Zingarelli Lab

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Zingarelli Lab

Zingarelli Lab Research

The Zingarelli laboratory is focused on the investigation of the pathophysiologic mechanisms of sepsis, trauma and hemorrhagic shock, which are leading causes of morbidity and mortality in intensive care units. Dr. Zingarelli has identified putative anti-inflammatory nuclear receptors, the peroxisome proliferator activated receptors (PPARγ , PPARα and PPARδ ), and liver X receptors (LXRs), which regulate gene transcription of several cytotoxic modulators and may be important defense factors. Recent research efforts also focus on understanding the role of aging on the clinical course of infections, severe hemorrhage and trauma. The laboratory employs a multidisciplinary approach combining in vivo and in vitro experimental models in genetically modified rodents and cell lines. These models are also utilized as a translational research platform to screen novel pharmacological compounds that can modulate the molecular mechanisms of organ function. The goal is to identify specific therapeutic interventions for pediatric, adult and elderly patients.
The Zingarelli laboratory is also collaborating with several basic science and translational studies in the division of Critical Care Medicine. In collaboration with Dr. Hector Wong, the Zingarelli laboratory investigates novel biomarkers and pathways involved in sepsis pathobiology, including the role of the matrix metallo-proteinase 8 (MMP-8). In collaboration with Dr. Jennifer Kaplan, the Zingarelli laboratory evaluates the effects of obesity on the increased risk of complications after infections.
Dr. Zingarelli also collaborates on basic science studies with Dr. James A. Cook of the Medical University of South Carolina on the molecular mechanisms by which Gram-negative or Gram-positive bacteria interact with the host cells and mediate the pathological effects of infections.
Ongoing projects are primarily funded by multiple grants from the National Institutes of Health.
Publications

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2012

Standage SW, Caldwell CC, Zingarelli B, Wong HR. Reduced peroxisome proliferator-activated receptor α expression is associated with decreased survival and increased tissue bacterial load in sepsis. Shock 37: 164-169, 2012.
SolanPD, Dunsmore KE, DenenbergAG, OdomsK, Zingarelli B, Wong HR. A novel role for matrix metalloproteinase-8 in sepsis. Crit. Care Med. 40: 379-387, 2012.
Kaplan JM, NowellM, Lahni P, O’Connor M, Hake PW, Zingarelli B. Short-term high fat feeding increases organ injury and mortality after polymicrobial sepsis. Obesity 20:1995-2002, 2012.
Li P, Neubig RR, Zingarelli B, Borg K, Halushka PV, Cook JA, Fan H. Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function of Gαi2 protein. Inflammation 35: 1611-1617, 2012.

2011

Wheeler DS, Wong HR, Zingarelli B. Children are not small adults. Open Inflamm. J. 4: 4-15,2011.
Solan PD, Piraino G, Hake PW, O’Connor M, Lentsch A, Zingarelli B. Liver X receptor α activation with the synthetic ligand T0901317 reduces lung injury and inflammation after hemorrhage and resuscitation via inhibition of the NF-kB pathway. Shock 35: 367-374, 2011.
Fan H, Li P, Zingarelli B, Borg K, Halushka PV, Birnbaumer L, Cook JA. Heterotrimeric Gαi proteins are regulated by lipopolysaccharide and are anti-inflammatory in endotoxemia and polymicrobial sepsis. Biochim. Biophys. Acta 1813: 466-472, 2011.
Chima RS, Maltese G, LaMontagne T, Piraino G, Denenberg A, O’Connor M, Zingarelli B. C-peptide ameliorates kidney following hemorrhagic shock. Shock 35: 524-529, 2011.
Zingarelli B. What's New in SHOCK, March 2011? Shock 35: 217-219, 2011.
Aneja RK, Sjodin H, Gefter JV, Zingarelli B, Delude RL. Small interfering RNA mediated Poly (ADP-ribose) Polymerase-1 inhibition upregulates the heat shock response in a murine fibroblast cell line. J. Inflam. (Lond). 8: 3, 2011.
Wheeler DS, Giuliano JS, Lahni PM, Denenberg AG, Wong HR, Zingarelli B. The immunomodulatory effects of albumin in vitro and in vivo. Adv. Pharmacol. Sci. 2011: 691928, 2011.
Chima R, Hake P, Mangeshkar P, Piraino G, O’Connor M, Zingarelli B. C-peptide: a novel inhibitor of lung inflammation following hemorrhagic shock. Am. J. Physiol. Lung Cell Mol. Physiol. 300: L730-L739, 2011.
Kaplan JM, Zingarelli B. Novel Therapeutic Agents in Pediatric Sepsis: Peroxisome Proliferator Receptor γ (PPARγ) Agonists.Open Inflamm. J. 4(Suppl 1-M14): 120-124, 2011.

2010

Kaplan JM, Denenberg A, Monaco M, Gunn B, Nowell M, Wong H, Zingarelli B. Changes in peroxisome proliferator activated receptor- activity in children with septic shock. Intensive Care Med., 36: 123-130, 2010.
Zingarelli B, O’Connor M, Piraino G, Denenberg A, Hake PW. Severity of liver injury is age-dependent and correlates with changes of peroxisome proliferator activated receptor-γ activity in hemorrhagic shock. Am.J. Physiol. Gastrointest. Liver Physiol., 298: 133-141, 2010.
Fan H, Bitto A, Zingarelli B, Luttrell LM, Borg K, Halushka PV, Cook JA. Beta-Arrestin 2 negatively regulates sepsis-induced inflammation. Immunology 130: 344-351, 2010.
Chima R, Hake P, Mangeshkar P, Piraino G, O’Connor M, Zingarelli B. Ciglitazone reduces lung apoptosis by modulating the Akt pathway following hemorrhagic shock. Int. J. Clin. Exp. Med. 3: 1-9, 2010.
Zingarelli B, Piraino G, Hake PW, O’Connor M, Denenberg A, Fan H, Cook JA. PPARd regulates systemic inflammation via the NF-kB signaling pathway in polymicrobial sepsis. Am. J. Pathol. 177:1834-1847, 2010.
Kaplan JM, Hake PW, Denenberg A, Nowell M, Piraino G, Zingarelli B. Phosphorylation of extracellular signal-regulated kinases (ERK)1/2 is associated with the downregulation of peroxisome proliferator-activated receptor- during polymicrobial sepsis. Mol. Med. 16: 491-497, 2010.
Chima R, Zingarelli B. Toll-like receptor-2 and disturbances of the cardiac rhythm: life changes in a heartbeat. Crit. Care Med. 38: 2062-2063, 2010.

2009

Zingarelli B, Hake PW, O’Connor M, Burroughs TJ, Wong HR, Solomkin JS, Lentsch AB. Lung injury after hemorrhage is age-dependent: role of peroxisome proliferator activated receptor g. Crit. Care Med. 37: 1978-87, 2009.
Wheeler DS, Zingarelli B, Wheeler WJ, Wong HR. Novel pharmacologic approaches to the management of sepsis: targeting the host inflammatory response. Recent Pat. Inflamm. Allergy Drug Discov. 3: 96-112,2009.
WangX, Zingarelli B, O’Connor M, Zhang P, Adeyemo A, Wang Y, Kranias EG, Fan GC. Overexpression of Hsp20 prevents endotoxin-induced myocardial dysfunction and apoptosis via inhibition of NF-kB activation. J. Mol. Cell Cardiol. 47: 382-390, 2009.

2008

Zingarelli B, Fan H, Ashton S, Piraino G, Mangeshkar P, Cook JA. Peroxisome proliferation-activated receptor (PPAR) g is not necessary for the development of LPS-induced tolerance. Immunology 124: 51-57, 2008.
Abboud PA, Hake PW, Burroughs TJ, Odoms K, O'Connor M, Mangeshkar P, Wong HR, Zingarelli B. Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitis. Eur. J. Pharmacol. 579: 411-417, 2008.
Kuboki S, Shin T, Huber N, Eismann T, Galloway E, Schuster R, Blanchard J, Zingarelli B, Lentsch AB. Peroxisome proliferator-activated receptor-g protects against hepatic ischemia/reperfusion injury in mice. Hepatology 47: 215-224, 2008.
Wheeler DS, Lahni PM, Denenberg AG, Poynter SE, Wong HR, Cook JA, Zingarelli B. Induction of endotoxin tolerance enhances bacterial clearance and survival in murine polymicrobial sepsis. Shock 30: 267-273, 2008.
Irazuzta J, Pretzlaff RK, Decourten-Myers G, Zemlan F, Zingarelli B. Caspases inhibition decreases neurological sequelae in meningitis. Crit. Care Med. 36: 1603-1606; 2008.
Chima R, Hake P, Mangeshkar P, Piraino G, Denenberg A, Zingarelli B. Ciglitazone ameliorates lung inflammation by modulating the IKK/NF-kB pathway following hemorrhagic shock. Crit Care Med. 36: 2849-2857, 2008.
Basher F, Fan H, Zingarelli B, Borg KT, Louttrell LM, Tempel GE, Halushka PV, Cook JA. b-arrestin 2: a negative regulator of inflammatory responsesin polymorphonuclear leukocytes. Int. J. Clin. Exp. Med. 1: 32-41, 2008.
Fan H, Zingarelli B, Harris V, Tempel GE, Halushka PV, Cook JA. Lysophosphatidic acid inhibits bacterial endotoxin-induced pro-inflammatory response:potential anti-inflammatory signaling pathways. Mol. Med. 14: 422-428, 2008.

Other Significant Publications

Vish MG, Mangeshkar P, Piraino G, Denenberg A, Hake PW, O'Connor M, Zingarelli B. Proinsulin C-peptide exerts beneficial effects in endotoxic shock in mice. Crit. Care Med. 35: 1348-1355, 2007.
Zingarelli B, Hake PW, O’Connor M, Denenberg A, Wong HR, Kong S, Aronow BJ. Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly (ADP-ribose) polymerase-1. Am. J. Physiol. Heart Circ. Physiol. 286:H1408-H1415, 2004.
Zingarelli B, Sheehan M, Hake PW, O'Connor M, Denenberg A, Cook JA. Peroxisome proliferator activator receptor-g ligands, 15-deoxy-^12,14-PGJ₂ and ciglitazone, reduces systemic inflammation in polymicrobial sepsis by modulation of signal transduction pathways. J. Immunol. 171: 6827-6837, 2003.
Andreone TL, Denenberg A, O’Connor M, Hake PW, Zingarelli B. Poly (ADP-ribose) polymerase-1 regulates activation of activator protein-1 in murine fibroblasts. J. Immunol. 170: 2113-2120, 2003.
Zingarelli B, Hake PW, Yang Z, O’Connor M, Denenberg A, Wong HR. Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-B and AP-1 activation and enhances myocardial damage. FASEB J. 16: 327-342, 2002.

Contact Us

Basilia Zingarelli, MD, PhD
Professor of Pediatrics and Director of Basic Science Research
Division of Critical Care Medicine
3333 Burnet Avenue
MLC 7006
Cincinnati, OH 45229-3039
513-636-8704
basilia.zingarelli@cchmc.org
Patrick Lahni
Research Assistant IV
Division of Critical Care Medicine
3333 Burnet Avenue
MLC 7006
Cincinnati, OH 45229-3039
513-636-8710
patrick.lahni@cchmc.org

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