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

HIV Tat & Cocaine-Mediated Induction of Astrogliosis: Â Role of ER Stress in HAND
PI: S. Buch
Source: NIH/NIDA 1 R01 DA036157-01
This project aims to explore the role of co-operative effects of HIV protein Tat and cocaine on activation of astrocytes with the role of endoplasmic stress pathways in this process.

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
PI: H. Fox; Core Leader: S. Buch
Source: NIH/NIMH 3P01MH062261
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.

HIV Tat and Morphine Induce Microglial Migration and Activation via Release of miR-9 and 138
MPI: S. Buch/H. Fox
Source: NIH/NIDA 5R01DA040397
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.

NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
PI: H. Gendelman; Co-I, Project 2, S. Buch
Source:  NIH/NIDA 5P01DA028555
This is an integrative cross approach translational and multi-investigator program grant seeking to develop nanoformulated antiretroviral drug therapy from the bench to the patient.

PDGF-BB Reverses Impaired Neurogenesis Mediated by Tat and Cocaine
PI: S. Buch
Source:NIH/NIDA 1 R01 DA033150-05
Cocaine, a highly potent and addictive brain stimulant, often abused by HIV-infected patients, is known to exacerbate HIV-associated CNS disease while reducing the proliferative and differentiation capacity of the stem cell pool. This proposal is aimed at understanding molecular mechanisms by which a novel target PDGF- B chain, reverses the combined deleterious effects of HIV-1 protein Tat and cocaine on neural progenitor stem cells both in cell culture and in the whole animals.

HIV gp120 and chronic obstructive pulmonary disease
PI: Sopori; Co-I: Buch
Source:  JK150954
The goal of this application is to understand the role of viral envelope protein gp120 in regulating HIV-associated chronic pulmonary obstructive disease.

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

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


Techniques used in the laboratory

Personnel

Shannon Callen
Research Coordinator
402-559-3121
Shannon Callen
Ernest Chivero, Ph.D.
Instructor
Ernest Chivero

Blake Dallon
Research Technologist I

Blake Dallon
Minglei Guo, Ph.D.
Assistant Professor
 Minglei Guo
Dan Feng
Research Technologist I
Dan Feng
Guoku Hu, Ph.D.
Assistant Professor
Guoku Hu
Yeon Hee Kook
Research Technologist I
Yeon Hee Kook

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
Fang Niu
Research Technologist I
Fang Niu

Palsamy Periyasamy, Ph.D.
Instructor

Palsamy Periyasamy

Susmita Sil, Ph.D.
Post Doc Research Associate

Susmita Sil

Annadurai Thangaraj
Post Doc Research Associate

Annadurai Thangaraj

Ashutosh Tripathi
Post Doc Research Associate

Ashutosh Tripathi

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