OHSU

Psychoneuroimmunology Research Lab

Psychoneuroimmunology Research Lab

Jennifer M. Loftis, Ph.D., Principal Investigator

Marilyn S. Huckans, Ph.D., Principal Investigator

Psychoneuroimmunology is the study of interactions between the immune and central nervous systems, and particularly how these interactions contribute to psychiatric function and health. The Psychoneuroimmunology (PNI) Research Lab, led by Drs. Huckans and Loftis, is a “real time”, translational research program that integrates human, animal, and in vitro experiments to examine how neuroimmune factors contribute to the neuropsychiatric effects of medical, psychiatric, and substance use disorders.

Brain Diagram

The Psychoneuroimmunology (PNI) Research Lab is led by Dr. Jennifer M. Loftis and Dr. Marilyn S. Huckans. Our long-term goal is an improved understanding of how the immune and central nervous systems interact to impact neuropsychiatric function. At high pathophysiological levels, immune factors such as cytokines, chemokines, and adhesion molecules regulate immune responses to pathogens and injury.  However, immune factors are also required at low physiological levels for the regulation of synaptic plasticity, normal neuronal function, and therefore normal mood and cognition.  Many conditions such as addiction and hepatitis C are associated with alterations in immune factor expression. The PNI Research Lab is interested in how these immune alterations then contribute to functional impairments—problems with cognition, depression, anxiety, and impulsivity. Within the delicate balance of these immune factors, there also exists significant potential for intervention. The PNI Research Lab, therefore, strives toward discovery, development, and testing of novel treatments for psychiatric and substance use disorders.

About Us

The PNI Research LabPrincipal Investigators

Marilyn Huckans, Ph.D.
Jennifer M. Loftis, Ph.D.

Approach

The PNI Research Lab utilizes unique cross-species and translational methods designed to guide and inform one another and to ensure rapid progress from bench to bedside. We are funded through NIH and VA grants. Specific areas of interest include:

  • Investigating the relationships among cytokine-induced neuropsychiatric symptoms and associated changes in neurotransmitter systems, stress hormones, and neuronal plasticity and integrity.
  • Characterizing the effects of addiction on peripheral and central immune function, and developing and testing immunotherapies as a novel approach to addiction medicine. For example, the PNI Research Laboratory is currently evaluating the efficacy of peptide-based immunotherapies for the treatment of methamphetamine-induced cognitive impairments and neuroinflammation.    
  • The use of novel pharmacotherapies for the treatment or prevention of cytokine-induced psychiatric symptoms and sickness behavior (in animal models). 
  • Identifying genetic and neuroimmune biomarkers associated with cytokine-induced depression and cognitive impairment, such as the role of p38 mitogen-activated protein (MAP) kinase. Through the phosphorylation of other proteins, p38 MAP kinase can upregulate message transcription and increase protein expression of inflammatory mediators hypothesized to contribute to depressive symptoms.

Current Research

Pre-clinical testing of a novel immunotherapy [recombinant T cell receptor ligand (RTL)] to improve cognitive recovery and brain healing following methamphetamine dependence: From mice to men. This NIH challenge grant will characterize methamphetamine's effects on peripheral and central immune function, and it will pre-clinically test the therapeutic efficacy of RTL in reducing methamphetamine-induced cognitive impairment, neuronal loss, and neuroinflammation in mice.

Novel RTL treatment to promote brain repair and cognitive recovery following methamphetamine addiction. This NIH Phase 1 small business technology transfer (STTR) grant will determine if the ability of recombinant T cell receptor ligand (RTL)-551 to reverse methamphetamine-induced neuronal degeneration and cognitive dysfunction in mice is gender specific and must target myelin-specific T cells. These studies are crucial for evaluating the possible clinical application of a similar human RTL construct for treatment of subjects with methamphetamine addition.

Cognitive and cortical effects of hepatitis C and interferon therapy. The goal of this VA-funded study is to better characterize the effects of hepatitis C viral infection and interferon therapy on cognitive function, brain structure and function, and peripheral immune activation.

Inflammatory mediators in depression and HCV treatment. The goal of this VA-funded study is to investigate the influence of p38 MAP kinase inhibition on inflammatory gene regulation, cytokine expression and depressive-like behaviors in mice, and in humans with hepatitis C.

Faculty and Staff 

Principal Investigators:

Jennifer Loftis, Ph.D.

Associate Professor of Psychiatry, Oregon Health & Science University
Research Scientist, Portland VA Medical Center

Method of Contact:
Portland VA Medical Center, R&D 16
3710 SW US Veterans Hospital Road
Portland, Oregon 97239
loftisj@ohsu.edu
Phone:  503 220-8262 ext. 57155 (office) or ext. 54725 (lab)

Education:
BA, Psychology, University of California at Santa Barbara, 1990
BA, Economics, University of California at Santa Barbara, 1990
MA, Psychology, Fairleigh Dickinson University, 1994
PhD, Behavioral Neuroscience, Oregon Health & Science University (OHSU), 2002
Post-doctoral fellowship, Molecular Microbiology & Immunology, OHSU, 2004 - 2007

Research:
Dr. Jennifer Loftis is a Research Scientist at the Portland VA Medical Center and an Associate Professor in the Department of Psychiatry at OHSU. Her research is focused on investigating the neuroimmunological mechanisms contributing to depression and cognitive impairments, discovering treatment targets, and testing novel interventions for improving depression and neuropsychiatric recovery. Dr. Loftis’ translational research program uses rodent models (e.g., Flinders Sensitive Line rats) and humans to characterize inflammatory pathways involved in cognitive dysfunction and neuropsychiatric symptoms, particularly in patients with a history of substance abuse and hepatitis C viral infection.  Recently, she identified a novel role for cytokines in the development of depressive symptoms in patients with chronic hepatitis C, and this finding has led to the initial testing of hypotheses regarding how circulating inflammatory cytokines affect central nervous system functioning. Dr. Loftis’ long-term goal as a principal investigator is to expand our understanding of the biochemical and molecular mechanisms associated with neuropsychiatric impairments and CNS inflammation.

Teaching/Mentorship:
Dr. Loftis is an active mentor and teacher in the community.  At OHSU, she is a small group facilitator for the Principles of Clinical Medicine course within the School of Medicine, and a mentor for the Partnership for Scientific Inquiry. She also mentors for the STEM Mentor Project and is a member of the Neuroscientist/Teacher Partner Program to educate K-12 children in neuroscience and current research.

Administration/Service:
Dr. Loftis balances her research and teaching responsibilities with administrative and community service.  She serves as a member of the Portland VA Medical Center Institutional Animal Care and Use Committee (IACUC), the Portland VA Medical Center Research & Development Committee, and the OHSU Department of Psychiatry Promotions & Tenure Committee. 

Activities:
Research, Education and Administration/Service

Selected Recent Publications:
Loftis J.M., Choi D., Hoffman W.F., Huckans M. (in press). Methamphetamine causespersistent immune dysregulation:  A cross-species, translational report. Neurotoxicity Research. Oct 17. [Epub ahead of print]

Anacker, A.M.J., Loftis, J.M., Kaur, S., Ryabinin, A.E. (2010). Prairie voles as a novel model of socially-facilitated excessive drinking. Addiction Biology Jun 23. [Epub ahead of print]

Loftis, J.M., Huckans, M., Morasco, B.J. (2010). Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies. Neurobiology of Disease 37(3), pp. 519-33. (invited review).

Hauser, P., Morasco, B.J, Linke, A., Bjornson, D., Ruimy, S., Matthews, A., Rifai, M.A., Indest, D.W. & Loftis, J.M. (2009). Antiviral completion rates and sustained viral response in hepatitis C patients with- versus without- pre-existing major depressive disorder. Psychosomatics 50(5), pp. 500-5.

Loftis, J.M., Huckans, M., Ruimy, S., Hinrichs, D.J., Hauser, P.  (2008). Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1β and tumor necrosis factor-α. Neuroscience Letters 430(3):264-8.

Loftis, J.M. and Hauser, P. (2004). Interferon and Depression: A review. Journal of Affective Disorders 82(2), pp.175-190.

Marilyn Huckans, PhD

Assistant Professor of Psychiatry, Oregon Health & Science University
Staff Psychologist and Neuropsychologist, Portland VA Medical Center

Method of Contact:
Portland VA Medical Center, P3MHN
3710 SW US Veterans Hospital Road
Portland, Oregon 97239
marilyn.huckans@va.gov
Phone:  503 220-8262 ext. 54689

Education:
B.S., Human Development and Family Studies, Cornell University, 1996
Ph.D., Clinical Psychology, George Mason University, 2004
Neuropsychology Post-Doctoral Fellowship, Portland VA Medical Center, 2003-2005

Research:
Dr. Huckans’ translational research program integrates human, animal, and in vitro experiments to examine how neuroimmune factors contribute to the neuropsychiatric effects of medical, psychiatric, and substance use disorders.  Currently, she has VA and NIH funded projects that utilize neuropsychological assessment, neuroimaging, and immunological techniques to study the cognitive and psychiatric effects of methamphetamine dependence, hepatitis C, and traumatic brain injury.  Based on novel findings from her research, Dr. Huckans is also investigating immunotherapies as a potential new direction for the treatment of addictions and substance-induced cognitive and psychiatric impairments.

Clinical:
Dr. Huckans provides neuropsychological assessment, cognitive rehabilitation, and consultation services through the Neuropsychology Service at PVAMC.  Dr. Huckans most recently developed and piloted a model group-based cognitive strategies training intervention for OIF/OEF veterans with a history of traumatic brain injury and persistent mild cognitive impairment.  In an effort to move toward evidence based treatment, an adapted version of this intervention is now be evaluated through a VA-funded multi-center randomized control trial.

Teaching/Mentorship:
Dr. Huckans actively mentors and supervises graduate students and post-doctoral fellows interested in clinical and research training. As Psychology Practicum Coordinator, she coordinates clinical placements for doctoral and master’s level psychology students at PVAMC.

Activities:
Research, Education and Clinical/Service

Selected Recent Publications:
Loftis, J.M., Choi, D., Hoffman, W., & Huckans, M.S. (in press).  Methamphetamine causes persistent immune dysregulation:  A cross-species, translational report.  Neurotoxicity Research. Oct 17. [Epub ahead of print]

Huckans, M., Seelye, A., Woodhouse, J., Parcel, T., Mull, L., Schwartz, D., Mitchell, A., Lahna, D., Johnson, A., Loftis, J., Woods, S., Mitchell, S.H., and Hoffman, W.  (in press).  Discounting of delayed rewards and executive dysfunction in individuals infected with hepatitis C.  Journal of Clinical and Experimental Neuropsychology.

Schwartz, D.L., Mitchell, A.D., Lahna, D.L., Luber, H.S., Huckans, M.S., Mitchell, S.H., & Hoffman, W.H.  (2010).  Global and local morphometric differences in recently abstinent methamphetamine-dependent individuals.  Neuroimage, 50(4), 1392-401.

Loftis, J.M., Huckans, M., & Morasco, B.  (2010). Neuroimmune mechanisms of cytokine-induced depression:  Current theories and novel treatment strategies.  Neurobiology of Disease, 37(3), pp. 519-33. 

Huckans, M., Pavawalla, P., Demadura, T., Kolessar, M., Seelye, A., Twamley, E., & Storzbach, D.  (2010).  A pilot study examining effects of group-based cognitive strategy training treatment on self-reported cognitive problems, psychiatric symptoms, functioning, and compensatory strategy use in OIF/OEF combat veterans with persistent mild cognitive disorder and history of traumatic brain injury.  Journal of Rehabilitation Research and Development, 47(1), pp. 43-60.

Huckans, M., Seelye, A., Parcel, T., Mull, L., Woodhouse, J., Bjornson, D., Loftis, J.M., Morasco, B.J., Fuller, B., Sasaki, A., Storzbach, D., & Hauser, P.  (2009). The cognitive effects of hepatitis C in the presence and absence of a history of substance use disorder.  Journal of the International Neuropsychological Society, 15(1), pp.69-82. 

Research Associates and Assistants:

Starr DeGennaro, M.P.H.
Program Coordinator

Abby Buenafe, Ph.D.
Research Associate

Hannah Luber, B.A.
Study Coordinator and Neuropsychometrist

Patricia Newman, B.A.
Study Coordinator

Clare Wilhelm, Ph.D.
Research Associate

Graduate Students:

Renee Anderson, B.A.
Kristin Berggren, B.S.
Desmond Cheung, Ph.D.
Viva Wheaton, M.S.

Participants

HCV Clinical Study Coordinator

VA IRB#1682
OHSU IRB#4064
Hannah Luber, B.A.
hannah.luber@va.gov
503 220-8262 ext. 51188
Human subject referrals, scheduling questions, and other inquiries related to our hepatitis C studies should be directed here.

Methamphetamine Clinical Study Coordinator

VA IRB# 2477
OHSU IRB# 6162
Patricia Newman, B.A.
patricia.newman@va.gov
503 220-8262 ext. 58342
Human subject referrals, scheduling questions, and other inquiries related to our clinical methamphetamine studies should be directed here.

Contact Us

Program Coordinator:

Starr DeGennaro, M.P.H.
starr.degennaro@va.gov
503 220-8262 ext. 56458
General program, administrative, and IRB related inquiries should be directed here.

Laboratory Manager:

Clare Wilhelm, Ph.D.
wilhelmc@ohsu.edu
503 220-8262 ext. 54725
Inquiries regarding biological specimens and other laboratory operations should be directed here.

HCV Clinical Study Coordinator

Hannah Luber, B.A.
hannah.luber@va.gov
503 220-8262 ext. 51188
Human subject referrals, scheduling questions, and other inquiries related to our hepatitis C studies should be directed here.

Methamphetamine Clinical Study Coordinator

Patricia Newman, B.A.
patricia.newman@va.gov
503 220-8262 ext. 58342
Human subject referrals, scheduling questions, and other inquiries related to our clinical methamphetamine studies should be directed here.

Jennifer Loftis, Ph.D.

Principal Investigator
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Marilyn Huckans, Ph.D.

Principal Investigator
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