Jacqueline Renee Kulbe

Transcription

1 Jacqueline Renee Kulbe Doctoral Candidate Department of Neuroscience Spinal Cord & Brain Injury Research Center MD-PhD Program, University of Kentucky College of Medicine Education University of Kentucky College of Medicine, Lexington, KY Clinical and Translational Sciences Certificate Program Doctor of Philosophy Department of Neuroscience Spinal Cord & Brain Injury Research Center Doctor of Medicine Promoted with High Distinction ( ) Promoted with High Distinction ( ) Present Present Present University of Denver, Denver, CO Bachelor of Science in Biology Magna cum laude, Phi Beta Kappa Minors in chemistry and mathematics University of Colorado, Denver, CO Research Experience Graduate Research Assistant (with Edward Hall, PhD) University of Kentucky College of Medicine, Lexington, KY Department of Neuroscience, Spinal Cord & Brain Injury Research Center Present Dissertation Project: Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Inhibition of Mitochondrial Permeability Transition, Lipid Peroxidation, or Monoamine Oxidase Evaluation of the ability of cyclosporine A to improve synaptic and non-synaptic mitochondrial bioenergetics 24h following severe controlled cortical impact injury in rats

2 Evaluation of the ability of a 72h subcutaneous continuous infusion of cyclosporine A, phenelzine, and the combination to improve mitochondrial respiratory function, decrease formation of protein-aldehyde conjugates, and attenuate cytoskeletal degradation following severe controlled cortical impact injury in rats Comparison of the effects of phenelzine (aldehyde scavenger, monoamine oxidase inhibitor), hydralazine (aldehyde scavenger, non-monoamine oxidase inhibitor), and pargyline (non-aldehyde scavenger, monoamine oxidase inhibitor) on cognitive impairment and cortical tissue sparing following severe controlled cortical impact injury in rats MD/PhD Research Rotation (with James Geddes, PhD) 2014 University of Kentucky College of Medicine, Lexington, KY Department of Neuroscience, Spinal Cord & Brain Injury Research Center Project: Identification of Novel Serum Biomarkers of Mild Traumatic Brain Injury Using Phage Display Used serum collected from mice that sustained repetitive mild closed head injuries and rats that sustained mild lateral fluid percussion injuries in an attempt to identify recombinant phages that preferentially bind proteins in injured serum using a subtractive panning technique MD/PhD Summer Research Rotation (with Patrick Sullivan, PhD) 2012 University of Kentucky College of Medicine, Lexington, KY Department of Neuroscience, Spinal Cord & Brain Injury Research Center Project: Does the mitochondrial protein mitoneet play a direct role in traumatic brain injury? Worked closely with a doctoral candidate to assess the effect of mitoneet agonists NL- 1 and pioglitazone (PPARδ-independent mechanism) and transgenic knockout of mitoneet on behavior following moderate controlled cortical impact injury Assisted in behavioral assessments post-injury: beam walk in mice and Morris water maze in rats Professional Research Assistant (with Ulli Bayer, PhD) University of Colorado Denver School of Medicine, Denver, CO Department of Pharmacology Project: The role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in excitotoxicity, molecular memory and synaptic plasticity; The role of autophagy in excitotoxic stimulus of dissociated hippocampal neurons

3 Investigated the effect of excitotoxicity and the CaMKII inhibitor tatcn21 on autophagy, and the effect of induction and inhibition of autophagy on excitotoxic neuronal death Studied the effect of various CaMKII mutations on neuronal survival and synaptic plasticity through knockdown / re-expression / over-expression during various cellular treatments Examined substrate dependent activity of auto-phosphorylated versus stimulated CaMKII Biological Research Technician (with Kim Heidenreich, PhD) University of Colorado Denver School of Medicine, Denver, CO Department of Pharmacology Project: In-vitro mechanisms of programmed cellular death in chronic neurodegeneration and acute traumatic brain injury Induced apoptosis in dopamine neurons and autophagy in Purkinje neurons via pharmacological insult and trophic factor withdrawal and attempted rescue using various growth factors Live imaging of the autophagosome and lysosome during autophagic death of Purkinje neurons Examined mitochondrial fission and fusion occurring during apoptosis in cerebellar granular neurons Peer Reviewed Publications 1. Hill RL, Kulbe JR, Singh IN, Wang JA, Hall ED. Synaptic mitochondria are more susceptible to traumatic brain injury-induced oxidative damage and respiratory dysfunction than non-synaptic mitochondria. Neuroscience 386: (2018) 2. Kulbe JR, Singh IN, Wang JA, Cebak JE, Hall ED. Continuous infusion of phenelzine, cyclosporine A, or theirncombination: evaluation of mitochondrial respiration, oxidative damage, and spectrin degradation following severe controlled cortical impact injury. J Neurotrauma 35(11): (2018) 3. Kulbe JR, Hill RL, Singh IN, Wang JA, Hall ED. Synaptic mitochondria sustain more damage than non-synaptic mitochondria following traumatic brain injury and are protected by cyclosporine A. J Neurotrauma 34(7): (2017) 4. Barcomb K, Buard I, Coultrap SJ, Kulbe JR, O'Leary H, Benke TA, Bayer KU. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. FASEB J 28: (2014)

4 5. Kulbe JR, Mulcahy Levy JM, Coultrap SJ, Thorburn A, Bayern KU. Excitotoxic glutamate insults block autophagic flux in hippocampal neurons. Brain Res 1542: (2014) 6. Coultrap SJ, Buard I, Kulbe JR, Dell'Acqua ML, Bayer KU. CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin. J Biol Chem 285: (2010) Review Articles and Book Chapters 1. Kulbe JR and Hall ED. Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology. Prog Neurobiol 158: (2017) Review 2. Cebak JE, Singh IN, Wang JA, Hill RL, Kulbe JR, Hall ED. Carbonyl scavenging as an antioxidant neuroprotective strategy for acute traumatic brain injury, in New Therapeutics for Traumatic Brain Injury: Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration, Heidenreich KA (ed.), Academic Press (2016) Book chapter 3. Kulbe JR and Geddes JW. Current status of fluid biomarkers in mild traumatic brain injury. Exp Neurol 375: (2016) Review Acknowledgements 1. Coultrap SJ, Bayer KU. Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). J Biol Chem 289: (2014) 2. Coultrap SJ, Barcomb K, Bayer KU. A significant but rather mild contribution of T286 autophosphorylation to Ca2+/CaM-stimulated CaMKII activity. PLoS One 7: e37176 (2012) 3. O'Leary H, Liu WH, Rorabaugh JM, Coultrap SJ, Bayer KU. Nucleotides and phosphorylation bi-directionally modulate Ca2+/calmodulin-dependent protein kinase II (CaMKII) binding to the N-methyl-D-aspartate (NMDA) receptor subunit GluN2B. J Biol Chem 286: (2011) 4. Coultrap SJ, Bayer KU. Improving a natural CaMKII inhibitor by random and rational design. PLoS One 6: e25245 (2011)

5 National Posters and Abstracts 1. Kulbe JR, Singh IN, Dunkerson JA, Wang JA, Huettl PF, Hill RL, Smith R, and Hall ED Neuroprotective Strategies following experimental traumatic brain injury: inhibition of permeability transition, lipid-peroxidation derived aldehyde scavenging, and monoamine oxidase inhibition Poster presented at 48 th Annual Society for Neuroscience Meeting, San Diego, CA (2018). Program No Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, Online. 2. Kulbe JR, Singh IN, Dunkerson JA, Wang JA, Cebak JE, Hill RL, Smith R, Huettl P, and Hall ED A pharmacologic neuroprotective approach to experimental TBI: targeting mitochondria & lipid peroxidation-derived aldehydes Poster presented at 3 rd Joint Symposium of the International and National Neurotrauma Societies, Toronto, Canada (2018). Journal of Neurotrauma: 35: PS (2018) 3. Kulbe JR, Singh IN, Dunkerson J, Wang JA, Cebak JE, Hill RL, Smith R, Huettl P, and Hall ED A pharmacologic neuroprotective approach to severe traumatic brain injury: targeting mitochondria and lipid peroxidation Poster presented at AAP/ASCI/APSA 2018 Joint Meeting, Chicago, IL (2018) 4. Kulbe JR, Singh IN, Cebak JE, Wang JA, and Hall ED Neuroprotective strategies following severe controlled impact traumatic brain injury: lipid peroxidation-derived neurotoxic aldehyde scavenging and inhibition of mitochondrial permeability transition Poster at 47 th Annual Society for Neuroscience Meeting, Washington, DC (2017). Program No Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, Online. 5. Kulbe JR, Singh IN, Cebak JE, Wang JA, and Hall ED Neuroprotective evaluation of the combination phenelzine and cyclosporine A following severe controlled cortical impact traumatic brain injury Poster presented at 35 th Annual National Neurotrauma Symposium, Snowbird, UT (2017). Journal of Neurotrauma: 34: A-1-A-164 (2017) 6. Hill RL, Singh IN, Wang JA, Kulbe JR, Hall ED Phenelzine administration following traumatic brain injury improves synaptic and non-synaptic mitochondrial respiratory function Poster at 35 th Annual National Neurotrauma Symposium, Snowbird, UT (2017). Journal of Neurotrauma: 34: A-1-A-164 (2017) 7. Kulbe JR, Singh IN, Wang JA, and Hall ED Evaluation of the combinational therapy cyclosporine A and phenelzine on protection of mitochondria following severe controlled cortical impact injury Poster presented at AAP/ASCI/APSA 2017 Joint Meeting, Chicago, IL (2017)

6 8. Kulbe JR, Hill RL, Singh IN, Wang JA, and Hall ED Cyclosporine A protects synaptic and non- synaptic mitochondria following severe controlled cortical impact injury in rats Poster presented at 34 th Annual National Neurotrauma Symposium, Lexington, KY (2016). Journal of Neurotrauma: 33(13): A-1-A-139 (2016) 9. Hill RL, Singh IN, Wang JA, Kulbe JR, and Hall ED Differing time courses of synaptic & non- synaptic mitochondrial dysfunction & oxidative damage following TBI in young adult males Poster at 34 th Annual National Neurotrauma Symposium, Lexington, KY (2016). Journal of Neurotrauma: 33(13): A-1-A-139 (2016) 10. Kulbe JR, Hill RL, Singh IN, Wang JA, and Hall ED Temporal profile of non-synaptic and synaptic mitochondrial bioenergetics following severe controlled cortical impact traumatic brain injury in rats Poster presented at 3 rd Annual Molecular Psychiatry Meeting, San Francisco, CA (2015) Regional, Local, Institutional Posters and Abstracts 1. Kulbe JR, Singh IN, Dunkerson J, Wang JA, Hill RL, Smith R, Huettl P, and Hall ED Neuroprotective strategies following severe controlled impact traumatic brain injury: lipid peroxidation-derived neurotoxic aldehyde scavenging and inhibition of mitochondrial permeability transition Poster presented at 24 th Annual KSCHIRT Symposium, Lexington, KY (2018) 2. Kulbe JR, Singh IN, Dunkerson J, Wang JA, Hill RL, Smith R, Huettl P, and Hall ED Neuroprotective strategies following severe controlled impact traumatic brain injury: lipid peroxidation-derived neurotoxic aldehyde scavenging and inhibition of mitochondrial permeability transition Poster presented at 13 th Annual Center for Clinical and Translational Sciences Spring Conference, Lexington, KY (2018) 3. Kulbe JR, Singh IN, Wang JA, and Hall ED Neuroprotective evaluation of the combination phenelzine and cyclosporine A following severe controlled cortical impact traumatic brain injury Poster presented at 23 rd Annual KSCHIRT Symposium, Louisville, KY (2017) 4. Kulbe JR, Singh IN, Wang JA, and Hall ED Evaluation of the combinational therapy cyclosporine A and phenelzine on protection of mitochondrial respiratory function following severe controlled cortical impact injury in rats Poster presented at 12 th Annual Center for Clinical and Translational Sciences Spring Conference, Lexington, KY (2017) 5. Kulbe JR, Hill RL, Singh IN, Wang JA, and Hall ED Cyclosporine A protects synaptic and non- synaptic mitochondria following severe controlled cortical impact injury in rats Poster at Kentucky Neuroscience Institute Clinical-Translational Research Symposium, Lexington, KY (2016)

7 6. Kulbe JR, Hill RL, Singh IN, Wang JA, and Hall ED Cyclosporine A protects synaptic and non-synaptic mitochondrial bioenergetics 24h following severe controlled cortical impact injury Poster presented at 31 st Annual Bluegrass Society for Neuroscience Spring Neuroscience Research Day, Lexington, KY (2016) 7. Kulbe JR, Hill RL, Singh IN, Wang JA, and Hall ED Cyclosporine A protects synaptic and non-synaptic mitochondria and attenuates calpain-mediated cytoskeletal degradation 24h following severe controlled cortical impact traumatic brain injury in rats Poster presented at University of Kentucky AOA Groves Memorial MD/PhD Student Research Day, Lexington, KY (2016) 8. Kulbe JR and Geddes JW Identification of novel serum biomarkers for mild traumatic brain injury using phage display Poster presented at University of Kentucky AOA Groves Memorial MD/PhD Student Research Day, Lexington, KY (2015) 9. Kulbe JR, Mulcahy Levy JM, Coultrap SJ, Thorburn A, and Bayer KU Excitotoxic glutamate insults block autophagic flux in hippocampal neurons Poster presented at University of Kentucky AOA Groves Memorial MD/PhD Student Research Day, Lexington, KY (2014) 10. Kulbe JR, Mulcahy Levy JM, Coultrap SJ, Thorburn A, and Bayer KU Excitotoxic glutamate insults block autophagic flux in hippocampal neurons Poster presented at University of Kentucky AOA Groves Memorial MD/PhD Student Research Day, Lexington, KY (2013) Oral Conference Presentations 1. A pharmacologic neuroprotective approach to experimental TBI: targeting mitochondria & lipid peroxidation-derived aldehydes 3 rd Annual Neuroscience Clinical-Translational Research Symposium, Lexington, KY (2018) 2. Multi-Mechanistic Attenuation of Mitochondrial Dysfunction and Lipid Peroxidation Following Experimental Traumatic Brain Injury 13 th Annual Center for Clinical and Translational Sciences Spring Conference, Lexington, KY (2018) 3. Continuous Infusion of Phenelzine, Cyclosporine A, or the Combination: Evaluation of Mitochondrial Bioenergetics, Oxidative Damage, and Cytoskeletal Degradation Following Severe Cortical Impact Traumatic Brain Injury in Rats 2 nd Annual University of Michigan Massey TBI Summit Invited Mentee Research Presentation, Ann Arbor, MI (2017) 4. Cyclosporine A Protects Synaptic Mitochondria Following TBI, NIMH MD/PhD Student Conference Data Blitz, San Francisco, CA (2015)

8 Oral Department Presentations 1. Multi-Mechanistic Attenuation of Mitochondrial Dysfunction and Lipid Peroxidation Following Experimental Traumatic Brain Injury Center for Clinical and Translational Sciences Seminar, University of Kentucky, Lexington, KY (2018) 2. Neuroprotective Evaluation of 72h Subcutaneous Continuous Infusion of Phenelzine, Cyclosporine A, and the Combination Following Severe Controlled Cortical Impact Injury Department of Neuroscience Seminar, University of Kentucky, Lexington, KY (2017) 3. Cyclosporine A Improves Synaptic and Non-Synaptic Mitochondrial Respiration following TBI, Department of Neuroscience Seminar, University of Kentucky, Lexington, KY (2016) 4. Identification of Novel Serum Biomarkers for Mild Traumatic Brain Injury Using Phage Display, Center for Clinical and Translational Sciences Seminar, University of Kentucky, Lexington, KY (2015) Journal Club Presentations 1. Journal Club Paper Presentation: Cyclic head rotations produce modest brain injury in infant piglets (Coats et al. 2016), University of Kentucky Spinal Cord and Brian Injury Research Center Journal Club, Lexington, KY (2016) 2. Journal Club Paper Presentation: Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury (Ojo et al. 2014), University of Kentucky Spinal Cord and Brian Injury Research Center Journal Club, Lexington, KY (2016) Course Lectures Chronic traumatic encephalopathy-integration of canonical traumatic brain injury 2018 secondary injury mechanisms with tau pathology ANA 605 / PGY605 Neurobiology of CNS Injury and Repair, University of Kentucky Programmed Cell Death Mechanisms: Role in CNS Injury 2018 ANA 605 / PGY605 Neurobiology of CNS Injury and Repair, University of Kentucky Programmed Cell Death Mechanisms: Role in CNS Injury 2016 ANA 605 / PGY605 Neurobiology of CNS Injury and Repair, University of Kentucky

9 Funding NIH F30 (NINDS) NRSA pre-doctoral Fellowship (F30NS096876) 07/ Present Multi-mechanistic protection of mitochondria following traumatic brain injury Kentucky Spinal Cord and Head Injury Trust Fellowship University of Kentucky MD/PhD Fellowship Present Present Honors & Awards University of Kentucky Graduate School Incentive Award 2018 Awarded for receipt of a nationally competitive fellowship, i.e. NRSA F30 Society for Neuroscience Trainee Professional Development Award 2018 Awarded to attend the 2018 Society for Neuroscience Annual Meeting, San Diego, CA University of Kentucky Graduate School Travel Award 2018 Awarded to attend the 3 rd Joint Symposium of the International and National Neurotrauma Societies, Toronto, Canada 2 nd Annual University of Michigan Massey TBI Summit Invited Mentee 2017 Invited mentee, Ann Arbor, MI EMBO-FEBS Lecture Course Mitochondria in Life, Death, and Disease 2017 Selected attendee, Brindisi, Italy National Neurotrauma Symposium Sensor Travel Grant Award 2017 Awarded to attend the Environmental Sensor Use for Quantifying Neural Exposure to Inertial and Blast Forces Pre-Meeting Workshop, 35 th Annual National Neurotrauma Symposium, Snowbird, UT University of Kentucky Graduate School Travel Award 2017 Awarded to attend the 2017 AAP/ASCI/APSA Joint Meeting, Chicago, IL University of Kentucky Graduate School Incentive Award 2016 Awarded for receipt of a nationally competitive fellowship, i.e. NRSA F30 AUPN/NINDS Travel Award 2016 Awarded to attend the Combining Clinical and Research Careers in Neuroscience Symposium, Washington, DC

10 Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT) Travel Award 2016 Awarded to attend the 34 th Annual National Neurotrauma Symposium, Lexington, KY NIMH Travel Award 2015 Awarded to attend the NIMH MD/PhD Student Conference & 3 rd Annual Molecular Psychiatry Meeting, San Francisco, CA University of Kentucky College of Medicine (M1 and M2) Promoted with High Distinction Promoted with High Distinction Highest Academic Achievement: Behavioral Basis of Medicine 2013 Distinguished Portfolio Award: Introduction to Clinical Medicine I 2013 Undergraduate Magna cum laude Phi Beta Kappa Alpha Epsilon Delta and Golden Key National Honor Societies Dean s List, National Dean s List and Hornbeck Scholar Outstanding Student Achievement, Department of Chemistry Institutional Service University of Kentucky MD-PhD Internal Advisory Committee Ad hoc reviewer Headache: The Journal of Head and Face Pain Mentoring Sahana Holla, High School Student 2017 Model Lab High School Literature Research Project, Medicine: The Future is in the Past Teaching Assistantship Neuroscience Department Proctor (Principles of Human Anatomy) Present Neuroscience Department Proctor (Anatomy & Physiology for Nursing) Neuroscience Department Teaching Assistant (Anatomy & Physiology for Nursing) Neuroscience Department Proctor (Principles of Human Anatomy)

11 Membership Society for Neuroscience Present American Physician Scientist Association Present National Neurotrauma Society Present Women in Neurotrauma Research Present Bluegrass Chapter of the Society for Neuroscience Present American Medical Student Association