Dr. Buch's laboratory

Research Goals
Techniques used in the laboratory
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Lab phone: 402-559-3166

Research Goals:

The long term goal of our group is to identify novel therapeutic strategies that may enhance neuronal function and survival in NeuroAIDS, with possible implications in other neurodegenerative diseases.


Paul Cheny, PhD, University of Kansas Medical Center
Howard S. Fox, MD, PhD, University of Nebraska Medical Center
Huangui Xiong, MD, PhD, University of Nebraska Medical Center
Howard E. Gendelman, MD, University of Nebraska Medical Center


PDGF-CC Mediated Reversal of Synaptodendritic Injury in HAND
PI: S. Buch
Source: NIH/NIMH 5R01MH106425
The overarching goal of this application is to explore the role of platelet-derived growth factor (PDGF)-CC in reversing synaptodendritic injury & the associated cognitive decline, both of which comprise the hallmark features of HIV-associated neurocognitive disorders (HAND).  Combinatorial in vitro, in vivo and ex vivo approaches are proposed to test the efficacy of PDGF-CC as a therapeutic agent.

Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center
MPI: S. Buch and H. Fox
Source: NIH/NIMH 3P01MH062261
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.

The combinatorial effects of Opiates and the emerging promoter-variant strains of HIV-1 subtype C on HIV neuropathogensis and latency
PI: S. Buch
Source: NIH 1 R01 DA041751-01
In this proposal we plan investigate the involvement of the combinatorial effects of Opiates and the emerging promoter-variant strains of HIV-1 subtype C on HIV neuropathogensis and latency and testing this hypothesis in a primate model.

HIV Tat & cocaine-mediated alterations in microglial migration & activation involve epigenetic regulation or miRNAs
PI: S. Buch
Source: NIH 1 R01 DA043138-01 
The goal of this proposal is to explore how cocaine and HIV Tat modulate increased microglial activation and migration respectively, via DNA methylation of microRNA 124 promoter, leading in turn, to increased TLR4 signaling and also via up regulation of miR-9 leading to enhanced microglial migration

HIV Tat and Morphine Induce Microglial Migration and Activation via Release of miR-9 and 138
PI: S. Buch
Source: 5 R01 DA040397-05
This grant aims to explore how viral protein such as Tat induces miRNA-9 in exosomes from the astrocytes leading to increased migration of microglia. We also propose to understand how morphine exposure of astrocytes can upregulate miRNA-138 in exosomes, which leads to increased microglial activation. Together HIV proteins and opiates co-operate to inflict increased glial migration and activation, thereby contributing to disease severity.

The brain as a SIV reservoir under suppressive cART potentiation by drugs of abuse
MPI: H. Fox/S. Buch
Source:  NIH 1 R01DA043164
Using the SIV/macaque system, we will determine whether the brain is a viral reservoir in the setting of effective treatment, and will measure the effect of two commonly used drugs of abuse, morphine and methamphetamine, on the brain reservoir. Mechanisms by which drug abuse affect the viral reservoir will be examined, thus leading to strategies to target this reservoir to effect a cure in those with and without substance abuse.

HIV-1 mediated synaptodendritic injury and microglial activation:  Role of extracellular vesicle miRNAs
PI: G. Hu; Co-I: S. Buch
Source:  NIH R01MH112848
The goal of this project is to assess the molecular pathways by which PDGF-CC reverses the synaptodendritic injury induced by HIV Tat.

Combinatorial effects of HIV, cART, & morphine on neuroinflammation: implications for HAND
PI: M. Guo; Co-I: S. Buch
Source: NIH 5 R01 DA044586-03
In this grant, we will test the hypothesis via two specific aims - SA1: Investigate the molecular mechanism(s) underlying TAT, morphine & ARVs (3 drug regimen) mediated activation of microglia in vitro; and SA2: To determine the mechanisms underlying Tat, morphine and cART-mediated neuroinflammation in vivo in a rodent model of HAND.

Mechanisms underlying dysregulated neuroimmune signaling and neuronal dysfunction in HIV (+) individuals with cART and cocaine
PI: M. Guo; Co-I: S. Buch
Source: NIH 1 R01 DA047156-01
This grant is to explore the critical roles of NLRP3 inflammasome on microglial activation and the involvement of non-long coding RNA malat1 in neuronal injuries in the context of cocaine, cART, and HIV-TAT.

Molecular mechanisms underlying HIV & cocaine-mediated microglial activation: targeting NLRP3 inflammasome
MPI: S. Buch and M. Guo
Source:  NIH 1 R01 DA050545
In this proposal, we will assess the molecular signaling pathways by which the comorbidity of HIV and cocaine abuse exerts combinatorial activation of microglia in the brain with a focus on the multiprotein complex – the NLRP3 inflammasome. We will also test the efficacy of the NLRP3 inflammasome inhibitor in abrogating HIV and cocaine-mediated microglial activation in rodent models of HIV & cocaine administration. Understanding the mechanisms responsible for microglial activation induced by HIV & cocaine will set the stage for future development of novel therapeutics aimed at dampening the neuro-inflammatory responses.

Exosome-mediated anti-microRNA delivery in the CNS: A Novel Therapeutic for HAND in opiate users
MPI: G. Hu and S. Buch
Source: NIH R21 DA042704
MicroRNAs play important roles in regulation of disease pathogenesis including HIV associated cognitive impairment. Our goal in this grant is to develop therapeutic interventions using extracellular vesicle (EV)-based RNA drug delivery in vivo for the treatment of cognitive impairment in HIV-infected opiate abusers.

Rural Drug Addiction Research Center
PI: S. Buch
Source: University of Nebraska - Lincoln

Ocular Biological senescence evaluation & science study (OBSESSS)
PI: S. Buch
CRDF Global

Techniques used in the laboratory


Shannon Callen
Research Coordinator

Shannon Callen

Natasha Ferguson
Research Technologist I

Natasha Ferguson

Guoku Hu, PhD
Associate Professor

Guoku Hu

Muthukumar Kannan


Palsamy Periyasamy, PhD
Assistant Professor

Palsamy Periyasamy, PhD

Susmita Sil, PhD
Assistant Professor

Susmita Sil, PhD

Seema Singh, PhD
Post-Doctoral Fellow

Seema Singh

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