Research Mentors | Systems Biology and Physiology PhD | Education

Karthickeyan Chella Krishnan, PhD

Konstantinos Drosatos, MSc, PhD, FAHA

Guo-Chang Fan, PhD

Chen Gao, PhD

Judith Heiny, PhD

James P. Herman, PhD

Departmental Chair & Professor
Pharmacology, Physiology, and Neurobiology
Medical Sciences Building 5259/ Reading Campus, Building A-145

Office Phone: 513-558-5636
hermanjs@ucmail.uc.edu

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Description of Research:
My major research interests explore structural, functional and molecular biological principles underlying stress integration, with an emphasis on delineating mechanisms linking stress with mental illness and cognitive disorders. The organismal ‘stress response’ represents an integrated physiological process whose primary goal is to redistribute energy to meet a real or perceived challenge. As a consequence, stress engages a variety of physiological and neural processes with the ultimate objective of achieving optimal survival value, including the hypothalamo-pituitary-adrenocortical axis, the autonomic nervous system, and brain stress regulatory pathways that coordinate the behavior of the organism to fit desired outcomes. While initially adaptive, prolonged stress causes aberrant neuroplastic events in brain that have a long-term negative impact on physiology and behavior. My research is geared toward understanding the mechanisms underlying initiation of these neuroplastic events and their consequences on the individual. We have developed chronic stress paradigms that model physiological, metabolic and behavioral symptoms of depression (e.g., glucocorticoid dyshomeostasis; helplessness; anhedonia; cardiovascular pathology; visceral obesity) and PTSD (late-emerging, long-lasting potentiation of conditioned fear; late-emerging metabolic pathologies). We exploit these models to discover neurocircuit mechanisms mediating the deleterious effects of stress on neuroplasticity and behavior, focusing on corticolimbic pathways. Our work employs a broad spectrum of methods, including region/tissue-specific knockout in mice and rats; viral vector gene knockdown/ overexpression/CRISPR to modify gene expression in discrete brain regions; chemogenetic/optogenetic methods to modify brain activation in a site and projection specific manner; genomic approaches to understanding gene and epigenetic (microRNA) expression patterns in identified cell populations; mathematical modeling and bioinformatics; and state-of-the-art neuroanatomical approaches.

Keywords: stress neurobiology, behavioral neuroscience, CNS neurocircuitry: signaling mechanisms, prefrontal cortex, neurobiology of disease, computational neuroscience, multi-omics, neuropharmacology, neurophysiology, stress and cardiovascular disease

Katharine Hobbing, PhD

Christian Hong, PhD

Terry L. Kirley, PhD

John N. Lorenz, PhD

Bryan Mackenzie, PhD

A. John MacLennan , PhD

Jayme McReynolds, PhD

Andrew B. Norman, PhD

Professor
Dept of Pharmacology, Physiology, Neurobiology

Cardiovascular Research Center 5938
Office Phone: 513-558-6654
normanab@ucmail.uc.edu

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Description of Research:
The focus of the Norman Laboratory is translational research to develop medications for the treatment of cocaine abuse.

Drug self-administration by animals is a valid model of human addictive behavior. It has long been considered axiomatic that drugs of abuse are self-administered because of their pleasurable (hedonic or euphoric) effects, which in turn makes these drugs positively reinforcing. Unfortunately, these assumptions result in well-known paradoxes and the idea that reinforcement plays any significant role in maintained self-administration behavior is of limited utility.

The Norman laboratory has developed a quantitative pharmacological theory of self-administration behavior in which cocaine-induced responding occurs only while drug concentrations are within a specific range. The core of our model of the maintenance phase of drug self-administration is the equation: T=ln(1+DU/DST)·t1/2/ln2, which defines the inter-injection intervals (T) in terms of only three parameters: the unit dose of cocaine (DU), the elimination half-life of cocaine (t1/2) and the satiety threshold (DST). This latter parameter is defined as the highest concentration of drug at which self-administration occurs. This simple model is the first to successfully define a seemingly complex behavior in terms of purely physical parameters.

This pharmacological paradigm represents a scientifically rigorous foundation for generating testable hypotheses about the biological basis of addictive behavior. More importantly, it provides a rational basis for the development of medications for drug addiction. To this end an active collaboration with Dr. Jim Ball has developed a human anti-cocaine monoclonal antibody as a pharmacokinetic antagonist of cocaine, which is intended as an immunotherapy to prevent relapse in cocaine abusers.

The Norman lab is also using drug self-administration behavior as a bioassay system to measure the absolute pharmacodynamic and pharmacokinetic potencies of receptor antagonists as a basis for developing antagonist based pharmacotherapies.

Keywords: pharmacology, cocaine disorder, addiction, satiety threshold, self-administration behavior, anti-cocaine antibody

Diego Perez-Tilve, PhD

Sarah K. Pixley, PhD

Associate Professor
Dept of Pharmacology, Physiology, Neurobiology
Medical Sciences Building 4206A
Office Phone: 513-558-6086

pixleysk@ucmail.uc.edu

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Description of Research:
Dr. Pixley’s lab coordinates with an interdisciplinary group that spans UC colleges, US universities, international partners and industrial partners. For over 10 years, this work has been part of an NSF Engineering Research Center (ERC) funding mechanism. This ERC was entitled Revolutionizing Metallic Biomaterials. Three US universities, several industrial partners and an international partner were involved. The Pixley lab focus has been on novel applications of metallic biomaterials, particularly to repair damaged nervous tissues. The particular application pursued to date has been peripheral nerve regeneration. While the ERC funding has now ended, the lab continues its partnership with engineers to advance biomedical repairs. Our most recent partnership is with an engineering team in Israel.

When substantial injuries occur that result in complete loss of peripheral nerve segments, surgical intervention is required. A scaffold is used to replace the lost segments and reconnect the two cut nerve endings. We seek to develop “man-made” or biomaterial scaffolds to avoid the hazards and dangers of using autografts (nerves from the same patient). In particular, we are interested in using a unique material, biodegradable metals (magnesium (Mg) and zinc (Zn)) as part of scaffolds. These metals have promise to provide a physical pathway to safely guide and support regenerating cells as they cross an injury gap in a nerve and regenerate a nerve segment.

Our research has shown that Mg and now Zn metal, in microfilament forms, have great promise to provide this type of contact guidance. Our goals now are to continue to refine the use of these biomaterials, as well as to develop a better understanding of the mechanisms by which nerve regeneration adapts to these unusual biomaterials, as a means to understand nerve regeneration and nerve repair in general.

Techniques used in the lab involve animal surgery, behavioral studies and then histological analyses. We also use cell culture to study the cellular responses to the metals, their ions and other degradation products.

Keywords: tissue regeneration after injury, peripheral nerve regeneration, skin wound healing, biodegradable metals, nerve repair scaffolds, tissue implants and engineering, foreign body tissue responses, Schwann cells, rodent cell culture and in vivo experiments, tissue implants and engineering

Teresa Reyes, PhD

Renu Sah, PhD

Jo El Schultz, PhD

Associate Professor
Dept of Pharmacology, Physiology, and Neurobiology
Medical Sciences Building 5157
Office Phone: 513-558-9754
schuljo@ucmail.uc.edu

CV in UC research Directory

Graduate Director: Molecular, Cellular, & Biochemical Pharmacology PhD Degree Program and System Biology and Physiology PhD Degree Program

Description of Research:
The interests of my research program are to elucidate the signaling mechanisms involved in cardiac pathophysiology, especially in relation to cardioprotection (heart protecting itself against injury due to ischemia) and heart failure. Our approach involves the utilization of transgenic and gene-targeted mice with pertubations of specific receptors, endogenous factors, and signal transduction cascades in the heart. This allows us to relate changes in the action of single gene products with specific alterations of cardiac biochemistry, physiology and pathophysiology in vivo. Both in vivo and in vitro physiological approaches are utilized in my lab to elucidate the contribution of the opioid and growth factor receptor systems to cardiac pathophysiology. We routinely employ echocardiography, work-performing and Langendorff whole heart preparations, in vivo hemodynamic measurements, and isolation and analysis of cardiomyocytes. In addition, a number of surgical techniques (aortic banding, coronary artery ligation, catheterizations) are used in my laboratory. Throughout these studies, pharmacological, histological, biochemical, and state-of-the art molecular biology assays are employed, and include PCR for mouse genotype determination, Northern blot and quantitative real-time PCR analysis of mRNA expression, and protein analysis via Western blot, ELISA and immunostaining. Genomic and proteomic tools, including DNA microarrays, will be implemented in the lab to further characterize or identify known and novel mechanism(s) of opioid- and growth factor-mediated cardiovascular physiology and pathology.

Keywords: cardiovascular, growth factors, opioids and opiates, ischemia, vascular growth, heart failure

Nicholas M. Timme, PhD

Yvonne M. Ulrich-Lai, PhD

Hong-Sheng Wang, PhD

Eric S. Wohleb, PhD

Roger Worrell, PhD

Tongli Zhang, PhD

Zalfa Abdel-Malek, PhD

Sandra Andorf, PhD.

Bruce J. Aronow, PhD

Mark L. Baccei, PhD.

Artem Barski, PhD

Thomas L Beck, PhD.

Joshua B. Benoit, PhD

Joseph P. Broderick, MD

Cristina Cebrian, PhD

Laura Conforti, PhD.

Professor
Dept of Internal Medicine - Nephrology & Hypertension
Medical Sciences Building 6115
Office Phone: 513-558-5471
conforl@ucmail.uc.edu

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Description of Research:

My laboratory specializes in immune cell function and the mechanisms that control the ability of T and NK cells to perform effector functions in the context of cancer and autoimmunity. Our research focuses on ion channels and the membrane mechanisms that regulate the activation and function of these cells. Ion channels, located on the membrane of immune cells, regulate calcium homeostasis and associated effector functions and gene expression.

Our main focus areas are:

1. Role of ion channels in immune surveillance and the response to immunotherapies in cancer patients. This research focuses on the role of the tumor microenvironment (TME) in cancer immune escape and the resistance to immunotherapies. We have discovered that ion channels control the anti-tumor capabilities of cytotoxic T cells and mediate the immunosuppressive effects of hypoxia, adenosine, PDL1 in the TME. We recently discovered that these channels are involved in the resistance to immune checkpoint therapies. These studies have contributed to establishing ion channels as new elements of immunosuppression in cancer and have opened new venues for investigation targeted toward developing novel cancer immunotherapies. Lately, we have expanded our research interest to exosomes, important immune suppressive mediators of the TME.

2. Role of ion channels in human T lymphocyte dysfunction in autoimmunity and infectious diseases. Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects predominantly women and is characterized by a broad variety of clinical symptoms such as glomerulonephritis and central nervous system impairment. We have shown that human T lymphocytes of SLE patients present with a characteristic defect in potassium channel behavior. Recently, we have extended our studies to COVID-19, where an exaggerated T cell function is associated with the cytokine storm, an excessive production of proinflammatory cytokines that contributes to acute lung damage and death. We discovered that T cells of severe COVID-19 patients have an increased expression of Kv1.3 channels and that dexamethasone’s beneficial effects in COVID-19 can be in part ascribed to its ability to suppress T cell function via Kv1.3 channel inhibition. These studies emphasize the therapeutic potentials of ion channel blockers in autoimmunity and COVID-19.

3. Development of nanoparticle-based targeted therapy in autoimmunity and cancer. Our ultimate goal is to develop new therapeutics that suppress the activity of T cells in autoimmunity and increase the activity of T cells in cancer. To this end, we have developed a novel therapy for SLE that selectively inhibits memory T cells by knock-down of Kv1.3 channels. We have fabricated functionalized lipid nanovesicles for siRNA delivery. We showed that these nanoparticles effectively prevented the development of lupus nephritis in a humanized mouse model of the disease. We are now applying a similar approach to cancer with the fabrication of lipid nanovesicles for mRNA delivery in adaptive immune cells that can block the immune suppressive effects of the TME via ion channel upregulation.

Steven Crone, PhD.

Maria F. Czyzyk-Krzeska, MD, PhD.

Senad Divanovic, PhD

Yanbo Fan, MD,PhD

John Hogenesch, PhD

Christy K. Holland, PhD.

David Y. Hui, PhD

Theodosia Kalfa, MD, PhD

Jennifer Kaplan, MD, MS

Ian Lewkowich, PhD

Sookkyung Lim, PhD

Richard Lu , PhD

Professor
Department of Pediatrics

Children's Hospital
3333 Burnet Avenue
Office phone 513-636-7684
richard.lu@cchmc.org

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Description of Research:

Recent studies indicate a convergence between neural developmental processes, neurological disorders and brain tumorigenesis whereby insight into one yields insight into the others. We are interested in understanding how distinct glial cell types (e.g., myelinating oligodendrocytes) and their stem / progenitor cells contribute to neurological diseases and how dysregulated developmental programs play a role in tumorigenesis both in the central (CNS) and peripheral (PNS) nervous systems.

A major focus of our lab is to elucidate the transcriptional, posttranscriptional, epigenetic, and signaling networks that govern development, remyelination, and tumor formation in the CNS and PNS. We have established a series of in vitro and in vivo animal models to understand the mechanisms underlying myelinogenesis and neurodegenerative diseases such as multiple sclerosis and autism spectrum disorder, as well as brain tumorigenesis by using endogenous and patient-derived brain or neural tumor models that recapitulate histological and molecular features of human tumors.

We use cutting-edge molecular and cellular approaches (e.g., single-cell multi-omics, functional genomics, and spatial transcriptomics) to dissect how the genetic, epigenetic, and microenvironment controls brain or neural cancer development, recurrence, and metastasis. Our cross-species genomic analyses of human tumors and developing brain tissue at the single cell resolution coupled with genetic mouse modeling have identified a set of glial progenitor-like cells (e.g., Olig2+ pri-OPCs) and “stem-like’ cells (e.g., transitional cerebellar progenitors) as key in the formation of malignant gliomas and medulloblastoma, respectively, pointing to specific cell lineages as the origin of distinct brain tumors, and potential lineage-specific vulnerabilities for targeting distinct subtypes of brain tumors. We are also investigating the tumor microenvironment control of cancer stem cell fitness, tumor recurrence and metastasis by using lineage-traceable model systems for developing effective immunotherapy.

Current projects in Lu Lab aim to:

Leverage cutting-edge genomic and multi-omics approaches to dissect the brain tumor cells of origin and underlying molecular and signaling pathways that are hijacked and altered during the evolution of brain cancers including glioblastoma, medulloblastoma, ependymoma, and diffuse midline gliomas (DMG / DIPG) (Luo et al., Nature, 2022; Hu et al., Nature Cell Biology, 2023; Weng et al., Cell Stem Cell, 2019; Zhang et al., Cancer Cell, 2019; Lu et al., Cancer Cell, 2016, He et al., Nature medicine, 2014).
Define transcriptional, signaling, and epigenetic control of myelination and functional nerve regeneration by using in vitro primary neural cell culture, genetically-engineered mice, and pharmacogenomic approaches (Yu et al., Cell, 2013; Wang, et al., Science Advances, 2020; He et al., Nature medicine, 2018; Zhao et al., Dev Cell 2018; He et al., Neuron, 2017; Wang et al., Dev Cell2017; He et al., Nature Neuroscience, 2016).
Dissect molecular and signaling mechanisms that control Schwann cell myelination in the PNS and the malignant transformation of peripheral nerve sheath tumors (MPNST) by defining the tumor stem-like subpopulation, tumor cell–state evolution and heterogeneity and their regulatory circuitries during NF-to-MPNST transformation (Wu, et al., Science Advances, 2022; Wu et al., Cancer Cell, 2018; Deng et al., Nature communications, 2017; Wu et al., Nature Neuroscience, 2016).

Our research goals comprise dissecting the etiological mechanisms of these neurological diseases and cancers to develop effective therapies respectively through promoting myelin repair and functional nerve regeneration or blocking brain tumorigenesis and recurrence.

Mario Medvedovic , PhD

Tesfaye Mersha, PhD

William Miller, PhD

Emily R. Miraldi , PhD

Tomoyuki Mizuno, PhD

Jeffery Molkentin, PhD

Takahisa Nakamura, PhD

Anjaparavanda Naren , PhD

Daria Narmoneva , PhD

David Plas, PhD

Timothy A. Pritts, MD

Mattia Quattrocelli, PhD

Anca L. Ralescu, PhD

Laura Ramsey, PhD

Jack Rubinstein, MD

Sakthivel Sadayappan, PhD, MBA

Nathan Salomonis, PhD

Vinita Takiar, MD, PhD

Professor
Department of Radiation Oncology

UC Barrett Cancer Center
3151 Bellevue Avenue
Cincinnati, OH 45219
Office Phone: 513-584-5668
vinita.takiar@uchealth.com

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Description of Research:

The Takiar and Wise-Draper co-led laboratory is interested in mechanisms of resistance to various anti-cancer therapy. Dr. Wise-Draper is a medical oncologist focused on experimental therapeutics for the treatment of head and neck cancer and other solid tumor malignancies. Dr. Takiar is a radiation oncologist with a clinical focus on treating patients with head and neck cancer. As such, the Takiar & Wise-Draper group uses head and neck cancer as a model system to better understand how tumors may respond to treatment including chemotherapy,immunotherapy, and radiation therapy, and the

mechanisms by which tumors recur despite aggressive treatment. The laboratory also participates in the translational elements of clinical trials in order to better understand the basic biology behind the outcomes being observed in the clinic.

The overall goal of the laboratory is to better understand how tumor cells evade or resist cell death by anti-cancer therapy. If these mechanisms were better understood, then potentially clinical treatment could be better tailored to each patient.

One focus of the laboratory is on identifying mechanisms of adaptive resistance to radiation therapy. For this project, we use Reverse Phase Protein Microarray Analysis (RPPA) as well as cellular and mouse models to try and replicate the human host. Select therapies are then tested alone and in combination with ionizing radiation in a strategic manner to identify new combinations of treatment that may be more effective than those currently available.

Another focus of the laboratory is on better understanding the mechanisms underlying resistance to immunotherapy, including T-cell dysfunction, and the potential role of NK cells and the microenvironment. Currently, immunotherapy is indicated for patients in the recurrent or metastatic setting for head and neck cancer, and although those who respond to treatment have terrific outcomes, the majority of patients do not respond. The goals of this project are to be able to better identify patients most likely to respond to treatment and to understand how to turn a non-responder into a responder to potentially design subsequent human trials that will improve immunotherapy effectiveness.

Zachary L Taylor, PhD, MS

Tom B. Thompson, PhD

Lubov Timchenko, PhD

Susan E. Waltz, PhD

Professor
Department of Cancer & Cell Biology

Vontz Center 2328
Office Phone: 513-558-8675
waltzse@ucmail.uc.edu

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Description of Research:

The Waltz laboratory is interested in the molecular mechanisms by which cell-surface receptor tyrosine kinases and growth factors control human disease processes, with a special emphasis on mechanisms regulating cancer growth and metastasis, and inflammation. The Waltz group has made several seminal discoveries related to the Ron receptor tyrosine kinase in both breast and prostate cancers. In particular, the laboratory has shown that Ron overexpression specific to the breast epithelium is sufficient to induce aggressive breast cancers that are highly metastatic. In addition, the Waltz group has found that Ron is an important contributing factor controlling the growth of prostate cancers through the regulation of tumor angiogenesis (blood vessel formation). The immediate goals for these projects are to understand the physiological signaling pathways that control the aggressive tumor phenotype downstream of Ron signaling. Future studies will involve the utilization of in vivo gene-targeted murine models to study disease progression as well as the isolation and analysis of primary epithelial and stromal cells from the breast and prostate environments. In addition, the laboratory plans to use orthotopic transplantation of gene-modified cell lines into syngeneic models to explore these signaling pathways in detail.

With respect to control of cellular inflammation, the Waltz laboratory has also shown that Ron is expressed on select macrophage populations, and that signaling through this receptor negatively regulates the balance of cytokine and chemokine production during acute tissue injury in vivo. This critical balance of immune mediators is essential to control the body's response to injury, wounding, and infection. To analyze the mechanisms responsible for the Ron-dependent regulation of cytokine/chemokine production, the laboratory utilizes co-culture systems composed of primary tissue macrophages and epithelial cells from select gene knockout animals to dissect the role of macrophages in tissue injury.

The overall goal of the Waltz laboratory is to examine the Ron signaling pathway as a novel therapeutic target in the regulation of a variety of human diseases.

Yigang Wang, MD, PhD

Professor
Department of Pathology & Laboratory Med

Cardiovascular Research Center 1933
COM Pathology Wang Lab - 0529

Office Phone: 513-558-5798
wanyy@ucmail.uc.edu

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Description of Research:

Dr. Wang's research over the past two decades has focused on cardiovascular pathophysiology and therapies, with three primary areas of concentration: 1) studying the impact of various additive agents in cardioplegic solutions on functional cardiac restoration, 2) investigating ischemic preconditioning as a protective mechanism against ischemia/reperfusion injury, including its molecular mechanisms and signaling pathways, and 3) advancing progenitor/stem cell-based therapy for treating myocardial infarction.

Currently, Dr. Wang's research team delves into progenitor/stem cell biology, with a particular emphasis on pluripotency, differentiation, proliferation, and survival. Their aim is to enhance the regenerative potential of adult heart tissue following myocardial infarction (MI). Through innovative CRISPR-induced cell manipulation techniques, they have successfully generated cardiovascular progenitor cells (CPCs) exhibiting clonality, self-renewal, and cardiac tri-potentiality. These CPCs have shown promising results in improving heart function and reducing scar formation in MI mice upon transplantation. Dr. Wang's team is also developing a viral or non-viral CRISPR approach to activate endogenous genes for CPC generation from fibroblasts, with a focus on identifying long non-coding RNAs (lncRNAs) crucial for epigenetic remodeling during cell reprogramming. Additionally, their research explores the roles of transcription factors, microRNAs, and growth factors in optimizing conditions for cardiomyocyte regeneration. Notably, they have identified microRNA-128 as a pivotal regulator of cardiomyocyte proliferation, offering a novel therapeutic avenue for heart repair. Dr. Wang's research has gained notable recognition in esteemed cardiovascular journals, underscoring their substantial expertise in cardiovascular research and previous experience as a cardiovascular and thoracic surgeon. This wealth of knowledge, combined with adeptness in both animal models and human surgeries, uniquely equips Dr. Wang to pioneer advancements in myocardial repair strategies through progenitor/stem cell-based therapy in ischemic environments.

Russell Ware, MD, PhD

Joshua Waxman, PhD

Matthew Weirauch, PhD

Jeffrey A. Whitsett, MD

Professor
Department of Pediatrics - Pulmonary Biology

Children's Hospital Building R
Office Phone: 513-636-7665
jeffrey.whitsett@cchmc.org

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Description of Research:

Dr. Whitsett is internationally known for his research in pulmonary medicine and his clinical expertise in neonatology. Dr. Whitsett has made groundbreaking contributions to pulmonary medicine and biology in his studies of the surfactant proteins A, B, C, and D, cloning their genes and clarifying their roles in lung development and function. Throughout his career, Dr. Whitsett has transitioned from molecular biology to animal models and then to the diagnosis and therapy of human disease. Notably, he has played a critical role in making surfactant protein replacement routine in the treatment of immature lungs and respiratory distress syndrome in premature infants. Notably, his laboratory has contributed to the identification of a number of genes critical for lung formation and function and shown that mutations in genes regulating surfactant homeostasis are responsible for acute and chronic lung disease in infants and adults. Dr. Whitsett is the author of over 600 basic science and clinical literature papers.

Our laboratory discovered surfactant proteins B and C, cloned the genes encoding the surfactant proteins A, B, C, and D, Scgb1a1, TTF-1, and others, and utilized transgenic mouse models to delete and mutate these genes in transgenic mice. We identified transcriptional networks regulating lung morphogenesis and perinatal lung maturation contributing to the understanding of the roles of TTF-1, CEBPα, SOX2, SOX17, FOXA1, FOXA2, FOXA3, FOXF1, SPDEF, KLF5, CDC42, GATA6 and Hippo/YAP using both in vitro and in vivo methods. We identified multiple transcription factors regulating goblet cell differentiation in airway epithelial cells, including novel roles for SPDEF and FOXA3 in airway goblet cells controlling innate immunity in the lung. We produced transgenic mouse models for conditional deletion and expression of genes involved in lung development, disease, and repair, including mouse models of pulmonary adenocarcinoma and pulmonary alveolar proteinosis (PAP). We utilized RNA-Seq, microarray, Chip-Seq, and ATAC-Seq in the application of Next-Gen sequencing and bioinformatics to identify and understand the cellular and molecular networks involved in the regulation of lung development and disease using clinical samples, in vitro and in vivo models.

David F. Wieczorek, PhD

Jane J. Yu, PhD

Jun-Ming Zhang, MD, MSc

Professor
Department of Anesthesiology

Medical Sciences Building 3413
Office Phone: 513-558-2427
zhangj4@ucmail.uc.edu

Publications
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Description of Research:

Chronic pain conditions such as neuropathic pain are very common and can last a lifetime, persisting long after the initial damage to the nerve has healed. Chronic pain conditions involve complex, orchestrated changes in the sensory neurons and their synaptic targets. These changes include abnormal electrical activity, alterations in ion channels and transmitters, and sensitization of the pain pathways in the spinal cord and brain. We are currently investigating the role of cytokines in pain. We have developed new animal models involving compression and/or inflammation of the sensory ganglia. These models are particularly relevant to understanding low back pain. We have found that several inflammatory cytokines are upregulated in these models, with a time course that parallels the development of pain behaviors. Our aim is to understand the possible causal roles of these cytokines in abnormal pain states, with the ultimate goal of identifying new therapeutic targets for chronic pain. We use a number of techniques, including electrophysiology, animal behavior, microscopy, and biochemical and molecular methods. In a related project, we are also investigating the role and causes of the abnormal sympathetic sprouting into the sensory ganglia that exacerbates many chronic pain states and how sympathetic regulate local immune/inflammatory responses. Recently, we have started several new projects: 1) determine how microvascular responses in the dorsal root ganglia triggers neuropathic spontaneous pain; 2) relationship between nerve injury initiated regeneration and the persistence of neuropathic pain; 3) how steroid receptors change under pathological conditions and how such changes may affect therapeutic efficacy of steroids used for managing inflammatory pain conditions. Lastly, we have initiated several clinical studies to translate preclinical findings to clinical practice. Specifically, we are interested in whether extended nerve block provides additional benefit for patients with traumatic injury in lowing the risk of chronic pain; and how to improve efficacy of epidural steroids for managing low back pain.

Basilia Zingarelli, MD, PhD

Professor
Department of Pediatrics - Critical Care

Children's Hospital Building R 033
Office Phone: 513-636-8704
basilia.zingarelli@cchmc.org

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Description of 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. 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.

PhD Research Mentors

Current projects in Lu Lab aim to:

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