Dr. Buch's laboratory

Research Goals
Collaborators
Funding
Techniques used in the laboratory
Personnel
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Dr. Buch's Biographical information
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.


Collaborators:

Paul Cheny, Ph.D., University of Kansas Medical Center
Howard S. Fox, M.D., Ph.D., University of Nebraska Medical Center
Huangui Xiong, M.D., Ph.D., University of Nebraska Medical Center
Howard E. Gendelman, M.D., University of Nebraska Medical Center


Funding

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.

Opiate induced SIV-Neuropathogenesis: Role of miRNA-29b in the Periphery-CNS Crosstalk
PI: S. Buch
Source: NIH/NIDA 4R01DA35203
In the proposed project, we will use an established opiate dependent simian model of neuroAIDs combined with microRNA profiling to understand how periphery-CNS cross talk leads to disease progression. These findings could have ramifications for future development of miR-29b as a biomarker for HIV-associated neuronal toxicity in opiate abusers.

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.

Exosome-mediated anti-microRNA delivery in the CNS:  A Novel Therapeutic for HAND in opiate users
PI: G. Hu; Co-I: S. Buch
Source: NIH 1 R21 DA042704-01A1
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.

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.


Techniques used in the laboratory

Personnel

Maria Burkovetskaya
Research Technologist

Maria Burkovetskaya


Shannon Callen
Research Coordinator
402-559-3121

Shannon Callen
Ernest Chivero, Ph.D.
Instructor

Ernest Chivero

Raj Dave, Ph.D.
Instructor

Rajnish Dave, Ph.D.

Natasha Ferguson
Research Technologist I

Natasha Ferguson
Minglei Guo, Ph.D.
Assistant Professor
Minglei Guo

Guoku Hu, Ph.D.
Assistant Professor

Guoku Hu

Sushila Kumari
Student Scholar

Sushila Kumari

Ke Liao
Graduate Student

First Prize-Poster Presentation
27th Annual Inter-campus Virology Retreat
"The role of autophagy in HIV tat mediated disruption of BBB"

Kei Liao
Qiaoling Liu
Research Technologist I

Qiaoling LIu
Fang Niu
Research Technologist I

Fang Niu

Palsamy Periyasamy, Ph.D.
Instructor

Palsamy Periyasamy, Ph.D.


Prakash Pillai, Ph.D.
Visiting Assistant Professor

Prakash Pillai


Jason Selvaraj

Jason Selvaraj

Susmita Sil, Ph.D.
Instructor

Susmita Sil, PhD


Seema Singh, Ph.D.
Postdoc Research Associate

Seema Singh

Annadurai Thangaraj, Ph.D.
Instructor

Annadurai Thangaraj


Ashutosh Tripathi, Ph.D.
Post Doc Research Associate

Ashutosh Tripathi

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