The purpose of Dr. Jennifer Iudicello's K23 application is to provide focused training and mentoring in the neurobiological aspects of methamphetamine (METH) addiction and HIV disease that builds on her strong academic foundation in the neurocognitive and functional consequences of addictions and neuroAIDS in service of her long-term goals as an independent, transdisciplinary patient-oriented investigator. The proposed training, knowledge, and research experience will promote her development into an independent investigator capable of bridging laboratory neurobiological discoveries with their clinical expression and real-world impact among persons living with METH addiction and HIV disease. This work is of considerable

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because both of these conditions are prevalent, commonly co-occur, and exert adverse independent and combined effects on brain structure and function. The combined effects on brain structure and function is of critical clinical importance since neurocognitive impairment has been linked to poorer functional and health outcomes. Biomarkers of nervous system injury may be useful tools for understanding the neuropathological processes underlying METH- and HIV-associated neurocognitive and functional decline and could provide valuable insights for future drug development. This K23 application proposes to determine the associations between a unique panel of biomarkers in METH and HIV specifically chosen to reflect the structural and functional integrity of essential components of the blood-brain barrier (BBB) including endothelial cell adhesion molecules, tight junction proteins (TJPs), and basement membrane proteins and METH- and HIVassociated neurocognitive and functional decline. The focused training and research goals of this K23 fill a critical gap in Dr. Iudicellos past training by enabling her to: 1) Gain knowledge and expertise in METH- and HIV-associated neurobiology, with a particular emphasis on the BBB;2) Gain both practical hands-on (e.g., biomarker assay development) and analytic experience that will allow for proficiency in biomarker data collection, analysis, and interpretation;3) Apply the knowledge and skills acquired through applied and didactic training by conducting independent research on the associations between biomarkers of BBB injury and METH- and HIV-associated neurocognitive and functional declines, which will subsequently lead to new R21 and R01 applications;and 4) Disseminate research in order to advance the science and practice of addictions and neuroAIDS, promote research collaborations, and stimulate the development of of innovative research ideas and future directions. To facilitate the successful completion of her training objectives and career goals, Dr. Iudicello has assembled an accomplished, multidisciplinary team of mentors with expertise in all areas of research relevant to this project, including biomarkers and infectious diseases (Primary Mentor, Dr. Scott Letendre), neurovascular injury (Co-Mentor, Dr. Ronald J. Ellis), neuropsychology and functional outcomes (Co-Mentor, Dr. Robert K. Heaton), neuroscience and addictions (Co-Mentor, Dr. Igor Grant), advanced statistics (Co-Mentor, Dr. Florin Vaida), and biomarkers specific to BBB injury in METH and HIV (Consultant, Dr. Yuri Persidsky). When combined with well-established resources and strong infrastructure of the UCSD HIV Neurobehavioral Research Program (HNRP) and the Translational Methamphetamine AIDS Research Center (TMARC), this K23 award will provide critical support that will allow Dr. Iudicello to attain her short- and long-term goals of becoming an influential independent clinical researcher with transdisciplinary expertise that will help advance the field of addictions and neuroAIDS and improve the lives of individuals affected by these conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DA037793-01
Application #
8730973
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Purohit, Vishnudutt
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Woods, Steven Paul; Iudicello, Jennifer E; Morgan, Erin E et al. (2016) Health-Related Everyday Functioning in the Internet Age: HIV-Associated Neurocognitive Disorders Disrupt Online Pharmacy and Health Chart Navigation Skills. Arch Clin Neuropsychol 31:176-85
Kamat, Rujvi; Doyle, Katie L; Iudicello, Jennifer E et al. (2016) Neurobehavioral Disturbances During Acute and Early HIV Infection. Cogn Behav Neurol 29:1-10
Kamat, Rujvi; Woods, Steven Paul; Cameron, Marizela V et al. (2016) Apathy is associated with lower mental and physical quality of life in persons infected with HIV. Psychol Health Med 21:890-901
Morgan, Erin E; Iudicello, Jennifer E; Cattie, Jordan E et al. (2015) Neurocognitive impairment is associated with lower health literacy among persons living with HIV infection. AIDS Behav 19:166-77
Sheppard, David P; Iudicello, Jennifer E; Bondi, Mark W et al. (2015) Elevated rates of mild cognitive impairment in HIV disease. J Neurovirol 21:576-84
Gupta, Saurabh; Iudicello, Jennifer E; Shi, Chuan et al. (2014) Absence of neurocognitive impairment in a large Chinese sample of HCV-infected injection drug users receiving methadone treatment. Drug Alcohol Depend 137:29-35
Gongvatana, Assawin; Morgan, Erin E; Iudicello, Jennifer E et al. (2014) A history of alcohol dependence augments HIV-associated neurocognitive deficits in persons aged 60 and older. J Neurovirol 20:505-13
Marquine, Maria J; Iudicello, Jennifer E; Morgan, Erin E et al. (2014) ""Frontal systems"" behaviors in comorbid human immunodeficiency virus infection and methamphetamine dependency. Psychiatry Res 215:208-16
Fazeli, Pariya L; Doyle, Katie L; Scott, J Cobb et al. (2014) Shallow encoding and forgetting are associated with dependence in instrumental activities of daily living among older adults living with HIV infection. Arch Clin Neuropsychol 29:278-88
Iudicello, Jennifer E; Morgan, Erin E; Gongvatana, Assawin et al. (2014) Detrimental impact of remote methamphetamine dependence on neurocognitive and everyday functioning in older but not younger HIV+ adults: evidence for a legacy effect? J Neurovirol 20:85-98