Research

Vision: To build an organization nationally recognized for excellence in research.

Creating an environment that is conducive to both basic and clinical research and integrating the departmental basic science program with its clinical applications are the focus of the leadership. Dr. Tao, Vice Chair for Basic Research, is spearheading the efforts of our investigators. The following pages highlight the exciting breakthroughs our investigators have produced. Our work in both basic and clinical research, which will position us a leader in the field of perioperative medicine. 

Dr. Eloy, Vice Chair for Academic Affairs, leads our clinical research program. The Department conducts several industry-sponsored and investigator-initiated clinical trials.

Translational Research on Chronic Pain and Opioid-Associated Disorders in Dr. Tao’s Lab

Neuronal Mechanisms Research in Dr. Ye's Lab

Research in my lab aims to understand the specific neuronal mechanisms that underlie changes that contribute to the development of dependence on alcohol and other abuse substances (nicotine, cocaine, opiates, cannabis, etc.). We seek to understand the neural basis of substance use disorders and to identify the cellular and molecular mechanisms underlying drug use disorders and the comorbid anxiety, hyperalgesia, and depressive-like behaviors that contribute to relapse. We use combinatorial cutting-edge techniques including chemogenetic, optogenetic, ex vivo electrophysiology, molecular genetics, imaging, tract-tracing, immunohistochemistry, PCR and Western blots, stereotaxic surgery, intracranial microinjection, microdialysis techniques.  We use a variety of behavioral paradigms, including operant drug self-administration, tests of sensitivity to thermal and mechanical stimuli, tests of anxiety-like behaviors, tests of depressive-like behaviors, tests of learning, and memory. We use a variety of animal models of drugs use disorders, including alcohol vapor inhalation chambers, two-bottle free choice voluntary drinking, operant self-administration, etc. We hope that these studies will shed new light on the neural basis of some essential addictive behaviors and provide therapeutic implications for the treatment of drug use disorders.

Chronic Pain Research in Dr. Hu's Lab

Intracellular calcium is essential for cellular functions and the induction of synaptic plasticity, which contributes to the generation and the maintenance of pain hypersensitivity. Calcium levels are regulated by calcium influx through calcium permeable channels on the cell membrane. Store-operated calcium (SOC) channels are highly calcium-selective cation channels, composed of three pore-forming subunits Orai1/2/3 and activated by two Calcium sensors STIM1 and STIM2 (mainly located on the surface of the ER membrane). The SOC signaling is a major mechanism for calcium influx in non-excitable cells.  SOC channels are expressed in the CNS, however, the functional significance of SOC entry in the CNS remains unclear. It has been indicated that calcium influx through SOC channels play a critical role in synaptic transmission.  We have demonstrated that SOC channels are expressed in the spinal cord dorsal horn and dorsal root ganglion, the two main regions of the pain neuraxis.  Our in vivo studies reveal that inhibition of SOCs or deficiency of Orai1 attenuates pain hypersensitivity-induced by inflammation or nerve injury, suggesting an important role of SOC channels in chronic pain. The long term goal of my research is to understand the mechanisms underlying the development of chronic pain and to identify novel drug targets and drug candidates for the treatment of chronic pain. My research has been concentrated on the role of store-operated calcium channels (SOCs) in pain plasticity. Currently, we are identifying endogenous upstream molecules of the SOC signaling and exploring functional consequences of SOC channel activation. These studies will extend our knowledge of how SOC signaling modulates pain and will provide novel insights into mechanisms underlying chronic pain.  We hope to identify SOC channels as drug targets and develop new approaches to therapeutic intervention for chronic pain associated with nerve injury and diseases.

Parkinson's Research in Dr. Hilfiker's Lab

Dr. Sabine Hilfiker received her MS from the University of Basel, Switzerland in 1992 and her Ph.D. in Molecular Neuroscience from the Rockefeller University, New York in 1998, where she investigated molecular mechanisms of synaptic vesicle trafficking at the presynaptic nerve terminal under the supervision of Paul Greengard, Nobel Laureate 2000 in Medicine or Physiology. Following a short postdoctoral appointment at the Rockefeller University, Dr. Hilfiker was awarded a BBSRC David Phillips Research Fellowship to join the Faculty of Life Sciences at the University of Manchester, UK in 2000, where she continued her investigations into intracellular membrane trafficking events. Dr. Hilfiker obtained a Ramón y Cajal Fellowship at the CSIC in Spain in 2003, where she was appointed to tenured Principal Investigator in 2008. At the CSIC, she began her independent research program focused on Parkinson´s disease. She is recipient of the first Research Prize of the Spanish Federation for Parkinson´s Disease (2008), and member of the LRRK2 Biology Consortium of the Michael J. Fox Foundation since 2011. She joined the Department of Anesthesiology and the Center for Immunity and Inflammation as an Associate Professor in August 2019. The Hilfiker laboratory primarily investigates the molecular and cellular pathways leading to Parkinson´s disease, one of the major age-related, chronic and progressive neurodegenerative disorders.

Neurobiology of Neuropsychiatric Disorders and Drug Development in Dr. Xu's Lab

Neuropsychiatric disorders affecting memory, cognition, depression, and neuropathic pain, such as Alzheimer’s disease (AD), traumatic brain injury (TBI), and alcohol abuse, impact millions of Americans. Compelling evidence suggests that mitochondrial dysfunction is an early feature in susceptible neurons within the brain in these disorders, playing a critical role in their pathogenesis. However, the underlying molecular mechanisms remain unclear. Dr. Xu’s lab research is divided into three parts:

1. Phosphodiesterases (PDEs) are a family of enzymes that contribute to the hydrolysis of cAMP and cGMP, second messengers that control important cellular functions. Among PDE subtypes, PDE2A is broadly expressed in brain regions susceptible to neuropsychiatric diseases. Our project aims to decipher whether aberrant PDE2A signaling results in an imbalance in mitochondrial dynamics, adversely impacting neuronal and synaptic function, and leading to pathological deficits in these neuropsychiatric disorders.
2. Although dozens of compounds have been reported to reduce neuropsychiatric symptoms in preclinical studies, these drugs have not proven beneficial in ameliorating cognitive and emotional disorders in patients with neuropsychiatric disorders. Our project aims to accelerate the development of highly selective inhibitors targeting PDE2 and PDE4 isoforms as novel treatments for illnesses affecting memory, cognitive, and emotional functions, such as AD, TBI, and dementias induced by alcohol abuse.
3. Recent studies have been involved in exploring the relationship between the imbalance in mitochondrial dynamics and aging-related neuropathic pain.

Research on molecular and cellular mechanisms of opioid action In Dr. Pan’s Lab

Most clinically used opioid drugs including morphine and fentanyl, as well as drugs of abuse such as heroin, act through mu opioid receptors. The single-copy gene encoding mu opioid receptors, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple receptor isoforms or variants that are conserved from rodent to human. These OPRM1 isoforms or variants can be categorized into three structurally distinct types: 1) full-length seven transmembrane (TM) carboxyl (C)-terminal variants, 2) truncated 6TM variants excluding the first TM, and 3) truncated single TM variants that contain only the first TM. Dr. Pan’s laboratory studies the molecular and cellular mechanisms of opioid actions via OPRM1 splice variants using integrative state-of-the-art molecular, biochemical, pharmacological and behavioral approaches, as well as gene targeting mouse/rat models. These studies provide the foundation for developing novel opioid analgesics that have potent analgesic actions devoid of side effects. For example, Dr. Pan’s laboratory established the functional relevance of the truncated 6TM variants in mediating the actions of a novel class of opioid, such as 3-iodobenzoyl-6beta-naltrexamide (IBNtxA). IBNtxA is potent against thermal, inflammatory, and neuropathic pain in animal models and does not produce respiratory depression, physical dependence, or reward behavior. One derivative of IBNtxA, SBS1000, is currently in Phase I clinical trial. Dr. Pan’s laboratory has long supported by NIH grants with a track record of publications in peer-reviewed journals.

A detailed list of the department’s scholarly activity can be found below.

Scholarly Activities 2019 – 2020

Scholarly Activities 2018 – 2019

Basic Science Awards 2019-2020

Clinical Trials 2019-2020