Center for the Advancement of Science and Technology (OCAST)
    Health Research Program Grant
    Unconventional Neuroprotective Actions of sAATF in Ischemic Brain Injury.
    GUO: PI
  • Harold Hamm Diabetes Center
    Seed Grant
    AATF in Diabetic Nephropathy
    GUO: PI
    AATF and Renal Protection
    GUO: PI
    Regulation of APP processing by Par‐4
    GUO: PI
  • The Alzheimer's Association
    Regulation of ChAT activity in cholinergic neurons by Par‐4
    GUO: PI
  • The Alzheimer's Association
    Counteracting Neuronal Degeneration in Alzheimer's Disease by Inhibition of Par‐4
    GUO: PI

Phone: (405) 271-2226 ext. 56268
Mailing Address: Department of Physiology, The University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB Rm. 607, Oklahoma City, Oklahoma 73104 U.S.A.