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Boettiger, Charlotte
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Publications
PHD PROGRAM
Neuroscience

My lab uses a cognitive neuroscience approach to understand the neurobiology of drug addiction in humans. The tools we use include fMRI, cognitive testing, physiological monitoring, pharmacology, and genetic testing. We specifically seek to determine 1) how the brain learns new stimulus-response associations and replaces learned associations, 2) the neurobiological mechanisms underlying the tendency to select immediate over delayed rewards, and 3) the neural bases of addiction-related attentional bias.


How do networks of cells synchronize behaviors across differing spatial and temporal scales? This fundamental aspect of cellular dynamics is broadly relevant to understanding many biological systems in which the coherence of electrical or chemical signals is required for multicellular patterning or organ function. Our group’s primary research interests are related to understanding the cellular and microenvironmental conditions that are required to support the biorhythmic behavior of the system of cells that natively control heart rate, cardiac pacemaker cells. We utilize a variety of techniques including computational modeling, next generation sequencing, in vivo genetic manipulation, super-resolution imaging, and direct physiological recording to investigate the developmental processes that assemble the hearts pacemaking complex. The ultimate goals of these studies is to determine how the pacemaker cell lineage is patterned in the embryo, build strategies towards fabricating this cell type for therapeutic purposes, and identify vulnerabilities that may lead to pacemaker cell pathologies in humans.


Research in the Brouwer laboratory is focused on: (1) hepatic transport of xenobiotics, including mechanisms of uptake, translocation, and biliary excretion; (2) development/refinement of in vitro model systems to predict in vivo hepatobiliary disposition, drug interactions, and hepatotoxicity; (3) influence of disease (e.g., NASH, kidney disease) on hepatobiliary drug disposition; and (4) pharmacokinetics.


The Button lab in the Department of Biochemistry and Biophysics is part of the Marsico Lung Institute. Our lab is actively involved in projects that are designed to define the pathogenesis of muco-obstructive pulmonary disorders and to identify therapies that could be used to improve the quality of life in persons afflicted by these diseases. In particular, our research works to understand the biochemical and biophysical properties of mucin biopolymers, which give airway mucus its characteristic gel-like properties, and how they are altered in diseases such as Asthma, COPD, and cystic fibrosis.


The immune system of severely burned patients becomes extremely suppressed after injury. An overwhelming number of patients die from wound infection and sepsis. However, we are unable to graft these patients with skin from other donors as their immune system is still able to reject the graft efficiently. Our inability to cover the wound site leaves the patients further open to bacterial and fungal infections. Our laboratory investigates the translational immune mechanisms for these devastating consequences of burn within mouse models and burn patients. Focuses in the lab include 1) investigation of innate molecule control of both the innate and adaptive immune systems after burn injury, 2) Role of innate signaling to Damage Associated Molecular Patterns in Immune Dysfunction after burn / inhalational injury,focusing on mTOR-mediated Immunomodulation 3) Using NRF2/KEAP1-Targeted Therapy to Prevent Pneumonitis and Immune Dysfunction After Radiation or Combined Burn-Radiation Injury and 4) Investigating sex-specific disparities in Immune Dysfunction after trauma / transplantation. ​


Carelli, Regina M.
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Publications
PHD PROGRAM
Neuroscience

Research in the Carelli laboratory is in the area of behavioral neuroscience. Our studies focus on the neurobiological basis of motivated behaviors, including drug addiction. Electrophysiology and electrochemistry procedures are used during behavior to examine the role of the brain ‘reward’ circuit in natural (e.g., food) versus drug (e.g., cocaine) reward. Studies incorporate classical and operant conditioning procedures to study the role of the nucleus accumbens (and dopamine) and associated brain regions in learning and memory, as they relate to motivated behaviors.


Gene targeting and state-of-the-art phenotyping methods are used to elucidate the reproductive and cardiovascular roles of the adrenomedullin system and to characterize the novel GPCR-signaling mechanism of Adm’s receptor and RAMP’s.


Christoffel, Dan
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Publications
PHD PROGRAM
Neuroscience

Dr. Christoffel aims to understand how chronic exposure to particular stimuli (i.e. stress, food, drugs) alters the functioning of specific neural circuits and investigates the mechanisms that regulate these experience-dependent changes. Current studies focus on 1) how experience-dependent plasticity in the nucleus accumbens regulates reward processing, with a focus on the consumption of palatable foods and stress modulation of food intake, and 2) examine the regulatory role of neuromodulators in hedonic feeding.

The ultimate goal of the Christoffel Lab’s research is to understand how adaptive changes in brain function occur and how this can lead to the development of psychiatric disorders. We employ cutting-edge technologies to understand the complex interactions of multiple neural systems that allow us to adapt to our environment and regulate motivated behavior.


My lab in the UNC CEMALB uses translational in vitro and clinical in vivo approaches to investigate how inhaled xenobiotics modify respiratory innate immune responses in people with and without existing lung disease. A central component of my research is the integration of biomedical engineering, additive manufacturing, and advanced cell culture methods to evaluate the health effects of new and emerging tobacco products such as e-cigarettes. I believe the best research is achieved through collaboration across disciplines and welcome interested trainees to contact me to learn more about my lab.


Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes.


The Cohen Lab investigates how functional brain networks in humans interact and reconfigure when confronted with changing cognitive demands, when experiencing transformations across development, and when facing disruptions in healthy functioning due to disease. We are also interested in how this neural flexibility contributes to flexibility in control and the ability to learn, as well as the consequences of dysfunction in this flexibility. We use behavioral, neuroimaging, and clinical approaches taken from neuroscience, psychology, and mathematics to address our research questions.


As the Director of the UNC Kidney Center, the scope of Dr. Falk’s research interests spans many disciplines, including molecular biology, immunology, genetics, pathology, cell biology, protein chemistry, epidemiology, pharmacokinetics and biostatistics. Dr. Falk is recognized world wide as a leader in research on kidney diseases related to autoimmune responses. He works closely with the basic research scientists within the UNC Kidney Center, including Dr. Gloria Preston, thus this research program provides an environment for Translational Research within the UNC Kidney Center.


Air pollution exposure is associated with increased hospital visits and mortality, and is a major area of research for the United States Environmental Protection Agency.  The primary research interest of my laboratory is the examination of the effects and mechanisms of air pollutants in the environment on normal cardiopulmonary function (cardiac toxicology), particularly in models of cardiovascular disease, using state-of-the-art targeted and high throughput methods. Research findings are often used to inform environmental public health and contribute to the refinement of the US EPA’s National Ambient Air Quality Standards for specific air pollutants set to limit their health impact.


Our goal is to revolutionize the treatment of psychiatric and neurological illness by developing novel brain stimulation paradigms. We identify and target network dynamics of physiological and pathological brain function. We combine computational modeling, optogenetics, in vitro and in vivo electrophysiology in animal models and humans, control engineering, and clinical trials. We strive to make our laboratory a productive, collaborative, and happy workplace.


Our lab is studying the role of mitogen and stress-activated protein kinases to regulate key aspects of cell metabolism. We are also studying signalling by tyrosine kinases in response to toxicological agents or cell stress.


My group develops and deploys computational tools to predict physiological function and dysfunction. We are interested in a range of applications in medicine and biology, but our primary focus is the cardiovascular system. My group is actively developing fluid-structure interaction (FSI) models of the heart, arteries, and veins, and of cardiovascular medical devices, including bioprosthetic heart valves, ventricular assist devices, and inferior vena cava filters. We are also validating these models using in vitro and in vivo approaches. We also model cardiac electrophysiology and electro-mechanical coupling, with a focus on atrial fibrillation (AF), and aim to develop mechanistically detailed descriptions of thrombosis in AF. This work is carried out in collaboration with clinicians, engineers, computer and computational scientists, and mathematical scientists in academia, industry, and regulatory agencies.


The human placenta is the first organ to develop after fertilization and is the least studied! We hope to change this by using a multidisciplinary approach. From iPSC-derived trophoblasts in culture to mouse models and human placenta tissue, the Placental Cell Biology Group at NIEHS answers fundamental questions about placenta cell and developmental biology. Our lab uses a range of microscopy (cryo-EM, fluorescence), recombinant protein production, and -omics techniques. The goal of our research is to understand how autophagy controls placenta development, differentiation, and function.


The Hantman Lab is interested in how functions emerge from network activity in the nervous system. Particularly, we study how the nervous system generates patterns of activity that control our bodies in the world. Our approach combines genetics, anatomy, physiology, perturbations, and a dynamical systems approach.


Research in my laboratory focuses on the effects of air pollution and other environmental pollutants on the cardiovascular and respiratory systems. We use both traditional as well as novel physiological approaches (radiotelemetry, HF echocardiography, physiological challenge testing) to determine not only the short-term effects of exposure, but also the long-term consequences on health, particularly in the development of chronic diseases (e.g. heart disease). Rodent models are used to study the effects of real-world air pollution concentrations on the central and local neural controls of the cardiovascular and respiratory systems that render a host susceptible to adverse health events. Newer exciting research is focused on public health aspects such as nutrition (e.g. vitamin deficiencies) and non-environmental stressors (e.g. noise, climate change, social disruption) as modifiers of air pollution health effects. These studies examine the epigenetic changes that occur in early life or during development that result in physiological effects and future susceptibility.


Hedrick, Tyson
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Publications
PHD PROGRAM
Biology

Research in my laboratory focuses on how animals produce and control movement, with a particular interest in animal flight.  We use both computational and experimental techniques to examine how organismal components such as the neuromuscular and neurosensory systems interact with the external environment via mechanics and aerodynamics to produce movement that is both accurate and robust.  Keywords: biomechanics, flight, avian, insect, neural control, muscle, locomotion, computational modeling.


My research interests involve the structure of inhibitory neuronal networks and how these networks change to produce adverse behavioral outcomes. My main interest is how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) regulates neuronal networks via both synaptic and extrasynaptic forms of inhibition and how alterations in inhibitory networks contribute to clinical conditions such as alcohol use disorder, nicotine, addiction, or stress. My work has focused primarily on three brain regions: the nucleus tractus solitaries (NTS), central and basolateral amygdala, and ventral tegmental area. In each of these areas I have identified local inhibitory networks that control overall excitability and that are dysregulated by exposure to acute and or chronic exposure to alcohol or nicotine.


Flexibility of the brain allows the same sensory cue to have very different meaning to the animal depending on past experience (i.e. learning and memory) or current context. Our goal is to understand this process at the levels of synaptic plasticity, neural circuit and behavior. Our model system is a simple brain of the fruit fly, Drosophila. We employ in vivo electrophysiology and two-photon calcium imaging together with genetic circuit manipulation. Taking advantage of this unique combination, we aim to find important circuit principles that are shared with vertebrate systems.

 


Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.


Hursting, Stephen D
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Publications
PHD PROGRAM
Nutrition

Dr. Hursting’s lab focuses on the molecular and metabolic mechanisms underlying nutrition and  cancer associations, particularly the impact of obesity and energy balance modulation (eg, calorie restriction, exercise) on cancer development or responses to chemotherapy. Primarily using genetically engineered mouse models of pancreatic, colon and breast cancer, Dr. Hursting has identified the IGF-1/Akt/mTOR and NF-kB signaling pathways as key targets for breaking the obesity- cancer link.  He has also established in several preclinical models of pancreatic and breast cancer that obesity impacts the response to various forms of chemotherapy.  In addition, the Hursting lab is involved in several translational research collaborations linking mouse model studies with clinical trials, and his group has expertise in measuring metabolic hormones, growth factors, inflammatory cytokines and chemokines in serum and tissue from rodents and humans.


Our lab uses cell culture and animal models to define the mechanisms that lead to heart failure and to identify novel approaches to its treatment.  We are particularly interested in the roles of inflammation and cardiomyocyte metabolism in the pathobiology of the failing heart. Ongoing projects focus on (1) the cardioprotective role of the alpha-1A adrenergic receptor; (2) transcriptional regulation by the nuclear receptor ROR-alpha; (3) cardiotoxicity of antineoplastic kinase inhibitors.


Emotional behavior is regulated by a host of chemicals, including neurotransmitters and neuromodulators, acting on specific circuits within the brain. There is strong evidence for the existence of both endogenous stress and anti-stress systems. Chronic exposure to drugs of abuse and stress are hypothesized to modulate the relative balance of activity of these systems within key circuitry in the brain leading to dysregulated emotional behavior. One of the primary focuses of the Kash lab is to understand how chronic drugs of abuse and stress alter neuronal function, focusing on these stress and anti-stress systems in brain circuitry important for anxiety-like behavior. In particular, we are interested in defining alterations in synaptic function, modulation and plasticity using a combination of whole-cell patch-clamp physiology, biochemistry and mouse models.  Current projects are focused on the role of a unique population of dopamine neurons in alcoholism and anxiety.


Kato, Hiroyuki
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Publications
PHD PROGRAM
Neuroscience
RESEARCH INTEREST
Behavior, Neurobiology, Physiology

Our primary goal is to identify how our brain processes sound inputs to detect complex patterns, such as our language. Using mouse auditory cortex as a model system, we combine multiple cutting-edge techniques (e.g. in vivo whole-cell recording, two-photon calcium imaging, and optogenetics) in behaving animals to dissect the circuits that connect vocal inputs to behavioral outputs. Findings in the simple mouse cortex should provide a first step towards the ultimate understanding of the complex human brain circuits that enable verbal communication, and how they fail in psychiatric disorders.


Endothelial cells, which comprise the innermost wall of all blood vessels, are involved in a broad range of metabolic and cardiovascular diseases that represent a global challenge with high morbidity. Endothelial cell metabolism is an active process, and altered endothelial metabolism drive disease progression. The research in my lab focuses on the molecular mechanisms of endothelial cell metabolism and how they affect cardiovascular and metabolic diseases.


Madden, Michael C.
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Publications
PHD PROGRAM
Toxicology

Exposure to ambient air particulate matter  has been associated with increased human deaths and cardiopulmonary morbidity, such as lung infections and increased asthma symptoms.  I am investigating some types of PM and associated gases  that may be associated with those health effects so  to better regulate or manage the sources of the airborne particles which are identified as playing a role in the adverse health outcomes. I am currently focusing on the effects of diesel exhaust using a variety of approaches ranging from exposing cultured human lung and vascular cells to the exhaust, to studying responses of humans exposed out in traffic.  I am currently designing and implementing testing strategies to assess the toxicity of the future types of vehicular emissions. Additionally some of my research effort attempts to identify what populations are more sensitive to the effects of air pollutants, and the genetic, diet, and environmental reasons behind the increased sensitivity.


Our fundamental interest is in how the nervous system processes sensory information. We have been studying these problems using in vitro preparations that allow us to examine how single cells in the auditory cortex and auditory brainstem operate to integrate synaptic input, generate precisely timed action potentials, and adapt to changes in sensory input produced by hearing loss.  This has involved investigations into the kinds of ion channels expressed in particular subsets of cells, determination of the kinetics and voltage dependence of those channels, studies of synaptic transmission, and the generation of computational models that reflect our current understanding of how these cells operate and produce responses to acoustic stimuli.  A longstanding interest has been in the types of processing that take place in the elaborate network of cells in cerebral cortex. The structure and function of neurons in the auditory cortex depends extensively on sensory experience. We are now studying the functional spatial organization of auditory cortical neural networks at the level of connections between classes individual cells, using optical methods in normal mice and mice with noise-induced hearing loss.


We are a biological oceanography lab that performs inquiry-based science by combining physiological and molecular approaches in laboratory isolates and natural communities to investigate how marine microorganisms are affected by their environment and in turn, influence ocean biogeochemistry and ecosystem dynamics. Particular interests include studying trace metals, such as iron, that are essential for the nutrition of phytoplankton and predicting the effects of future climate changes on phytoplankton distribution and abundance.  We implement the use of environmental genomic approaches (e.g. RNA-seq) to ascertain the ways in which marine microbes have adapted and acclimate to varying environmental conditions.


The McCauley Lab is interested in how the food we eat changes our physiology. Rare, nutrient sensing cells in the intestine called enteroendocrine cells secrete hormones in response to environmental cues that orchestrate systemic metabolism. How these cells regulate their neighbors in the gut is not well understood. We use mouse models which lack enteroendocrine cells and human pluripotent stem cell derived intestinal organoids to discover new roles for these master metabolic cells in the regulation of intestinal physiology and function. Enteroendocrine cells are dysregulated in inflammatory bowel disease, type 2 diabetes, and obesity, and loss of enteroendocrine cells results in malabsorptive diarrhea with poor survival. Our research has the potential to improve human health for a wide segment of the global population.


Research in the McElligott lab focuses on the circuits and plasticity that underlie the development and manifestation of psychiatric illness, specifically disorders on the affective spectrum including alcohol use disorders, drug abuse and anxiety disorders. The lab has expertise in studying neurotransmission from the level of signaling in individual cells through behavior utilizing a variety of techniques including: whole-cell electrophysiology, in vivo and ex vivo fast-scan cyclic voltammetry (FSCV), circuit manipulations (optogenetics, chemogenetics, caspase ablation), and behavioral assays.  There are several ongoing projects in the lab. One area we are focused on explores the role of neurons in the central nucleus of the amygdala (CeA) that express the neuropeptide neurotensin and the role these neurons play in alcohol related phenotypes. Additionally we are interested in exploring how norepinephrine modulates neurotransmission within the brain and how the norepinephrine system itself is modulated in models of substance abuse and post-traumatic stress. Beyond these studies, we are actively engaged in several other collaborative projects with other labs at UNC, as well as around the world.


Our research interests focus on investigating the reparative processes critical to the resolution of acute lung injury. Acute events such as pneumonia, inhalational injury, trauma, or sepsis often damage the lung, impeding its primary function, gas exchange. The clinical syndrome these events can lead to is termed Acute Respiratory Distress Syndrome (ARDS). ARDS is a common pulmonary disease often seen and treated in intensive care units. Despite decades of research into the pathogenesis underlying the development of ARDS, mortality remains high. Our laboratory has built upon exciting observations by our group and others on the importance of how the lung repairs after injury. One type of white blood cell, the Foxp3+ regulatory T cell (Treg), appears essential in resolving ARDS in experimental models of lung injury–through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. Importantly, Tregs are present in patients with ARDS, and our lab has found that subsets of Tregs may play a role in recovery from ARDS.


Modern Technologies from next-gen sequencing to high resolution imaging have advanced our knowledge of kidney development, function, and disease. We are among the pioneers utilizing techniques such as CHIP-seq, RNA-seq, modern genome editing, and imaging to understand how regulatory programs control progenitor populations during kidney development. Our goal is to understand how these programs contribute to progenitor specification and maintenance, and how they are altered during disease and aging. Our ultimate goal is translational applications of our research to develop new therapeutics and regenerative strategies.


My lab is driven to understand the neuronal pathologies underlying neurodevelopmental disorders, and to use this information to identify novel therapeutics.  We focus our research on monogenic autism spectrum disorders, including Angelman, Rett, and Pitt-Hopkins syndromes.  We employ a diverse number of techniques including: electrophysiology, molecular biology, biochemistry, mouse engineering, and in vivo imaging.


My laboratory, located in the Cystic Fibrosis/Pulmonary Research and Treatment Center in the Thurston-Bowles building at UNC, is interested in how respiratory viruses infect the airway epithelium of the conducting airways of the human lung.


My laboratory research is focused on basic cell biology questions as they apply to clinical lung disease problems. Our main work recently has been contributing to the Cystic Fibrosis (CF) Foundtation Stem Cell Consortium, with a focus on developing cell and gene editing therapies for CF. I contribute to UNC team science efforts on cystic fibrosis, aerodigestive cancers, emerging infectious diseases and inhalation toxicology hazards. I direct a highly respected tissue procurement and cell culture Core providing primary human lung cells and other resources locally, nationally and internationally. I co-direct the Respiratory Block in the UNC Translational Educational Curriculum for medical students and also teach in several graduate level courses.


Reissner, Kathryn
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Publications
PHD PROGRAM
Neuroscience

Research in our lab is focused on understanding how cocaine abuse affects glial cell physiology, in particular neuron-astrocyte communication.  We utilize the rat cocaine self-administration/reinstatement model, which allows us to test hypotheses regarding not only how chronic cocaine use affects properties of astrocytes and the tripartite synapse, but also how compounds affecting glial cells may influence synaptic processing within the brain’s reward neurocircuitry and behavioral measures of drug seeking.


The Robinson lab currently explores the neurodynamics of reinforcement pathways in the brain by using state-of-the-art, in vivo recording techniques in freely moving rats. Our goal is to understand the interplay of mesostriatal, mesocortical and corticostriatal circuits that underlie action selection, both in the context of normal development and function, and in the context of psychiatric disorders that involve maladaptive behavior, such as alcohol use disorder, adolescent vulnerability to drug use and addiction, cocaine-induced maternal neglect and binge-eating disorders.


Pain is a complex experience with sensory and emotional components. While acute pain is essential for survival, chronic pain is a debilitating disease accompanied by persistent unpleasant emotions. Efficient medications against chronic pain are lacking, and the absence of alternative to opioid analgesics has triggered the current Opioid Epidemic. Our lab studies how our nervous system generates pain perception, at the genetic, molecular, cellular, neural circuit, and behavioral levels. We also seek to understand how opioids alter activity in neural circuits to produce analgesia, but also side effects such as tolerance, addiction and respiratory depression. To this aim, we investigate the localization, trafficking and signaling properties of opioid receptors in neurons. These studies clarify pain and opioid mechanisms for identifying novel non-addictive drug targets to treat pain and strategies to dissociate opioid analgesia from deleterious effects.


The Serody laboratory focuses on tumor and transplant immunology studies using both animal models and translational work with clinical samples. We have performed pioneering work in both of these areas. Our laboratory was the first to describe a role for migratory proteins in the biology of acute GVHD. We were the first group to use eGFP transgenic mice generated in part by our group to track the migration of donor cells after transplant. This work showed a critical role for lymphoid tissue in the activation of donor T cells. Most recently we have been the first group to demonstrate the absence of ILC2 cells in the GI tract after all types of transplant and we have generated novel studies into the ILC2 niche in the bone marrow. For our tumor work we were one of the first groups to use genomic evaluations of the tumor microenvironment to characterize the immune response in cancer models. We were the first group to demonstrate how to enhance checkpoint inhibitor therapy in triple negative breast cancer models and have been one of the leading groups in performing genomic evaluations using TCGA data. Finally, we are one of the leading groups in the world characterizing the role of B cells in the anti-tumor immune response.


Dr. Shih is the Director of Small Animal Magnetic Resonance Imaging (MRI) at the Biomedical Research Imaging Center. His lab has implemented multi-model MRI techniques at high magnetic field to measure cerebral blood oxygenation, blood flow, blood volume, and oxygen metabolism changes in preclinical animal models. Dr. Shih’s lab is also developing simultaneous functional MRI (fMRI) and electrophysiology recording techniques at high spatial resolution to elucidate the pathophysiological mechanisms of neurovascular diseases. They will apply these techniques to (i) explore/validate functional connectivity network and neurovascular coupling in the rodent brain, (ii) study tissue characteristics after stroke, and (iii) investigate deep brain electrical stimulation, optogenetic stimulation, and pharmacogenetic stimulation in normal and Parkinsonian animal models.


Our lab has two areas of interest: the molecular basis of liver diseases and the biochemical mechanisms of disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of our work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.


Styblo, Miroslav
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Publications
PHD PROGRAM
Nutrition, Toxicology
RESEARCH INTEREST
Physiology, Toxicology

Dr. Styblo is a biochemist with background in nutritional biochemistry and biochemical toxicology. His research focuses on topics that require expertise in both nutrition and toxicology and typically involve a translational or interdisciplinary approach. His current research projects examine mechanisms and etiology of diseases associated with exposures to environmental toxins with main focus on cancer and diabetes associated with exposure to arsenic (a common drinking water contaminant), and on the role of diet or specific nutrients in prevention of these diseases.


Tarran, Robert
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Publications
RESEARCH INTEREST
Cell Biology, Pathology, Physiology

A critical component of airways innate defense is the thin liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly. The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas: 1) Regulation of epithelial cell function by the extracellular environment, 2) Gender differences in cystic fibrosis lung disease and 3) The effects of cigarette smoke on epithelial airway ion transport. We utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions.


Thiele, Todd
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Publications
PHD PROGRAM
Neuroscience

My primary research interests are directed at the neurobiology of alcoholism. To study the central mechanisms involved with neurobiological responses to ethanol, I use both genetic and pharmacological manipulations. There are many factors that may cause an individual to progress from a moderate or social drinker to an alcoholic. In addition to environmental influences, there is growing evidence in both the human and animal literature that genetic factors contribute to alcohol abuse. Furthermore, the risk for developing alcoholism is likely not associated with a single gene, but rather with multiple genes that interact with environmental factors to determine susceptibility for uncontrolled drinking. Some of the questions that my laboratory is currently addressing are: 1) Does central neuropeptide Y (NPY) signaling modulate neurobiological responses to ethanol and ethanol consumption, 2) Do melanocortin peptides modulate ethanol intake? and 3) Does cAMP-dependent kinase (PKA) play a role in voluntary ethanol consumption and/or other effects produced by ethanol?


Research in my laboratory focuses on the cardiovascular effects of air pollution and other environmental pollutants in human, animal, and in vitro models, as well as the dietary interventional strategies to mitigate the adverse health effects of air pollution exposure. We are currently conducting two clinical studies to investigate the cardiopulmonary effects of air pollution exposure, and to determine whether dietary omega-3 fatty acids can mitigate the air pollution-induced health effects in human volunteers. These studies provide good training opportunities for students who are interested in training in clinical and translational toxicology research.


My research interests are focused on mechanisms associated with altered innate immune functions, which lead to dysregulated adaptive immunity. Currently my research program has three major arms integrated through with a central philosophy. Specifically, our laboratory focuses on the contribution of epithelial cell biology and signaling to innate and adaptive immune homeostasis and dysfunction. We study the contribution of what I term ‘epithelial cell innate immune (dys)function’ to three major disease conditions: pancreatic cancer, type 1 diabetes (autoimmunity), and periodontal disease (autoinflammation). While appearing to be a diverse research program, we have found that many of the mechanisms and systems in play are surprisingly (or maybe not so surprisingly) similar allowing for rapid translation of our findings. Importantly, previous investigations into the role of epithelial cells in immunobiology have been hindered by a lack of robust primary cell culture techniques, which our laboratory has been able to overcome using both animal and human tissues. Thus, using our novel and unique tools we are able to evaluate our findings in the human conditions, again making translation of our findings that much more feasible. In addition to my primary research objectives, my collaborative research programs, have allowed me to be involved, at some level, in investigating the basic biology of health, multiple autoimmune conditions, autoinflammation, sepsis, and exercise induced inflammation I have been blessed with the opportunities to couple my passions and expertise with that of others to bring together multiple research communities with the goal of advancing human health and hope to be able to continue to do so for years to come.


Social behavior is composed of a variety of distinct forms of interactions and is fundamental to survival. Several neural circuits must act in concert to allow for such complex behavior to occur and perturbations, either genetic and/or environmental, underlie many psychiatric and neurodevelopment disorders. The Walsh lab focuses on gaining an improved understanding of the biological basis of behavior using a multi-level approach to elucidate the molecular and circuit mechanisms underlying motivated social behavior. The goal of our research is to uncover how neural systems govern social interactions and what alterations occur in disease states to inform the development of novel therapeutics or treatment strategies.

One of the major focuses of the Walsh lab is on understanding how genetic mutations, as well as experience, lead to circuit adaptations that govern impaired behavior seen in mouse models of autism spectrum disorders (ASD). Our systems level analysis includes: 1) modeling these disorders with well described genetic markers, 2) defining causal relationships between activity within discrete anatomical structures in the brain that are critical to the physiology of the symptom under investigation (e.g. sociability), 3) performing deep characterization of the physiological profiles of these circuits and using that information to target specific receptors or molecules that may not have been considered for the treatment of specific ASD symptoms.


Watkins, Paul
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Publications
PHD PROGRAM
Toxicology
RESEARCH INTEREST
Physiology, Toxicology

Mechanistic toxicology, hepato-toxicology, research translation, biomarkers


Willett, Christopher
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Publications
PHD PROGRAM
Biology

My lab concentrates on studying the molecular genetic basis of the evolutionary processes of adaptation and speciation. The questions we ask are what are the sequence changes that lead to variation between species and diversity within species, and what can these changes tell us about the processes that lead to their evolution. We use a number of different techniques to answer these questions, including molecular biology, sequence analyses (i.e. population genetics and molecular evolution techniques), physiological studies, and examinations of whole-organism fitness. Currently work in the lab has focused on a intertidal copepod species that is an excellent model for the initial stages of speciation (and also provides opportunities to study how populations of this species adapt to their physical environment).


Early life and adult pain can have drastic effects on neurodevelopment and overall quality of life. In the Williams’ Pain, Aging, and Interdisciplinary Neurobehavioral (P.A.I.N.) Lab, our research focuses on behavioral neuroscience and the mechanisms of neurobiology and neurophysiology of pain processing, with a special emphasis on the neonatal. The ultimate research goal is to better understand, recognize, and alleviate pain in the newborn to improve the quality of life in adulthood by uncovering new assessment tools and interventional strategies. Our research interests include the mechanisms of neurobiology and neurophysiology of pain processing, neonatal pain, chronic pain, neurobehavior, osteoarthritis, translational medicine, anesthesia/analgesics, and evoked and non-evoked pain assessment tools. The P.A.I.N. Lab has both pre-clinical and clinical studies to help close the gap in translation.


Our research is focused on two general areas:  1. Autism and 2. Pain.  Our autism research is focused on topoisomerases and other transcriptional regulators that were recently linked to autism.  We use genome-wide approaches to better understand how these transcriptional regulators affect gene expression in developing and adult neurons (such as RNA-seq, ChIP-seq, Crispr/Cas9 for knocking out genes).  We also assess how synaptic function is affected, using calcium imaging and electrophysiology.   In addition, we are performing a large RNA-seq screen to identify chemicals and drugs that increase risk for autism.   /  / Our pain research is focused on lipid kinases that regulate pain signaling and sensitization.  This includes work with cultured dorsal root ganglia (DRG) neurons, molecular biology and behavioral models of chronic pain.  We also are working on drug discovery projects, with an eye towards developing new therapeutics for chronic pain.