Faculty Sponsors

Grand Forks

David Bradley, Ph.D., Immunology

Additional information forthcoming

Catherine Brissette, Ph.D., Microbiology

Projects

• Role of B. burgdorferi fibronectin binding proteins in the pathogenesis of Lyme disease
• Persistence of spirochetal debris and inflammation in a rat model of neuroborreliosis

Larry Burd, M.D.

Areas of Research

• Mortality in children
• Mental health disorders
• Birth defects
• Fetal alcohol spectrum disorders
• Autism
• Sudden Infant Death Syndrome
• Mental disorders in young Children
• Prenatal alcohol exposure

Students will learn about clinical research and the application of research to office-based practice, spending several days seeing patients in addition to their project.

Archana Dhasarathy, Ph.D., Biochemistry

Area of Research

• Molecular mechanisms of cancer metastasis

Jonathan Geiger, Ph.D., Neuropharmacology

Projects

• "Role of novel endolysosome-dependent calcium regulatory mechanisms in HIV-1 associated neurocognitive disorders (HAND)"
  • The proposed studies are focused to determine novel endolysosome-dependent calcium regulatory mechanisms whereby anti-retroviral drugs (ART) and HIV-1 transactivator of transcription protein (HIV-1 Tat) contribute to the development of HAND. The central hypothesis is that ART drugs (those that elevate endolysosome pH) and HIV-1 Tat induce synaptic disruption and neuronal injury by elevating endolysosome pH and activating a novel endolysosome-dependent calcium regulatory mechanism. Guided by preliminary findings, this novel hypothesis will be tested by pursuing three specific aims: 1) determine, in vitro, the extent to which and mechanisms by which ART drugs and HIV-1 Tat activate novel endolysosome-dependent calcium regulatory mechanisms, 2) determine, in vitro, the extent to which and mechanisms by which HIV-1 Tat in the absence and presence of ART affects synaptic integrity and neuronal viability, and 3) determine, in vivo, the extent to which and mechanisms by which HIV-1 Tat in the absence and presence of ART affects synaptic integrity and neuronal injury. Dr. Geiger's lab expects to demonstrate that endolysosomes, through novel endolysosome-dependent calcium regulatory mechanisms, play a critical role in synaptic disruptions and neuronal injury that is upstream of, for example, ER and mitochondrial effects of HIV-1 Tat and ART drugs. Such expected findings will provide novel insights into the pathogenesis of HAND, and may lead to the discovery of new effective therapeutic strategies against HAND.
• "Effects of anti-retroviral drugs and HIV-1 Tat on intraneuronal accumulation of amyloid beta"
  • The proposed studies are aimed to determine the extent to which and mechanisms by HIV-1 Tat and a select series of ART drugs affect intraneuronal amyloid beta protein (Aβ) accumulation. The central hypothesis is that HIV-1 Tat and basic (but not acidic) ART drugs will lead to intraneuronal Aβ accumulation because they elevate neuronal endolysosome pH. Guided by preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) determine the extent to which and mechanisms by which HIV-1 Tat1-72 and Tat1-86 affect endolysosome morphology, function, pH, and intraneuronal Aβ accumulation in vitro, 2) determine the extent to which and mechanisms by which ART drugs alone and in combination with HIV-1 Tat affect endolysosome morphology, function, pH, and intraneuronal Aβ accumulation in vitro, and 3) determine the extent to which and mechanisms by which HIV-1 Tat and ART drugs affect intraneuronal Aβ accumulation in vivo. Results from work proposed are expected to demonstrate that elevated endolysosome pH is essential for HIV-1 Tat and ART drug-induced intraneuronal Aβ accumulation. Such results are expected to provide novel insights into the co-pathogenesis of HIV-1 associated neurocognitive disorders and Alzheimer's disease.
• "Epigenetic mechanisms regulating lasting anti-seizure effects of ketogenic diets"
  • The central hypothesis of this proposal is that ketogenic diets (KDs) can restore brain homeostasis, and that lasting effects of KD therapy are due to adenosine-mediated changes in DNA methylation. Srong preliminary data supports this innovative hypothesis, and published research from Dr. Geiger's laboratories and others provides additional evidence for antiepileptogenic properties of a KD and of adenosine. The lab's experimental approach combines complementary techniques, including metabolic profiling, electrophysiology and behavioral seizures. These experiments will be performed using state-of-the-art approaches, including long-term studies in clinically relevant animal models, and offer an unprecedented opportunity to analyze cerebral spinal fluid taken from children with pediatric epilepsy before and after treatment with a KD.

Bryon Grove, Ph.D., Cell Biology

Additional information forthcoming

Thad Rosenberger, Ph.D., Lipid Biochemistry/Neuropharmacology

Area of research

• Neuroinflammation

Fargo

Neuropsychiatric Research Institute

A division of Sanford Research, the Neuropsychiatric Research Institute was created to be a catalyst for supporting research and innovation in the science of health care, focusing on diseases and disorders of the brain and central nervous system.

Principle investigators

• James E. Mitchell, M.D.
• Stephen Wonderlich, Ph.D.
• James Roerig, PharmD
• Kristine Steffen, PharmD, Ph.D.
• Scott Engel, Ph.D.
• Ross Crosby, Ph.D.

Areas of research

• Longitudinal assessment of bariatric surgery. This is a project now in its 11th year. It involves six sites around the United States that are prospectively following a cohort of around 2,400 bariatric surgery patients. There are a number of substudies involving diabetes, heart disease, behavior, renal disease and other things as well.
• Hormonal abnormalities and sexual dysfunction in bariatric surgery patients
• Psychiatric problems and eating problems in bariatric surgery patients
• The development of alcohol use disorders after bariatric surgery
• The kinetics of alcohol after bariatric surgery
• Cognitive effects of bariatric surgery
• Pharmacokinetic changes after bariatric surgery
• Treatment collaborative for traumatized youth, a statewide treatment network to train clinicians in empirically validated therapies
• Integrative cognitive-affective therapy for binge eating disorder, a multicenter treatment study
• Ecological momentary assessment using smartphones to gather data in the natural environment

VA Health Care System

The VA is currently seeking two REMS students to assist with principle investigators conducting these summer research projects:

William Newman, M.D.

• Retrospective study: Hypoglycemia in inpatients at the Fargo VA, a 10 year perspective. Have diabetes management policies enacted made a difference?
• Retrospective study: Examine the relationship between total testosterone, free testosterone and weakly bound testosterone from a lab correlation viewpoint and also a diagnostic viewpoint.

Tze Shien Lo/Kimberly Hammer, Ph.D.

• PBP2a culture test for coagulase-negative Staphylococcus species

Tze Shien Lo/Milagros Zegarra/Kimberly Hammer, Ph.D.

• Retrospective study: Acute kidney injury and bone fracture rates associated with exposure to tenofovir in Hepatitis B patients

For more information about conducting research at the VA, contact:

Kimberly Hammer, Ph.D.
Research and Development Coordinator
Fargo VA Health Care System
Acting Research and Development Coordinator
Sioux Falls VA
Kimberly.Hammer@va.gov