Critical Care Medicine Research
Zingarelli Lab

Zingarelli Research Lab

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. A particular goal of her research has been to define the mechanisms of metabolic recovery and innate immune responses mediated by the nuclear hormone receptors peroxisome proliferator activated receptors (PPARs) and by the AMP activated protein kinase (AMPK), which are major regulators of the glucose and lipid metabolism. In dissecting the dysmetabolic mechanisms of organ injury, the Zingarelli laboratory has discovered that key molecules of the mitochondrial retrograde signaling, such as humanin, may contribute to the regulation of metabolic recovery of damaged organs. 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 at Cincinnati Children’s Hospital. In collaboration with Takahisa Nakamura, PhD of the Division of Endocrinology and Jennifer Kaplan, MD, MS, of the Division of Critical Care Medicine, the Zingarelli Laboratory explores critical pathways of cell signaling and reprogramming of innate immune responses through release of extracellular vesicles in obesity and sepsis.

Ongoing projects are primarily funded by multiple grants from the National Institutes of Health.

Publications

Pei, F; Yao, RQ; Ren, C; Bahrami, S; Billiar, TR; Chaudry, IH; Chen, DC; Chen, XL; Cui, N; Fang, XM; et al. Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression. Military Medical Research. 2022; 9.

Urban, C; Hayes, HV; Piraino, G; Wolfe, V; Lahni, P; O’Connor, M; Phares, C; Zingarelli, B. Colivelin, a synthetic derivative of humanin, ameliorates endothelial injury and glycocalyx shedding after sepsis in mice. Frontiers in Immunology. 2022; 13.

Odum, JD; Standage, S; Alder, M; Zingarelli, B; Devarajan, P; Wong, HR. Candidate Biomarkers for Sepsis-Associated Acute Kidney Injury Mechanistic Studies. Shock. 2022; 57:687-693.

Hayes, HV; Wolfe, V; O’connor, M; Levinsky, NC; Piraino, G; Zingarelli, B. Deficiency of AMPKα1 Exacerbates Intestinal Injury and Remote Acute Lung Injury in Mesenteric Ischemia and Reperfusion in Mice. International Journal of Molecular Sciences. 2021; 22.

Wang, P; Mu, X; Zhao, H; Li, Y; Wang, L; Wolfe, V; Cui, SN; Wang, X; Peng, T; Zingarelli, B; et al. Administration of GDF3 Into Septic Mice Improves Survival via Enhancing LXRα-Mediated Macrophage Phagocytosis. Frontiers in Immunology. 2021; 12.

Zingarelli, B. First Do No Harm: A Proposal of an Expert-Guided Framework of Surrogate Humane Endpoints in Preclinical Models of Acute Lung Injury. Critical Care Medicine. 2021; 49:373-375.

Arora, K; Lund, JR; Naren, NA; Zingarelli, B; Naren, AP. AC6 regulates the microtubule-depolymerizing kinesin KIF19A to control ciliary length in mammals. Journal of Biological Chemistry. 2020; 295:14250-14259.

Wu, Y; Li, P; Goodwin, AJ; Cook, JA; Halushka, PV; Zingarelli, B; Fan, H. miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis. Journal of Infectious Diseases. 2020; 222:1037-1045.

Morris, MC; Niziolek, GM; Blakeman, TC; Stevens-Topie, S; Veile, R; Heh, V; Zingarelli, B; Jr, RD; Branson, RD; Goodman, MD. Intrathoracic Pressure Regulator Performance in the Setting of Hemorrhage and Acute Lung Injury. Military Medicine. 2020; 185:e1083-e1090.

Kikuchi, S; Piraino, G; O'Connor, M; Wolfe, V; Ridings, K; Lahni, P; Zingarelli, B. Hepatocyte-Specific Deletion of AMPKα1 Results in Worse Outcomes in Mice Subjected to Sepsis in a Sex-Specific Manner. Frontiers in Immunology. 2020; 11.

Zhou, Y; Li, P; Goodwin, AJ; Cook, JA; Halushka, PV; Chang, E; Zingarelli, B; Fan, H. Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury. Critical Care. 2019; 23.

Levinsky, NC; Mallela, J; Opoka, AM; Harmon, K; Lewis, HV; Zingarelli, B; Wong, HR; Alder, MN. The olfactomedin-4 positive neutrophil has a role in murine intestinal ischemia/reperfusion injury. FASEB Journal. 2019; 33:13660-13668.

Kitzmiller, L; Ledford, JR; Hake, PW; O'Connor, M; Piraino, G; Zingarelli, B. Activation of AMP-Activated Protein Kinase by A769662 Ameliorates Sepsis-Induced Acute Lung Injury in Adult Mice. Shock. 2019; 52:540-549.

Lautz, AJ; Zingarelli, B. Age-Dependent Myocardial Dysfunction in Critically Ill Patients: Role of Mitochondrial Dysfunction. International Journal of Molecular Sciences. 2019; 20.

Zingarelli, B; Coopersmith, CM; Drechsler, S; Efron, P; Marshall, JC; Moldawer, L; Wiersinga, WJ; Xiao, X; Osuchowski, MF; Thiemermann, C. Part I: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Study Design and Humane Modeling Endpoints. Shock. 2019; 51:10-22.

Osuchowski, MF; Hellman, J; Huber-Lang, M; Libert, C; Remick, DG; Thiemermann, C; Zingarelli, B. The Response to the Letter to the Editor Titled: "Is Triple Self-plagiarism "OK " If Only Made Transparent? " by Volker R Jacobs, MD, MBA. Shock. 2019; 51:140-141.

Lewis, H; Piraino, G; Wolfe, V; Zingarelli, B. 1822. Critical Care Medicine. 2019; 47.

Urban, C; Piraino, G; Wolfe, V; Hake, P; Zingarelli, B. 1817. Critical Care Medicine. 2019; 47.

Lautz, A; Chintala, H; Zingarelli, B; Wong, H. 1813. Critical Care Medicine. 2019; 47.

Osuchowski, MF; Ayala, A; Bahrami, S; Bauer, M; Boros, M; Cavaillon, J; Chaudry, IH; Coopersmith, CM; Deutschman, CS; Drechsler, S; et al. Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): An International Expert Consensus Initiative for Improvement of Animal Modeling in Sepsis. Shock. 2018; 50:377-380.

Osuchowski, MF; Ayala, A; Bahrami, S; Bauer, M; Boros, M; Cavaillon, J; Chaudry, IH; Coopersmith, CM; Deutschman, C; Drechsler, S; et al. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis. Intensive Care Medicine Experimental. 2018; 6.

Li, P; Zhou, Y; Goodwin, AJ; Cook, JA; Halushka, PV; Zhang, XK; Wilson, CL; Schnapp, LM; Zingarelli, B; Fan, H. Fli-1 Governs Pericyte Dysfunction in a Murine Model of Sepsis. Journal of Infectious Diseases. 2018; 218:1995-2005.

Kaplan, JM; Zingarelli, B; Krallman, K; Girdwood, ST; Lagory, D; Mizuno, T; Fei, L; Wong, HR; Vinks, AA. Phase 1 safety and pharmacokinetic study on the use of pioglitazone in critically ill patients with sepsis: a randomized clinical trial. Intensive Care Medicine. 2018; 44:2006-2008.

Ayalon, I; Shen, H; Williamson, L; Stringer, K; Zingarelli, B; Kaplan, JM. Sepsis Induces Adipose Tissue Browning in Nonobese Mice But Not in Obese Mice. Shock. 2018; 50:557-564.

Inata, Y; Piraino, G; Hake, PW; O'Connor, M; Lahni, P; Wolfe, V; Schulte, C; Moore, V; James, JM; Zingarelli, B. Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR. American Journal of Physiology - Heart and Circulatory Physiology. 2018; 315:H826-H837.

Osuchowski, MF; Ayala, A; Bahrami, S; Bauer, M; Boros, M; Cavaillon, J; Chaudry, IH; Coopersmith, CM; Deutschman, C; Drechsler, S; et al. Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis. Infection. 2018; 46:687-691.

Contact Us

A photo of Basilia Zingarelli.

Basilia Zingarelli, MD, PhD

Professor, UC Department of Pediatrics

Director of Basic Science Research, Division of Critical Care Medicine , Cincinnati Children's Hospital Medical Center

Mailing Address:
3333 Burnet Avenue
MLC 7006
Cincinnati, OH 45229-3039

Phone: 513-636-8704
Email: basilia.zingarelli@cchmc.org

Patrick Lahni
Manager, Laboratory Services
Division of Critical Care Medicine

Mailing Address:
3333 Burnet Avenue
MLC 7006
Cincinnati, OH 45229-3039

Phone: 513-636-8710
Email: patrick.lahni@cchmc.org