Development Core

Dr. Amanda Brown, Co-Director

Dr. Ahmet Hoke, Director

Core Mission

The core mission of the development core is to identify and support research projects that address the most urgent problems in the area of HIV-associated neurocognitive disorders

Goals and Objectives

• Promote innovative hypothesis driven, high-risk, high-impact neuroAIDS research with aims relevant to the mission of NIMH
• Promote new kinds of cross-disciplinary collaborations
• Encourage the participation of new and established investigators
• Generate data and publications for use in applying for NIH and other peer funding

The Development Core has been largely successful in accomplishing these goals:

• Number of Pilot Grants Awarded: 33
• Total Pilot Dollars Awarded (2007-14): $800,000
• Number of manuscripts published: 126
• Number of subsequent grant applications: 37
• Number of subsequent grants awarded: 21
• Funding sources of subsequent grants: NIH, Gilead Foundation, Maryland Stem Cell, Howard Hughes Medical Institute
• Dollar Amount of subsequent grants (FY15): $6,916,490
• Return on investment (ROI): 7.64 or 764%

Several of the funded pilot projects have been collaborations between investigators with expertise in distinct areas of neuroscience and in a few cases, interdisciplinary in nature. In one collaboration, pilot data generated helped to further the aims of the Therapeutic Core and led to preliminary data for other program project grants.

The pilot program supported studies in a variety of areas in the NeuroAIDS field including molecular and cellular neuroscience, clinical, neuroimaging and animal studies thereby taking advantage of the expertise of the faculty at Johns Hopkins. One pilot project is focused on examining the relationship between aging and HIV-associated neurocognitive disorder using neuroimaging, while another aims to understand the activation of brain endothelium in HAND, both timely and emerging areas of investigation in neuroAIDS.

Through the suggestions and assistance of members of the JHU NIMH Center, pilot awardees used the valuable resources of the MACS and SHCS cohorts. The pilot grants allowed the pursuit of novel directions with a focus on the most at-risk populations under guided academic mentoring that might not otherwise have been accomplished due to lack of funds. We expect that the full impact of the Development Core on the research capacity of JHU will be realized as more recently funded projects come to fruition and mature projects continue to grow.

Pilot Awardees 2018-2019

1. Carlo Colantuoni, PhD
   Title: "iPSC-Derived Neural Systems to Explore HIV-Associated Cognitive Impairment (HIV-CI)"
2. Leah Rubin, PhD, MPH
   Title: "Soluble and cellular immune activation and inflammation markers in detrimental cognitive change despite suppression of plasma RNA in HIV-infected women"
3. Michael Nedelcovych, PhD
   Title: "Glutamine Antagonism as a Novel Therapeutic Approach for HIV-Associated Neurocognitive Disorders (HAND)"
4. Seung Wan Yoo, PhD
   Title: "Inhibition of HIV replication with novel small molecule inhibitors of neutral sphingomyelinase 2"
5. Tory Johnson, PhD
   Title: "Detecting Tat from human serum samples"

Pilot Awardees 2015-2016

1. Charlene Gamaldo, M.D., FAASM, FAAN
   Title: “The Application of Mobile Health Technology as an Effective Tool to Improve the Sleep Health Care of Seropositive HIV Individuals”
2. Takashi Tsukamoto, Ph.D.
   Title: “Preclinical evaluation of the therapeutic utility of system x_c^-  inhibition in HAND”
3. Charles Bailey, DVM Dipl. ACVP
   Title: “TREM2 in the Macaque Model of HAND: Determining the Role of TREM2 in HIV-associated Neurocognitive Disorders”
4. Camilo Rojas, Ph.D.
   Title: ” Identification of Inhibitors of Serine Palmitoyl Transferase to Use as Chemical Probes in Models of HAND”

Pilot Awardees 2014-2015

1. Kelly Pate, D.V.M., Ph.D.
   Research Study Title: "A mouse model of the role of platelets in the establishment of latent viral reservoirs"
2. Rana Rais, Ph.D.
   Research Study Title: "Evaluation of system x_c^- inhibition in preclinical models of neuroAIDS"
3. Camilo Rojas, P.hD.
   Research Study Title: "Inhibition of neutral sphingomylinase 2 for the treatment of HAND"
4. David Graham, Ph.D.
   Research Study Title: "The study of simian immunodeficiency virus (SIV) pathogenesis in pigtailed and rhesus monkeys"

Pilot Awardees 2013-2014

1. Cherie Marvel, Ph.D.
   Research Study Title: "Examining the role of attentional bias on risk taking behavior in HIV-positive patients"

Pilot Awardees 2012-2013

1. Shilpa Buch, Ph.D.
   Research Study Title: "Role of endoplasmis reticulum stress in HIV Tat and cocaine-mediated cooperative activation of astrocytes: implications for HAND"
2. Ekaterina Dadachova, Ph.D.
   Research Study Title: "Elimination of HIV in CNS with armed antibodies to gp41 glycoprotein"
3. Kenneth Witwer, Ph.D.
   Research Study Title: "Development of miRNA-based therapies to silence or purge the latent macrophase reservoir in HAND"

Pilot Awardees 2007-2011: 21 additional pilot grants were awarded during those years that significantly contributed to the continued research success of its grantees and the JHU NIMH Center.

Recent Publication of interest:

Reward, Attention, and HIV-related Risk in HIV+ Individuals; October 17, 2015, Neurobiology of Disease
Brian A. Anderson, Sharif I. Kronemer, Jessica J. Rilee, Ned Sacktor, Cherie L. Marvel

ABSTRACT: Human immunodeficiency virus (HIV) is often contracted through engaging in risky reward-motivated behaviors such as needle sharing and unprotected sex. Understanding the factors that make an individual more vulnerable to succumbing to the temptation to engage in these risky behaviors is important to limiting the spread of HIV. One potential source of this vulnerability concerns the degree to which an individual is able to resist paying attention to irrelevant reward information. In the present study, we examine this possible link by characterizing individual differences in value-basedattentional bias in a sample of HIV + individuals with varying histories of risk-taking behavior. Participants learned associations between experimental stimuli and monetary reward outcome. The degree of attentional bias for these reward-associated stimuli, reflected in their ability to capture attention when presented as task-irrelevant distractors, was then assessed both immediately and six months following reward learning. Value-driven attentional capture was related to substance abuse history and non-planningimpulsiveness during the time leading up to contraction of HIV as measured via self-report. These findings suggest a link between the ability to ignore reward-associated information and prior HIV-related risk-taking behavior. Additionally, particular aspects of HIV-associated neurocognitive disorders were related to attentional bias, including motor deficits commonly associated with HIV-induced damage to the basal ganglia.

Read full article: Reward, attention, and HIV-related risk in HIV+ individuals
 

Core Members

Ahmet Hoke, M.D., Ph.D. (Director)
Amanda Brown, Ph.D. (Co-Director)
 

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