Laboratory of Xiu-Ti Hu, MD, PhD

Our work

I am a faculty member of the Department of Microbial Pathogens and Immunity in Rush University Medical Center at Chicago, IL. I have been a neuroscientist for more than 30 years.  My research mainly focuses on determine the impact of drugs of abuse, HIV-associated neurocognitive disorders (HAND; a.k.a. neuroAIDS or neuroHIV) and Alzheimer’s disease (AD), on the brain regions that are key regulators of neurocognition, either with or without the influence of aging. To date, I have published 63 peer-reviewed scientific articles, and have 2 more manuscripts currently under reviewing, plus 10 invited book chapters.

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Impact of work

Our lab made the following discoveries:
My early study focused on the effects of antipsychotic drugs, Parkinson’s diseases, and drug abstinence-associated neuronal dysfunction in the mesocorticolimbic and nigrostriatal dopamine systems, primarily in the medial prefrontal cortex (mPFC), ventral/dorsal striatum (a.k.a. the nucleus accumbens and caudate-putamen, respectively), and midbrain.  Similar to the hippocampus, these brain regions are the key regulators of neurocognition and addiction.  I contributed to pioneer the field of research regarding cocaine-induced maladaptations in voltage-gated ion channels and related signaling in the brain of rodents.  I and my colleagues demonstrated that, for the first time in the field, repeated cocaine exposure in vivo induces functional adaptations in the voltage-gated Na+, K+, and Ca2+ channels, as well as related intracellular signaling in neurons assessed ex vivo.  Such pathophysiology was found in different types of neurons in the mPFC and striatum that are associated with, and involved in, regulation of drug-induced behavioral alterations, which may contribute to the underpinnings of cocaine addiction.

In the past decade my research expends to reveal the HIV neuropathogenesis (with or without the impact of drugs of abuse), and to define the cellular/molecular mechanism underlying neuroHIV, with or without drug abuse.  Both HIV and psychostimulants (cocaine and methamphetamine) induce functional and anatomical alterations in the PFC, striatum, and hippocampus, the most vulnerable structures that are also profoundly altered by AD.  Dysfunction of these brain regions is associated with, and contributes to, the decline of cognition in HAND patients, while cocaine exacerbates the progression of HAND.  Elucidating the underlying mechanism(s) of such neuropathogenesis may help the development of novel therapeutic strategies to treat HAND, drug addiction, and the two comorbid diseases.  Moreover, given that HIV+ drug abusers are aging under the combined anti-retroviral therapy (cART), my research also focuses on assessing the impact of aging, as well as the side effects of cART, on the functional activity of mPFC and striatal neurons.

Recently, I initiate a study to determine the mechanism that may underlie the neurotoxicity seen in the PFC of AD.  The current beta-Amyloid (Aβ) theory for AD study may be wrong; and all clinical drug trails based on it have failed.  In addition, HAND could also progress to HIV-associated dementia (HAD), while drugs of abuse could exacerbate the decline of neurocognition, especially during aging.  It is possible that neurotoxicity-induced dysregulation, injury and death of neurons contribute to the underlying mechanism of AD-related dementia and HAD.  Thus, defining such mechanism may not only help us to establish a novel theory for AD and HAND study, but will also contribute to the development of new therapeutic strategies for treating these neurodegenerative diseases.

The neurotoxicity is induced by dysregulation of the neuronal calcium homeostasis. Our research team is currently studying the neuronal calcium dysregulation, the final path to the neurotoxicity, in animal models of AD, HAND and cocaine (or methamphetamine) abuse.  Specifically, we are working on (1) elucidating mechanism(s) that underlies AD, HIV and drugs of abuse-induced dysregulation of cortical/striatal neuron excitability (e.g., by studying dysfunctional voltage-gated L-type Ca2+ channels and K+ channels), (2) assessing the interplay of cortical neurons and astrocytes in the mPFC and striatum of rat model of AD, neuroHIV, drug abuse, or a combination of which; and (3) reducing such neurotoxicity by intervening neuronal overactivation induced by Aβ, HIV/cART, and cocaine.

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Technology

Electrophysiology (patch-clamp recording of neurons and astrocytes in brain slices or cell cultures), drug self-administration (cocaine and methamphetamine), biochemistry and molecular biology approaches are integratively utilized in my lab in combination with rodent models of these chronic brain diseases. Collaboration between my lab and others is actively ongoing in and out of Rush University.

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Funding

My research is currently funded by the following NIH agencies:

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Our team

  • Lihua Chen, PhD, research scientist
  • Nasreen Choudhury, PhD, postdoctoral fellow
  • Vivian Nguyen, research lab tech 3
  • Leannie Olivares, BS, research lab tech 1

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Contact us

Xiu-Ti Hu, MD/PhD
Professor
Dept. of Microbial Pathogens & Immunity
Rush University Medical Center
1735 W. Harrison Street
Cohn Research Building, Rm. 610
Chicago, IL 60612
Phone#: (312) 563-4560
Email: xiu-ti_hu@rush.edu

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