BBSP Faculty

Our lab develops new chemistry, and chemical agents as biological probes and drug discovery candidates. Current interests include the discovery of unconventional opioid agents, anti-tuberculosis drugs, and basic biochemistry of androgen biosynthesis inhibitors.

Dr. Benhabbour’s academic research focuses on development of novel tunable delivery platforms and polymer-based devices to treat or prevent a disease. Her work combines the elegance of organic and polymer chemistry with the versatility of engineering and formulation development to design and fabricate efficient and translatable nanocarriers and drug delivery systems for cancer treatment and HIV prevention.

Dr. Benhabbour has also Founded her startup company Anelleo, Inc. (AnelleO) in 2016 to develop the first 3D printed intravaginal ring as a platform technology for women’s health.

Current technologies in development in Dr. Benhabbour’s Lab include:
– 3D Printed intravaginal ring technology: A) Multipurpose prevention technology (MPT) for prevention of HIV/STIs and unplanned pregnancy.
– Polymer based ultra-long-acting injectable implant for HIV prevention and treatment.
– Combinatory chitosan/cellulose nanocrystals thermoresponsive hydrogel system: A) Sub-Q or intraosseous injectable for treatment of osteoporosis; B) Bio-ink for 3D bioprinting; C) Scaffold for stem cell delivery (e.g. iNSCs for treatment of post-surgical glioblastoma.
– Mucoadhesive thin film for treatment of vulvodynia.
– Targeted nanoparticles and hydrogel scaffolds for treatment of NSCLC.

Research in my lab examines the neurobiological mechanisms underlying alcoholism and addiction. At present studies are focused on the interaction between stress-related systems and sensitivity to alcohol, in order to better understand the mechanisms that underlie increased alcohol drinking during stressful episodes. We use an array of behavioral (e.g., operant self-administration, drug discrimination) and behavioral pharmacology techniques, including targeted brain regional drug injections, to functionally evaluate the role of specific molecular targets. In parallel to the behavioral studies, we use immunohistochemistry and Western blot techniques to examine alterations in the expression of various molecular targets following stress exposure. We are also applying these techniques to examine and integrate the study of depression that emerges following stress hormone exposure.

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.

Research in the Bowers lab focuses on investigation of structure activity relationships and mechanisms of action of natural product-derived small molecule therapeutics. We employ a variety of methods to build and modify compounds of interest, including manipulation of natural product biosynthesis, chemical synthesis, and semi-synthesis. One major area of research in the lab is the rationale engineering of biosynthetic pathways to make bacterial drug factories. Compounds targeting transcriptional regulation of cancer as well as multi-drug resistant venereal infections are currently under investigation in the lab.

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.

Our research group uses several biochemical and structural techniques (e.g. enzyme assays, X-ray crystallography, and cryo-EM) to understand how molecular machines drive the cell cycle. Dysregulation of these enzymes results in numerous cancer types.

A growing body of work in the biomedical sciences generates and analyzes omics data; our lab’s work contributes to these efforts by focusing on the integration of different omics data types to bring mechanistic insights to the multi-scale nature of cellular processes. The focus of our research is on developing systems genomics approaches to study the impact of genomic variation on genome function. We have used this focus to study genetic and molecular variation in both natural and engineered cellular systems and approach these topics through the lens of computational biology, machine learning and advanced omics data integration. More specifically, we create methods to reveal functional relationships across genomics, transcriptomics, ribosome profiling, proteomics, structural genomics, metabolomics and phenotype variability data. Our integrative omics methods improve understanding of how cells achieve regulation at multiple scales of complexity and link to genetic and molecular variants that influence these processes. Ultimately, the goal of our research is advancing the analysis of high-throughput omics technologies to empower patient care and clinical trial selections. To this end, we are developing integrative methods to improve mutation panels by selecting more informative genetic and molecular biomarkers that match disease relevance.

The overall goal of our lab is to perform research that contributes to a better understanding of pancreatic cancer biology and leads to improved treatments for this disease. One major focus of our studies is the metabolic activity, autophagy, which is a self-degradation process whereby cells can orderly clear defective organelles and recycle macromolecules as a nutrient source. Current projects are focused on further advancing autophagy inhibition as an anti-RAS therapeutic approach, as well as delineating other metabolic consequences of RAF-MEK-ERK MAPK inhibition.

Our lab is trying to understand the mechanisms by which long noncoding RNAs orchestrate the epigenetic control of gene expression. Relevant examples of this type of gene regulation occur in the case of X-chromosome inactivation and autosomal imprinting. We specialize in genomics, but rely a combination of techniques —  including genetics, proteomics, and molecular, cell and computational biology — to study these processes in both mouse and human stem and somatic cell systems.

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.

The overriding goal of Dr. Coleman’s work is to identify novel treatments for alcohol use disorders (AUD) and associated peripheral disease pathologies. Currently, this includes: the role of neuroimmune Signaling in AUD pathology, the role of alcohol-associated immune dysfunction in associated disease states, and novel molecular and subcellular mediators of immune dysfunction such as extracellular vesicles, and regenerative medicine approaches such as microglial repopulation.

The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment.  Students interested in a rotation in the DeSimone group should not contact Dr. DeSimone directly.  Instead please contact Chris Luft at jluft@email.unc.edu.

Sleep is an essential and evolutionarily conserved process that modifies synapses in the brain to support cognitive functions such as learning and memory. We are interested in understanding the molecular mechanisms of synaptic plasticity with a particular interest in sleep. Using mouse models of human disease as well as primary cultured neurons, we are applying this work to understanding and treating neurodevelopmental disorders including autism and intellectual disability. The lab focuses on biochemistry, pharmacology, animal behavior and genetics.

We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.

The Dominguez lab studies how gene expression is controlled by proteins that bind RNA. RNA binding proteins control the way RNAs are transcribed, spliced, polyadenylated, exported, degraded, and translated. Areas of research include: (1) Altered RNA-protein interactions in cancer; (2) RNA binding by noncanonical domains; and (3) Cell signaling and RNA processing.

The Drewry lab is focused on designing, synthesizing, evaluating, and sharing small molecule chemical probes for protein kinases. These tools are used to build a deeper understanding of disease pathways and facilitate identification of important targets for drug discovery. Through wide ranging partnerships with academic and industrial groups, the Drewry lab is building a Kinase Chemogenomic Set (KCGS) that is available to the community for screening.

The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks

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 lab studies the underlying structural and functional substrates of behavior in disease using rodent models. Specifically our goal is to develop a better understanding of how cellular function in the CNS is affected by drug-related substances (opioids, cannabinoids) in the context of HIV infection. That includes the study of how drugs of abuse exacerbate the pathogenesis of neuroAIDS but also the study of targets within the endocannabinoid system for the potential treatment of HIV. We use various in vivo and in vitro techniques, including primary cell culture models, behavioral conditioning tasks, live cell imaging, and electrophysiology.

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.

The Neurotoxicology Group examines the role of microglia interactions with neurons and the associated immune-mediated responses in brain development and aging as they relate to the initiation of brain damage, the progression of cell death, and subsequent repair/regenerative capabilities.  We have an interest in the neuroimmune response with regards to neurodegenerative diseases such as, Alzheimer’s disease.

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.

Our preclinical research is based on the concept that drugs of abuse gain control over behavior by hijacking molecular mechanisms of neuroplasticity within brain reward circuits. Our lab focuses on three main research questions: (1) Discover the neural circuits and molecular mechanisms that mediate the reinforcing and pleasurable subjective effects of alcohol and other drugs, (2) Identify the long-term effects of cocaine and alcohol abuse during adolescence, (3) Identify novel neural targets and validate pharmacological compounds that may be used to treat problems associated with alcohol and drug abuse. The lab culture is collaborative and dynamic, innovative, and team-based. We are looking for colleagues who share an interest in understanding how alcohol hijacks reward pathways to produce addiction.

Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention.

Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.

The Jones lab is interested in heterotrimeric G protein-coupled signaling and uses genetic model systems to dissect signaling networks.  The G-protein complex serves as the nexus between cell surface receptors and various downstream enzymes that ultimately alter cell behavior. Metazoans have a hopelessly complex repertoire of G-protein complexes and cell surface receptors so we turned to the reference plant, Arabidopsis thaliana, and the yeast, Saccharomyces cerevisiae, as our models because these two organisms have only two potential G protein complexes and few cell surface receptors.  Their simplicity and the ability to genetically manipulate genes in these organisms make them powerful tools.  We use a variety of cell biology approaches, sophisticated imaging techniques, 3-D protein structure analyses, forward and reverse genetic approaches, and biochemistries.

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.

Craig Lee, Pharm.D, Ph.D. is a professor in the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experimental Therapeutics (DPET). A key aspect of DPET’s mission is to optimize drug therapy through translating experimental and clinical pharmacology discoveries into precision medicine and accelerating application of these discoveries to improve patient care.

Dr. Lee is trained as a clinical/translational pharmaceutical scientist with expertise in cytochrome P450 metabolism, cardiovascular experimental therapeutics, and precision medicine/pharmacogenomics. He is an active member of the UNC McAllister Heart Institute and UNC Program for Precision Medicine in Healthcare, and has an adjunct faculty appointment in the UNC School of Medicine’s Division of Cardiology.

The overall objective of Dr. Lee’s research program is to improve the understanding of the central mechanisms underlying inter-individual variability in drug response as a means to develop novel therapeutic strategies that will improve public health. A major scientific focus of the Lee laboratory is the metabolism of drugs and eicosanoids by the cytochromes P450 enzyme system. The major therapeutic area of application of their research is cardiovascular and metabolic disease.

The Lee laboratory seeks to identify and elucidate the key factors that exacerbate inter-individual variability in the metabolism of and response to drugs currently on the market, and determine whether implementation of genomic and biomarker-guided drug selection and dosing strategies can reduce this variability in metabolism and response and improve patient outcomes. The Lee laboratory also seeks to develop a thorough understanding of how cytochrome P450-derived eicosanoids (bioactive lipid mediators of arachidonic acid) regulate hepatic and extra-hepatic inflammatory responses, and determine whether modulation of this pathway will serve as an effective anti-inflammatory and end-organ protective therapeutic strategy for cardiovascular and metabolic disease. Using genomics and biomarkers, the lab seeks to translate their preclinical discoveries into humans and determine which subsets of the population may be most likely to respond to the therapeutic strategies under evaluation in the laboratory.

The Lee laboratory is a highly collaborative and translational research program that integrates mechanistically-driven rodent and cell-based preclinical models with observational and interventional clinical studies. They have received funding from the National Institutes of Health and American Heart Association, authored over 100 manuscripts and over 100 abstracts in the areas of cytochromes P450, eicosanoid and drug metabolism, pharmacogenomics, and experimental therapeutics. Dr. Lee has served as the major research advisor for over 40 graduate students, post-doctoral fellows, and professional students.

I am a mathematical biologist interested in the biochemical and biophysical aspects of blood clotting and emergent behavior in biological fluid-structure interaction problems. I especially love mathematical modeling, where creativity, biological knowledge, and mathematical insight meet. My goal is to use mathematical and computational modeling as a tool to learn something new about a biological system, not just to simply match model output to experimental data. My research paradigm includes an integration of mathematical and experimental approaches, together with statistical analyses and inference, to determine mechanisms underlying complex biological phenomena. This paradigm culminates in the contextualization of my findings to both the mathematical and biological communities. My research program is focused mainly on studying the influence of biochemical and biophysical mechanisms on blood coagulation, clot formation, and bleeding.

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.

Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis and the development of therapeutic strategies for the treatment of neuroinflammation. Inflammatory changes within the brain caused by the viral infection initiate a toxic cascade that disrupts normal neural function and can eventually lead to neuronal death. To explore the mechanisms responsible for this damage, we investigate changes in calcium homeostasis, glutamate receptor function and inflammatory responses in primary neuronal, microglial and macrophage cultures. New therapeutic approaches targeted to signal transduction pathways and calcium regulation that protect the neurons and reduce inflammation are under investigation.

Our laboratory is focused on translating novel molecular biomarkers into clinical oncology practice, with the overarching goal of improving the care and survival of patients with cancer. Our group is highly collaborative and applies genomic, genetic, bioinformatic, informatic, statistical, and molecular approaches. Current projects in the laboratory include:

1. Correlative genomic testing to support clinical trials
2. Expanded clinical applications of RNA sequencing
3. Development and application of cell-free circulating tumor nucleic acid assays

Our research is focused on the development of novel theoretical and computational methods and AI techniques, which greatly enhance computer simulations and facilitate simulation analysis, and the application of these methods, making unprecedented contributions to biomolecular modeling and drug discovery. In collaboration with leading experimental groups, we combine complementary simulations and experiments to uncover functional mechanisms and design drugs of important biomolecules, including G-protein-coupled receptors (GPCRs), membrane-embedded proteases, RNA-binding proteins, and RNA. At the interface of computational biology, chemistry, biophysics, bioinformatics and pharmacology, our research aims to address three major topics: (i) development of biomolecular enhanced sampling and AI techniques, (ii) multiscale computational modeling of critical cellular signaling pathways, and (iii) AI-driven drug discovery of medically important proteins and RNA for treatments of neurological disorders, heart failure and cancers.

My laboratory has two main interests: 1) Regulation of P2Y receptor signaling and trafficking in epithelial cells and platelets. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of polarized epithelial cells and the regulation of P2Y receptor signaling during ADP-promoted platelet aggregation. 2) Antibiotic resistance mechanisms. We investigate the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporins. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.

The Palmer lab investigates combination cancer therapy: understanding the mechanisms of successful drug combinations to inform the development of combinations with new cancer therapies. Our approach is a synthesis of experiments, analysis of clinical data, and modeling. Students can pursue projects that are experimental, computational, or a mixture of both. Our goals are to improve the design of drug combinations, the interpretation of clinical trials, and patient stratification to increase rates of response and cure through more precise use of cancer medicines in combinations.

We are interested in unraveling the molecular basis for human disease and discover new treatments focused on human and microbial targets. Our work extends from atomic-level studies using structural biology, through chemical biology efforts to identify new drugs, and into cellular, animal and clinical investigations. While we are currently focused on the gut microbiome, past work has examined how drugs are detected and degraded in humans, proteins designed to protect soldiers from chemical weapons, how antibiotic resistance spreads, and novel approaches to treat bacterial infections. The Redinbo Laboratory actively works to increase equity and inclusion in our lab, in science, and in the world. Our lab is centered around collaboration, open communication, and trust. We welcome and support anyone regardless of race, disability, gender identification, sexual orientation, age, financial background, or religion. We aim to: 1) Provide an inclusive, equitable, and encouraging work environment 2) Actively broaden representation in STEM to correct historical opportunity imbalances 3) Respect and support each individual’s needs, decisions, and career goals 4) Celebrate our differences and use them to discover new ways of thinking and to better our science and our community

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.

Dr. Rizvi’s expertise is in imaging and therapeutic applications of light, bioengineered 3D models and animal models for cancer, and targeted drug delivery for inhibition of molecular survival pathways in tumors. His K99/R00 (NCI) develops photodynamic therapy (PDT)-based combinations against molecular pathways that are altered by fluid stress in ovarian cancer. He has co-authored 46 peer-reviewed publications and 5 book chapters with a focus on PDT, biomedical optics, and molecular targeting in cancer.

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.

Psychiatric disorders such as Anxiety and Autism Spectrum Disorders are often characterized by a rapid and amplified arousal response to stimuli (hyperarousal), which is often followed by a motivational drive to avoid such stimuli. Our lab studies the neuronal circuits that drive hyperarousal states by monitoring neuronal activity with single-cell precision using in vivo calcium imaging techniques in both head-fixed (two-photon microscopy) and freely-moving (miniature head-mounted microscopes) mice to record and track the activity of hundreds of individual neurons with both genetic and projection specificity.

The ultimate goal of our studies is to discover novel ways to treat human disease using G-protein coupled receptors.

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 Singleton Laboratory is interested in understanding the molecular basis for the develoment and transmission of microbial drug resistance and the discovery and exploitation of new strategies for controlling drug-resistant microorganisms. We develop and adapt synthetic chemistry and synthetic biology methods to provide new molecular tools — both biologically active small molecules and innovative platforms — for hypothesis-driven biological research and pharmaceutical discovery. These foundations of our program offers both chemically-oriented and biologically-oriented researchers new opportunities for the development of integrated, multi-disciplinary knowledge and technologies.

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.

I study complex traits using linkage, association, and genetic epidemiological approaches.  Disorders include schizophrenia (etiology and pharmacogenetics), smoking behavior, and chronic fatigue.

The Tarantino lab studies addiction and anxiety-related behaviors in mouse models using forward genetic approaches. We are currently studying a chemically-induced mutation in a splice donor site that results in increased novelty- and cocaine-induced locomotor activity and prolonged stress response. We are using RNA-seq to identify splice variants in the brain that differ between mutant and wildtype animals. We are also using measures of initial sensitivity to cocaine in dozens of inbred mouse strains to understand the genetics, biology and pharmacokinetics of acute cocaine response and how initial sensitivity might be related to addiction. Finally, we have just started a project aimed at studying the effects of perinatal exposure to dietary deficiencies on anxiety, depression and stress behaviors in adult offspring. This study utilizes RNA-seq and a unique breeding design to identify parent of origin effects on behavior and gene expression in response to perinatal diet.

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?

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.

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 translational research lab is focused on the earliest changes that occur in the uterus (endometrium) during cancer development related to obesity and hereditary DNA repair defects. We use preclinical tools (rodents, organoids, and cell lines) to probe mechanisms of endometrial cancer pathogenesis, in parallel with human tissue studies. Our overall goal is to understand how environmental factors, including obesity, hormones, and other exposures, influence endometrial cancer development and disparities so that we can use pharmacologic agents to prevent or reverse cancer development.

We are a translational cancer research lab. The overall goal of our research is to find therapeutic targets and biomarkers for patients with pancreatic cancer and to translate our results to the clinic. In order to accomplish this, we analyze patient tumors using a combination of genomics and proteomics to study the patient tumor and tumor microenvironment, identify and validate targets using forward and reverse genetic approaches in both patient-derived cell lines and mouse models. At the same time, we evaluate novel therapeutics for promising targets in mouse models in order to better predict clinical response in humans.

Our lab studies lipid signaling pathways that are involved in development and diseases by developing novel chemical probes and technologies. As key components of cellular membranes, lipids also serve as signaling molecules and modify functions of proteins through either covalent or non-covalent interactions. Dys-regulation of lipid signaling has been correlated with various diseases including cancer, diabetes, and neurodegenerative diseases. Consequently, many lipid-related proteins or processes have been used as therapeutic targets. However, lipids are dynamically metabolized and transported, making it difficult to illustrate the roles of lipids in development and diseases with limited availability of probes and technologies for lipid studies. The active projects in the lab include: 1) develop novel technologies to synthesize complex lipids, particularly phosphatidylinositides, and identify their interacting proteins in live cells; 2) develop new small molecule sensors and inhibitors for lipid metabolic enzymes such as PI3K and PLC; and 3) investigate cellular functions of lipids on different processes, particularly those regulated by small GTPases.