Kyle Fink, Ph.D.

Kyle Fink, Ph.D.

Assistant Adjunct Professor
Neurology and Institute for Regenerative Cures

Stem Cell Program
2921 Stockton Blvd., Room 1300
Sacramento, CA 95817
(916) 703-9300

 

Research Interests

Dr. Fink received his Ph.D. in Neuroscience from Central Michigan University and the University of Nantes. He has focused on therapeutic development for neurodegenerative diseases, brain injury, and some forms of brain cancer. His research team focuses on genetically-linked neurological disorders such as CDKL5 deficiency (rare intractable pediatric epilepsy), Angelman’s Syndrome, and Huntington’s disease that are targetable with gene editing molecules in addition to some forms of brain cancer. His lab is identifying candidate sequences through whole genome sequencing and transcriptomics using a bioinformatics approach for structural variation discovery and genotyping that identify underlying common genetic variants. Gene variants linked to disease phenotype are examined for “actionable domains” for which we create therapeutic artificial transcription factors. Patient-derived samples can be used to create in vitro neuronal disease-in-a-dish models using novel induced neuron techniques. His team builds on the existing strengths and expertise at UC Davis and utilizes the necessary resources to develop a therapeutic pipeline in which precision medicine can be used to identify novel disease causing genetic variants to advance Precision Neurotherapeutics to clinical applications.

His current research focuses on two major goals 1) The therapeutic application of transcription activator-like effector (TALE) and clustered regularly interspaced short palindrome repeats (CRISPR) to modify gene expression in genetically-linked pediatric neurological diseases; and 2) the development of delivery systems that can safely and efficaciously target the central nervous system with our novel gene editing platforms. These goals specifically address: A) how to deliver these potent therapeutics to maximize the biodistribution in the central nervous system; B) how to increase the specificity of each construct to limiting off-target effects; and C) how to minimize the immune response to increase safety and the therapeutic potential of this approach. They have used known information regarding JHD and CDKL5 deficiency to guide construction of potent, precise gene modifying modalities- CRISPR/Cas9 and TALE. These platforms can turn on or enhance transcription of a gene, transcriptionally silence expression, cause permanent epigenetic changes, or remove a piece of DNA via targeted double stranded breaks essentially allowing for custom modifications to be made at the genomic level.

Education

University of California, Davis, Medical Center, Stem Cell Program
Sacramento, California
Ruth L. Kirchstein NRSA Postdoctoral Scholar, Institute for Regenerative Cures, Stem Cell Program, 2016

University of Nantes
Nantes, France
Ph.D., Neuroscience, INSERM UMR643, 2013

Central Michigan University
Mount Pleasant, Michigan
Ph.D., Neuroscience, Field Neurosciences Institute of Restorative Neurology, 2013

Central Michigan University
Mount Pleasant, Michigan
M.S., Experimental Psychology, 2010

University of Portland
Portland, Oregon
B.A., Psychology with Neuroscience Focus, The BRAIN Lab, 2008

Professional Memberships

National Neurotrauma Society

World Congress on Huntington’s Disease

Society for Neuroscience

American Society for Neural Therapy and Repair

Huntington’s Study Group

Faculty for Undergraduate Neuroscience

Huntington’s Outreach Project for Education (HOPES)

American Society for Neural Therapy and Repair Planning Committee

International Society for Stem Cell Research

Frontiers in Neuroscience, Topics Editor

Recent Publications

Deng P, Torrest A, Pollock K, Dahlenburg H, Annett G, Nolta JA, Fink KD. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells. Neural Regen Res. 2016 May;11(5):702-5. doi: 10.4103/1673-5374.182682. Review PMID: 27335539

Deng P, Anderson JD, Yu AS, Annett G, Fink KD, Nolta JA. Engineered BDNF producing cells as a potential treatment for neurologic disease. Expert Opin Biol Ther. 2016 Aug;16(8):1025-33. doi: 10. Fink KD 1080/14712598.2016.1183641. Epub 2016 May 21. PMID: 27159050

Fink KD, Deng P, Gutierrez J, Anderson JS, Torrest A, Komarla A, Kalomoiris S, Cary W, Anderson JD, Gruenloh W, Duffy A, Tempkin T, Annett G, Wheelock V, Segal DJ, Nolta JA. Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts. Cell Transplant. 2016;25(4):677-86. doi: 10.3727/096368916X690863. Epub 2016 Feb 4. PMID: 26850319

Matchynski-Franks JJ, Pappas C, Rossignol J, Reinke T, Fink K, Crane A, Twite A, Lowrance SA, Song C, Dunbar GL Mesenchymal Stem Cells as Treatment for Behavioral Deficits and Neuropathology in the 5xFAD Mouse Model of Alzheimer's Disease. Cell Transplant. 2016;25(4):687-703. doi: 10.3727/096368916X690818. Epub 2016 Feb 2. PMID: 26850119

Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, Montgomery EN, Mellema MS, Bardini RL, Contreras Z, Hoon M, Bauer G, Fink KD, Fury B, Hendrix KJ, Chedin F, El-Andaloussi S, Hwang B, Mulligan MS, Lehtiö J, Nolta JA. Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling. Stem Cells. 2016 Mar;34(3):601-13. doi: 10.1002/stem.2298. Epub 2016 Feb 19.PMID: 26782178

Pollock K, Dahlenburg H, Nelson H, Fink KD, Cary W, Hendrix K, Annett G, Torrest A, Deng P, Gutierrez J, Nacey C, Pepper K, Kalomoiris S, D Anderson J, McGee J, Gruenloh W, Fury B, Bauer G, Duffy A, Tempkin T, Wheelock V, Nolta JA. Human Mesenchymal Stem Cells Genetically Engineered to Overexpress Brain-derived Neurotrophic Factor Improve Outcomes in Huntington's Disease Mouse Models. Mol Ther. 2016 May;24(5):965-77. doi: 10.1038/mt.2016.12. Epub 2016 Jan 14. PMID: 26765769

Fink K.D., Deng P, Torrest A, Stewart H, Pollock K, Gruenloh W, Annett G, Tempkin T, Wheelock V, and Nolta J.A. Developing Stem Cell Therapies for Juvenile and Adult onset Huntington’s disease. Regen Med. 2015;10(5):623-46. doi: 10.2217/rme.15.25. Review. PMID: 26237705

Rossignol, J,* Fink, K.D.,* Crane, A, Davis, K.K., Bombar, M.C., Clerc, S., Bavar, A.M., Lowrance, S.A., Song, C., Witte, S.J.., Lescaudron, L., and Dunbar, G.L. Reductions in Behavioral Deficits and Neuropathology in the R6/2 Mouse Model of Huntington’s disease following Transplantation of Bone-Marrow-Derived Mesenchymal Stem Cells is Dependent on Passage Number. Stem Cell Res Ther. 2015 Feb 19;6:9. doi: 10.1186/scrt545.PMID: 25971780

Dunkerson, J., Moritz, K.E., Young, J., Pionk, T., Fink, K.D., Rossignol, J., Dunbar, G.L., and Smith, J.S. Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury. Restor Neurol Neurosci. 2014;32(5):675-87. doi: 10.3233/RNN-140408.PMID: 25079980

Rossignol, J., Crane, A.T., Fink, K.D., Dunbar, G.L. Will Undifferentiated Induced Pluripotent Stem Cells Ever have Clinical Utility? J Stem Cell Res Ther. 4:189. doi:10.4172/2157-7633.1000189

Fink, K.D., Crane, A.T., Lévêque, X., Dues, D.J., Huffman, L.D., Moore, A.C., Story, D.T., DeJonge, R.E., Antcliff, A., Starski, P.A., Lu, M., Lescaudron, L., Rossignol, J., and Dunbar, G.L. Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington’s Disease. Stem Cells Transl Med. 2014 May;3(5):620-31. doi: 10.5966/sctm.2013-0151. Epub 2014 Mar 21.PMID: 24657963

Fink, K.D., Rossignol, J., Crane, A.T., Davis, K.K., Bombard, M.C., Bavar, A.M., Clerc, S., Lowrance, S.A., Song, C., Lescaudron, L., and Dunbar, G.L. Transplantation of Umbilical-Cord-derived Mescenchymal Stem Cells into the R6/2 Mice: Behavioral and Neuropathological Analysis. Stem Cell Res Ther. 2013 Oct 24;4(5):130. doi: 10.1186/scrt341. PMID: 24456799

Rossignol J., Fink, K.D., K. Davis, S. Clerc, A. Crane, J. Matchynski, S. Lowrance, N. DeKorver, L. Lescaudron, G.L. Dunbar. Mesenchymal and adult neural stem cell transplantations in a transgenic rat model of Huntington’s disease. Stem Cells. 2014 Feb;32(2):500-9. doi: 10.1002/stem.1508. PMID:23939879

Lowrance, S.A., Fink, K.D., Crane, A., Matyas, J., Dey, N.D., Matchynski, J.J., Thibo, T., Reinke, T., Kippe, J., Hoffman, C., Sandstrom, M., Rossignol, J., and Dunbar, G.L. Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelien-1 rat model of stroke. Restor Neurol Neurosci. 2015;33(4):579-88. doi: 10.3233/RNN-130329. PMID: 23902985

Fink, K.D., Rossignol, J., Lu, M., Lévêque, X., Hulse, T.D., Crane, A.T., Nerriere-Daguin, V., Wyse, R.D., Starski, P.A., Schoop, M.T., Dues, D.J., Witte, S.J., Song, C., Vallier, L., Nguyen, T.H., Naveilhan, P., Anegon, I., Lescaudron, L, and Dunbar, G.L. Survival and differentiation of transplanted adenovirus-generated induced pluripotent stem cells Transplanted into the Rat Striatum. Cell Transplant. 2014;23(11):1407-23. doi: 10.3727/096368913X670958. Epub 2013 Jul 22. PMID: 23879897

Fink, K.D., Rossignol, J., Crane A.T., Davis, K.K., Bavar, A.M., Dekorver, N.W., Lowrance, S.A., Reilly, M.P., Sandstrom, M.I., von Hörsten, S., Lescaudron, L., Dunbar, G.L. Early Cognitive Dysfunction in the HD 51 CAG Transgenic Rat Model of Huntington’s disease. Behav Neurosci. 2012 Jun;126(3):479-87. doi: 10.1037/a0028028. PMID: 22642889

Lescaudron, L., Boyer, C., Bonnamain, V., Fink, K.D., Leveque, X., Rossignol, J., Nerriere-Daguin, V., Malouet, A.C., Lelan, F., Dey, N.D., Michel-Monigadon, D., Lu, M., Neveu, I., von Hörsten, S., Naveilhan, P., Dunbar, G.L. Assessing the potential clinical utility of transplantations of neural and mesenchymal stem cells for treating neurodegenerative diseases. Methods Mol Biol. 2012;879:147-64. doi: 10.1007/978-1-61779-815-3_10. PMID: 22610559

Crane, A.T.,* Fink, K.D.,* Smith, J.S. The effects of acute voluntary wheel running on recovery of function following medial frontal cortical contusions in rats. Restor Neurol Neurosci. 2012;30(4):325-33. doi: 10.3233/RNN-2012-120232. PMID: 22596352

Rossignol, J., Boyer, C., Lévêque, X., Fink, K.D.,Thinard, R., Blanchard, F., Dunbar, G.L., and Lescaudron, L. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: Morphological and behavioral outcomes Behav Brain Res. 2011 Mar 1;217(2):369-78. doi: 10.1016/j.bbr.2010.11.006. Epub 2010 Nov 9. PMID: 21070819