Dixon Research Lab
Research Lab of Dr. Kirsty Dixon
Dr. Kirsty Dixon completed a Ph.D. at James Cook University in Townsville, Queensland, which included a research stint on the other side of the country at the University of Western Australia, Perth, investigating how the endogenous neurotrophin BDNF promotes axonal outgrowth in the cerebellum following traumatic axonal injury leading to improvements in functional recovery. She subsequently completed postdoctoral studies, at the Center for Neuroscience at the University of Melbourne and at the Miami Project to Cure Paralysis at the University of Miami, investigating how the tyrosine kinase receptors EphA4 and EphB3 (and their ephrin ligands) regulate the CNS micro-environment post-injury to inhibit axonal outgrowth and neural stem cell migration. During these positions she was successfully award a Woodside Neurotrauma Ph.D. Excellence Award, an Australian Postgraduate Award, and two travel awards.
In 2014 Dr. Dixon relocated to Virginia Commonwealth University to take up a faculty position in the Department of Physical Medicine and Rehabilitation, establishing her research laboratory whilst also performing administrative duties for the Chronic Effects of Neurotrauma Consortium (CENC). In 2016 she joined the Department of Surgery where she now directs the departments Neurotrauma Repair Laboratory investigating the brain’s response to injury and disease, with a view to developing therapies to improve outcomes. These translational studies are funded by local, state and federal research grants, and Dr. Dixon is also seeking funding for upcoming clinical trials for individuals with traumatic brain injury and Gulf War Illness (also referred to as “chronic multisymptom illness”).
OVERVIEW: The Dixon Laboratory investigates how inflammation promotes aberrant pathophysiology, with a view to developing clinically relevant therapies to improve outcomes.
- Traumatic Brain Injury (TBI)
- TBI-induced Alzheimer’s Disease
- Gulf War Illness (GWI: in collaboration with Dr. Laxmikant Deshpande). Also known as “Chronic multisymptom illness”, GWI is a multi-symptom disorder affecting many Veterans of the 1990-91 Gulf War.
- Spinal Cord Injury
INFLAMMATION AND HIPPOCAMPAL DENDRITIC PLASTICITY: Injury and disease often causes an inflammatory response in the body, which is in essence the body’s own defense mechanism. This inflammatory response includes an upregulation of inflammatory cytokines, of which a major cytokine is Tumor Necrosis Factor (TNF). The soluble form of TNF preferentially binds its receptor known as TNF Receptor 1 (TNFR1: also known as TNFRSF1A). Under physiological conditions TNFR1 can mediate beneficial homeostatic synaptic plasticity required for proper learning and memory, although under pathological conditions that promote unusually high levels of TNF, the activity of TNFR1 becomes detrimental causing impairments in neuronal long-term potentiation (LTP): the mechanism by which neural circuitry communicates. This ultimately leads to the development of impairments in hippocampal-related cognition (learning and memory), depression and neuropathic pain. To address this, the Dixon laboratory has been using a novel biologic that selectively inhibits the soluble form of the inflammatory cytokine Tumor Necrosis Factor (TNF) to prevent it from activating its receptor TNFR1. We have assessed the efficacy of this novel biologic to improve pathophysiological and functional outcomes, and now we investigate by what intracellular mechanism (i.e. ‘how’) TNFR1 activity disrupts normal neuronal activity to promote this pathophysiology. These studies are highly clinically relevant with the intent to improve the lives of individuals living with TBI and Veterans living with GWI (aka “chronic multisymptom illness”).
TBI and the MICROBIOME: We use specific probiotics to modulate gut microbiota after TBI, to improve brain pathophysiology and functional outcomes.
TBI and ALZHEIMER’S DISEASE. TBI is now a known risk factor for the later development of Alzheimer’s disease, which could be due to the persistence of TBI-induced neuroinflammation, specifically pathological levels of solTNF/TNFR1 activity. The Dixon laboratory investigates how TBI-induced solTNF/TNFR1 activity may accelerate the development of Alzheimer’s disease pathology (amyloid beta and tau pathology) leading to dendritic synaptic dysfunction that result in impaired cognition (learning and memory). https://www.yahoo.com/now/inmune-bio-inc-virginia-commonwealth-130000661.html
PANCREATITIS: Acute pancreatitis includes an inflammatory response that leads to the development of neuropathic pain. We have shown that inhibiting solTNF/TNFR1 activity prevents immune cell influx into the pancreas, which preserves pancreatic morphology and prevents the development of neuropathic pain. Studies investigating how this process is occurring are underway.
Current Lab Members
- Dr. Janakiraman Udaiyappan (Postdoctoral Fellow)
- Michelle Taylor (Ph.D. Student, Neuroscience Program)
- Nancy Nixon-Lee (Surgery Technician Extraordinaire)
- Andrew Biscardi (Medical Student Class of 2023, with VCU SoM Dean's Summer Research Fellowship)
Past Lab Members
- Diane Ingabire (Ph.D. Rotation)
- Elizabeth Geisler (Ph.D. Rotation)
- Michelle Taylor (Ph.D. Rotation)
- Katelyn Larson (Lab Technician)
- Celine Ashbury (Lab Technician)
- Melissa Damon (Lab Technician)
- Kathryn Nguyen (Medical Student, Class of 2022, with VCU SoM Dean's Summer Research Fellowship)
- Dr. Naime Rihane (Postdoctoral Fellow)
- Monika Radhika (Lab Technician)
- Rajasa Randhi (Lab Technician)
Past Lab Members (Undergraduate course work)
- Marjoya Smith (HPEX 395 course)
- Megan Enos (HPEX 395 course)
- Alyssa Raney (HPEX 395 course)
Selected Publications and Press Releases
- 2022: XPro1595 decreases development of Alzheimer pathology (amyloid beta and tau) following TBI (22nd December)
- 2021: Dr. Kirsty Dixon establishes partnership with biotech company INmuneBio to treat inflammation and brain injuries
- 2016: Dr. Kirsty Dixon invited and hosted U.S. Congressman Jerry McNerney to visit VCU and the McGuire VA to learn about the TBI research programs.
Selected Peer-Reviewed Publications
- Janakiraman, U., Larson, K., Nixon-Lee, N., Damon, M., Biscardi, A., Hawkins, E., Deshpande, L.S. and Dixon, K.J. (2022). SELECTIVE INHIBITION OF SOLUBLE TNF ATTENUATES HIPPOCAMPAL NEUROINFLAMMATION AND PSD-95 EXPRESSION TO IMPROVE NEUROLOGICAL FUNCTIONS IN A RAT MODEL OF GULF WAR ILLNESS. bioRxiv pre-print, 2022.2011.2028.518204. https://www.biorxiv.org/content/biorxiv/early/2022/11/28/2022.11.28.518204.full.pdf
- Larson, K., Damon M., Randhi R., Nixon-Lee N., and Dixon K.J., Selective inhibition of soluble TNF using XPro1595 improves hippocampal pathology to promote improved neurological recovery following traumatic brain injury in mice (2022) CNS & Neurological Disorders: Drug Targets Jun 10. Doi: 10.2174/1871527321666220610104908. PMID: 35692164. https://pubmed.ncbi.nlm.nih.gov/35692164/
- Randhi R., Damon M., and Dixon K.J., Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice. (2021) BMC Gastroenterology 21:243. PMID: 34049483. https://pubmed.ncbi.nlm.nih.gov/34049483/
- Wang, C., Yang, J., Z., H., Guo, Q., Wu, X., Bradley, J., Peberdy, M.A., Ornato, J., Dixon, K.J. and Tang, W. XPro1595 reduces the severity of post resuscitation myocardial dysfunction in a rat model of cardiac arrest. (2018) Circulation, 138:A321.
- Dixon K.J., (2017) Pathophysiology of Traumatic Brain Injury. Physical Medicine and Rehabilitation Clinics of North America, 28(2):215-25. PMID 28390509. https://pubmed.ncbi.nlm.nih.gov/28390509/
- Department of Defense CDMRP PRARP IIRA (PI: Dixon) $750,000, PENDING
- Investigating the intersection between ApoE4, TBI and AD. Collaboration with Dr. Elliott Mufson at Barrow Neurological Institute.
- Agricultural Research Service/Department of Agriculture (Subaward, PI: Dixon)
- Identifying the efficacy of chemically-treated gauze pads to ‘stop the bleeding’.
- VCU CCTR Endowment Fund pilot grant (PI: Dixon) $50,000
- Investigating the intersection of TBI and AD on microglial phagocytosis and neuronal cell death.
- VCU PMDC Pilot Grant Program (PI: Dixon) $50,000
- Investigating the intersection between ApoE4 and TBI on astrocytic phagocytosis of synaptic debri.
- Virginia Center on Aging: ARDRAF (PI: Dixon) $45,000
- Investigating mechanisms underlying the intersection of TBI and AD on hippocampal dendritic plasticity and associated functional impairment.
- Department of Defense CDMRP GWIRP (PI: Dixon) $775,000
- Investigating a novel treatment strategy for individuals with GWI to improve hippocampal brain pathology resulting in a reversal of neurological impairments. Collaboration with Dr. Laxmikant Deshpande in VCU Department of Neurology.
- Department of Defense BAAEMC (PI: Mangino; Co-I: Dixon)
- Assessing the efficacy of PEG20K to improve outcomes following TBI.
- Department of Defense CDMRP SCIRP TRA (PI: Mangino; Co-I: Dixon)
- Assessing the efficacy of PEG20K to improve outcomes following spinal cord injury.
- Virginia Department of Aging and Rehabilitative Services: Commonwealth Neurotrauma Initiative (PI: Dixon) $450,000
- Investigating neuro-inflammatory mechanisms of novel therapies that alleviate chronic pain following TBI.
- VCU Department of Surgery Pilot Grant Program (PI: Dixon) $25,000
- Examining the role of TNFR1 to improve pathology and alleviate neuropathic pain during pancreatitis.
- Dr. Kirsty Dixon invited to present at the 13th Annual Traumatic Brain Injury Conference in Washington DC on June 19-20th 2023.
- NCA TBI symposium
- Michelle Taylor’s abstract for oral presentation accepted
- Dr. Janakiraman Udaiyappan’s abstract for poster presentation accepted
- Society of Toxicology Annual Meeting
- Dr. Janakiraman Udaiyappan’s abstract for poster presentation accepted
- AD/PD 2023 (International Conference on Alzheimer’s and Parkin’s Diseases and related neurological disorders
- Michelle Taylor’s abstract for poster presentation accepted
- Dr. Kirsty Dixon is PI on DoD clinical trial grant application partnering with INmuneBio to study the effects of XPro1595 in patients with TBI at VCUHS.
- Press Release on Dixon Lab for upcoming DoD funded TBI-AD studies https://www.yahoo.com/now/inmune-bio-inc-virginia-commonwealth-130000661.html
- Congratulations to former lab technician Katelyn Larson for getting accepted into the VCU’s Medical Laboratory Science Master of Science, categorical concentration in clinical chemistry!! Good luck!
- Congratulations to our former lab volunteer Larissa Diaz for being accepted into medical school. Big achievement!
- High school student Harini Venkateswaran volunteers in the Dixon laboratory over summer to observe translational research activities.
- VCU Department of Surgery Research Day
- Dr. Janakiraman Udaiyappan’s abstract for oral presentation accepted.
- Michelle Taylor joins the Dixon laboratory as a Ph.D. candidate in VCU’s prestigious Neuroscience Ph.D. program.
- VCU SOM School of Medicine Medical Student Research Day
- Andrew Biscardi presents poster “Structural changes in brain MRI associated with gulf war illness and effects of solTNF/TNFR1 inhibition”.
- VCU Anatomy and Neurobiology Departmental Trainee Symposium on 6th May
- Congratulations to Dr. Janakiraman Udaiyappan for winning the “Speaker Award”.
- VCU School of Medicine Medical Student Research Day
- Andrew Biscardi presents poster “Optimizing in-vivo strategies to assess c
- Elizabeth (Liz) Geisler undertakes Ph.D. rotation in the Dixon laboratory.
- Diana Ingabire undertakes Ph.D. rotation in the Dixon laboratory.
- Michelle Taylor undertakes Ph.D. rotation in the Dixon laboratory.
- The Dixon laboratory welcomes Dr. Janakiraman Udaiyappan (postdoctoral fellow).
- Congratulations Andrew Biscardi for being awarded a prestigious VCU SOM Dean’s Summer Research Fellowship to perform research in the Dixon laboratory.
- NCA TBI symposium
- Dr. Kirsty Dixon presentation “Soluble TNF Inhibitor XPro1595 Attenuates Secondary Inflammatory Response to Improve Outcomes Following TBI”
- The Dixon laboratory welcomes Andrew Biscardi (first year VCU medical student) to volunteer on research projects.
- Andrew Biscardi (first year medical student) joins the Dixon lab. Welcome.
- Military Health System Research Symposium
- Dr. Kirsty Dixon invited as only 1 of 8 speakers to present in the TBI session. “XPro1595 improves hippocampal pathology and associated neurological outcomes following TBI”.
- Congratulations Kathryn Nguyen for being awarded a prestigious VCU SOM Dean’s Summer Research Fellowship to perform research in the Dixon laboratory.
- VCU Department of Pharmacology and Toxicology: TRIPN Symposium
- Dr. Kirsty Dixon invited to present “solTNF Inhibitor as a Novel Therapy to Improve Outcomes following TBI”.
- Larissa Diaz completes summer volunteer position in the Dixon lab.
- The Dixon lab hosts half-day workshop on “Brain Anatomy” for Girl Scouts “Women in Science” Day.
- See the VCU jobs site for any openings.
- The VCU CCTR will fund undergraduate research fellowship awards for clinical translational research projects focused on human health and mentored by a VCU faculty member. Each fellowship award includes $1500 in funding for the student and $500 for the faculty mentor. For details and to apply visit: https://provost.vcu.edu/initiatives/urop/cctr/
- You First will fund undergraduate research fellowship awards for research projects mentored by VCU faculty focused on diversity, underrepresented perspectives, student success barriers (social, academic, and financial), new approaches and innovations to enhancing student success, faculty engagement, and teaching/learning approaches. Each fellowship award includes $1500 in funding for the student and $500 for the faculty mentor. For details and to apply visit: https://provost.vcu.edu/initiatives/urop/youfirst/
- Undergraduate Research and Creative Scholarship Summer Fellowships (UROP): Fund a variety of undergraduate student fellowship awards for projects in any discipline, mentored by VCU faculty. Successful student applicants will receive funding support in the amount of $1,500 and $500 for the faculty mentor. Applicants must submit an online application no later than March 14, 2023 for review. For details and to apply visit: https://provost.vcu.edu/initiatives/urop/urop-fellowship/
- Contact Dr. Sarah Golding (VCU Director of Undergraduate Research) for additional undergraduate student fellowship opportunities.
- VCU SOM Dean’s Summer Research Fellowship: For current first-year VCU medical students to conduct funded research during the summer between years M1 and M2. Applicants must complete the School of Medicine Student Summer Research Fellowship Application form.