Positions
- Professor
-
Department of Neuroscience
Departments of Molecular and Cellular Biology, Neurology, and Neurosurgery
Baylor College of Medicine
Houston, TX
- Associate Director
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Graduate Program in Neuroscience
Baylor College of Medicine
- Faculty Member
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Graduate Programs in Neuroscience and Development, Disease Models, and Therapeutics (DDMT)
Baylor College of Medicine
- Vivan L. Smith Endowed Chair in Neuroscience
-
Baylor College Of Medicine
Addresses
- Department of Neuroscience (Lab)
-
Baylor College of Medicine
Houston, TX 77030
United States
Education
- BA from Amherst College
- 06/1991 - Amherst, Massachusetts United States
- Biology
- PhD from California Institute Of Technology
- 06/1999 - Pasadena, California United States
- Molecular and Cellular Neuroscience
- Advanced Training from Johns Hopkins University School Of Medicine
- 01/2003 - Baltimore, MD United States
Professional Statement
Our research focuses on the pathogenesis of Alzheimer’s disease. Broadly speaking, we want to understand factors that influence disease risk and dictate the stereotyped loss of neural circuits needed for memory. More specifically, we want to understand how aging increases the likelihood of dementia, how genetics may influence this risk, and how specific brain areas are selectively affected.Our laboratory uses transgenic mice as a model system that can be engineered to reproduce focused aspects of the disease. These models allow us to test cellular and molecular hypotheses about causes and consequences of disease pathology, and to define how interactions between genes, environment, and aging determine resilience or risk.
We are currently pursuing three avenues of study. One project explores the genetic basis of cognitive reserve by engineering mice to express a gene variant associated with preserved cognition in patients with Alzheimer's neuropathology. Complementary studies examine how brain aging contributes to Alzheimer's risk using mice designed to stop time through exogenous control of amyloid onset. Finally, we are investigating the basis for progressive neuronal vulnerability in Alzheimer's using mice created to test whether circuit function contributes to disease susceptibility. Our hope is that mice and men share sufficient similarities in genetic architecture, basic physiology, and neuronal circuitry to gain insight from one useful in understanding the other.
Key questions:
1. How do genetics influence whether individuals with amyloid pathology will progress to dementia or remain cognitively healthy?
2. How does aging contribute to AD? Why does this disease primarily strike late in life?
3. What makes neurons of the entorhinal cortex particularly vulnerable in AD? Might their normal role in episodic memory contribute to their frailty in disease?
Websites
Selected Publications
- Nguyen, Q. Wood, C.A., Kim, P.J, and Jankowsky, J.L. "The TMEM106B T186S coding variant increases neurite arborization and synaptic density in primary hippocampal neurons." Front. Neurosci.. 2023; Pubmed PMID: 37901434
- 50. Zhang, T., Pang, W., Feng, T., Guo, J., Wu, K., Nunez Santos, M., Arthanarisami, A., Nana, A.L., Nguyen, Q., Kim, P.J., Jankowsky, J.L., Seeley, W.L., Hu, F. "TMEM106B regulates microglial proliferation and survival in response to demyelination." Sci Adv. 2023; Pubmed PMID: 37146150
- 48. Koller, E.J., Comstock, M., Bean, J.C., Escobedo, G., Park, K.-W., Jankowsky, J.L. "Temporal and spatially-controlled APP transgene expression using Cre-dependent alleles." 2022; Pubmed PMID: 35394029
- 49. Zhao, R.*, Grunke, S.D.*, Wood, C.A.*, Perez, G.A., Comstock, M., Li, M.-H., Singh, A.K., Park, K.-W., Jankowsky, J.L. "Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction." eLife. 2022; Pubmed PMID: 36468693
- Park, K.-W., Wood, C.A., Li, J., Taylor, B.C., Oh, S.-W., Young, N.L, and Jankowsky, J.L. "Gene therapy using Abeta variants for amyloid reduction." Mol. Ther.. 2021; Pubmed PMID: 33647457
- Roy ER, Wang B, Wan YW, Chiu G, Cole A, Yin Z, Propson NE, Xu Y, Jankowsky JL, Liu Z, Lee VM, Trojanowski JQ, Ginsberg SD, Butovsky O, Zheng H, Cao W. "Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease." J. Clin. Invest.. 2020;130:1912-1930. Pubmed PMID: 31917687
- Huichalaf, C.H., Al-Ramahi, I.*, Park, K.W.*, Grunke, S.D., Lu, N., de Haro, M., El-Zein, K., Gallego-Flores, T., Perez, A.M., Jung, S.Y., Botas, J., Zoghbi, H.Y., and Jankowsky, J.L. "Cross-species genetic screens identify kinase targets for APP reduction in Alzheimer's disease." Hum. Mol. Genet.. 2019;28:2014-2029. Pubmed PMID: 30753434
- Lillehaug, S., Yetman, M.J., Puchades, M.A., Checinska, M.M, Kleven, H., Jankowsky, J.L., Bjaalie, J.G., and Leergaard, T.B. "Brain-wide distribution of reporter expression in five transgenic tetracycline-transactivator mouse lines." Sci. Data. 2019;6:190028. Pubmed PMID: 30806643
- Chiang, A.C-A., Fowler, S.W., Savjani, R.R., Hilsenbeck, S.G., Wallace, C.E., Cirrito, J.R., Das, P. and Jankowsky, J.L. "Combination anti-Aβ treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice." J. Exp. Med. 2018;215:1349-1364. Pubmed PMID: 29626114
- Chiang, A.C.A.*, Fowler, S.W.*, Reddy, R., Pletnikova, O., Troncoso, J.C., Sherman, M.A., Lesne, S., and Jankowsky, J.L. "Discrete pools of oligomeric amyloid-β track with spatial learning deficits in a mouse model of Alzheimer's amyloidosis." Am. J. Pathol.. 2017;
- Verbeeck, C.*, Carrano, A.*, Chakrabarty, P., Jankowsky, J.L., and Das, P. "Combination of Aβ suppression and innate immune activation in the brain significantly attenuates amyloid plaque deposition." Am. J. Pathol.. 2017; Pubmed PMID: 28919107
- Zheng, H. and Jankowsky, J.L. "Practical considerations for choosing a mouse model of Alzheimer's disease." Mol Neurodegener.. 2017;12(1):89. Pubmed PMID: 29273078
- Kim, J-Y., Jang, A., Reddy, R., Yoon, W.H., Jankowsky, J.L. "Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS." Hum. Mol. Genet.. 2016;25:4661-4673. Pubmed PMID: 28173107
- Zhao, R., Grunke, S.D., Keralapurath, M.M., Yetman, M.J., Lam, A., Lee, T.C., Jiang, Y., Swing, D.A., Tessarollo, L., Ji, D., and Jankowsky, J.L. "Impaired recall of positional memory following chemogenetic disruption of place field stability." Cell Repts.. 2016;16:1-12. Pubmed PMID: 27373150
- Lian, H. Litvinchuk, A., Chiang, A.C.-A., Aithmitti, N., Jankowsky, J.L., and Zheng, H. "Astrocyte-microglia crosstalk through complement activation modulates amyloid pathology in mouse models of Alzheimer's disease." J. Neurosci.. 2016;36:577-589. Pubmed PMID: 26758846
- Marin, M.A., Ziburkus, J., Jankowsky, J.L., and Rasband, M.N. "Amyloid-β plaques disrupt axon initial segments." Exp. Neurol.. 2016;281:93-98.
- Yetman, M.J., Fowler, S.W., and Jankowsky, J.L. "Humanized tau mice with regionalized amyloid exhibit behavioral deficits but no pathological interaction." PLoS ONE :. 2016;11:e0153724. Pubmed PMID: 27070146
- Kim, J.-Y.*, Grunke, S.D.*, and Jankowsky, J.L. "Widespread neuronal transduction of the rodent CNS via intraventricular viral injection of the neonate." Method. Mol. Biol.. 2016; Pubmed PMID: 26611591
- Liu P, Reed MN, Kotilinek LA, Grant MK, Forster CL, Qiang W, Shapiro SL, Reichl JH, Chiang AC, Jankowsky JL, Wilmot CM, Cleary JP, Zahs KR, Ashe KH "Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration." Cell Repts. 2015; Pubmed PMID: 26051935
- Lian H, Yang L, Cole A, Sun L, Chiang AC, Fowler SW, Shim DJ, Rodriguez-Rivera J, Taglialatela G, Jankowsky JL, Lu HC, Zheng H "NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease." Neuron. 2015;85(1):101-15. Pubmed PMID: 25533482
- Wang J, Wegener JE, Huang TW, Sripathy S, et al. "Wild-type microglia do not reverse pathology in mouse models of Rett syndrome." Nature. 2015;521(7552):E1-4. Pubmed PMID: 25993969
- Yetman MJ, Lillehaug S, Bjaalie JG, Leergaard TB, Jankowsky JL "Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex." Brain Struct. Funct.. 2015; Pubmed PMID: 25869275
- Kim, J.-Y.*, Grunke, S.D.*, Levites, Y., Golde, T.E., and Jankowsky, J.L. "Intracerebroventricular viral injection for widespread transduction of the neonatal mouse brain." J. Vis. Exp..;
- Fowler, S.W.*, Chiang, A. C-A.*, Savjani, R.R., Larson, M.E., Schuler, D.R., Cirrito, J.R., Lesne, S., and Jankowsky, J.L. "Genetic modulation of soluble Aβ rescues cognitive and synaptic impairment in a mouse model of Alzheimer’s disease." J. Neurosci.. 2014;34:7871-7885. Pubmed PMID: 24899710
- Zhao R, Fowler SW, Chiang AC, Ji D, Jankowsky JL "Impaired refinement of hippocampal place cells during maze habituation limits spatial learning in a mouse model of Alzheimer’s disease." Hippocampus. 2014;24:963-78. Pubmed PMID: 24752989
- Born HA, Kim JY, Das P, Dabaghian Y, Guo Q, Yoo JW, Schuler DR, Cirrito JR, Zheng H, Golde TE, Noebels JL, Jankowsky JL "Genetic suppression of transgenic APP rescues hypersynchronous network activity in a mouse model of Alzheimer’s disease." J. Neurosci. 2014;34:3826-40. Pubmed PMID: 24623762
- Sun MY, Yetman MJ, Lee TC, Chen Y, Jankowsky JL "Specificity and efficiency of reporter expression in adult neural progenitors vary substantially among nestin-CreERT2 lines." J. Comp. Neurol. 2014;522:1191-1208. Pubmed PMID: 24519019
- Tanifum, E.A., Starosolski, Z.A., Ghaghada, K., Fowler, S.W., Jankowsky, J.L. "Computed tomography for detection of vascular leak in a mouse model of amyloid neuropathology." J. Cereb. Blood Flow Metab..;
- Kim JY, Ash RT, Ceballos-Diaz C, Levites Y, Golde TE, Smirnakis SM, Jankowsky JL "Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo.." Eur. J. Neurosci.. 2013 Apr;37(8):1203-20. Pubmed PMID: 23347239
- Yetman MJ, Jankowsky JL "Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment." J. Neurosci. 2013;33:17335-41. Pubmed PMID: 24174666
- Chakrabarty, P., Rosario, A., Cruz, P., Siemienski, Z., Ceballos-Diaz, C., Crosby, K., Jansen, K., Borchelt, D.R., Kim, J.-Y., Jankowsky, J.L., Golde, T.E., and Levites, Y. "Capsid serotype and timing of injection determines AAV transduction in the neonatal mouse brain." PLoS ONE. 2013;8:e67680. Pubmed PMID: 23825679
- Rodgers SP, Born HA, Das P, Jankowsky JL "Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult.." Mol Neurodegener. 2012;7:28. Pubmed PMID: 22709352
- Han HJ, Allen CC, Buchovecky CM, Yetman MJ, Born HA, Marin MA, Rodgers SP, Song BJ, Lu HC, Justice MJ, Probst FJ, Jankowsky JL "Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator.." J. Neurosci.. 2012 Aug 1;32(31):10574-86. Pubmed PMID: 22855807
- Cowin RM, Roscic A, Bui N, Graham D, Paganetti P, Jankowsky JL, Weiss A, Paylor R "Neuronal aggregates are associated with phenotypic onset in the R6/2 Huntington's disease transgenic mouse.." Behav. Brain Res.. 2012 Apr 15;229(2):308-19. Pubmed PMID: 22306231
- Wang A, Das P, Switzer RC, Golde TE, Jankowsky JL "Robust amyloid clearance in a mouse model of Alzheimer's disease provides novel insights into the mechanism of amyloid-beta immunotherapy.." J. Neurosci.. 2011 Mar 16;31(11):4124-36. Pubmed PMID: 21411653
- Badea A, Johnson GA, Jankowsky JL "Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease.." Neuroimage. 2010 Apr 1;50(2):416-27. Pubmed PMID: 20035883
- Moss FJ, Imoukhuede PI, Scott K, Hu J, Jankowsky JL, Quick MW, Lester HA "GABA transporter function, oligomerization state, and anchoring: correlates with subcellularly resolved FRET.." J. Gen. Physiol.. 2009 Dec;134(6):489-521. Pubmed PMID: 19948998
- Verret L, Jankowsky JL, Xu GM, Borchelt DR, Rampon C "Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis.." J. Neurosci.. 2007 Jun 20;27(25):6771-80. Pubmed PMID: 17581964
- Jankowsky JL, Younkin LH, Gonzales V, Fadale DJ, Slunt HH, Lester HA, Younkin SG, Borchelt DR "Rodent Aβ modulates the solubility and distribution of amyloid deposits in transgenic mice.." J. Biol. Chem.. 2007 Aug 3;282(31):22707-20. Pubmed PMID: 17556372
- Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV "Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease.." J. Neurosci.. 2005 May 25;25(21):5217-24. Pubmed PMID: 15917461
- Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR "Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease.." PLoS Med.. 2005 Dec;2(12):e355. Pubmed PMID: 16279840
- Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR "Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.." Hum. Mol. Genet.. 2004 Jan 15;13(2):159-70. Pubmed PMID: 14645205
- Jankowsky JL, Slunt HH, Gonzales V, Jenkins NA, Copeland NG, Borchelt DR "APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1.." Neurobiol. Aging. 2004 Aug;25(7):885-92. Pubmed PMID: 15212842
- Jankowsky JL, Xu G, Fromholt D, Gonzales V, Borchelt DR "Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease.." J. Neuropathol. Exp. Neurol.. 2003 Dec;62(12):1220-7. Pubmed PMID: 14692698
- Jankowsky JL, Savonenko A, Schilling G, Wang J, Xu G, Borchelt DR "Transgenic mouse models of neurodegenerative disease: opportunities for therapeutic development.." Curr Neurol Neurosci Rep. 2002 Sep;2(5):457-64. Pubmed PMID: 12169227
- Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR "Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.." Biomol. Eng.. 2001 Jun;17(6):157-65. Pubmed PMID: 11337275
- Lesuisse C, Xu G, Anderson J, Wong M, Jankowsky J, Holtz G, Gonzalez V, Wong PC, Price DL, Tang F, Wagner S, Borchelt DR "Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.." Hum. Mol. Genet.. 2001 Oct 15;10(22):2525-37. Pubmed PMID: 11709540
- Jankowsky JL, Patterson PH "The role of cytokines and growth factors in seizures and their sequelae.." Prog. Neurobiol.. 2001 Feb;63(2):125-49. Pubmed PMID: 11124444
- Jankowsky JL, Patterson PH "Cytokine and growth factor involvement in long-term potentiation.." Mol. Cell. Neurosci..;14(41369):273-86. Pubmed PMID: 10588384
- Jankowsky JL, Derrick BE, Patterson PH "Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques.." Learn. Mem..;7(6):400-12. Pubmed PMID: 11112799
- Jankowsky JL, Patterson PH "Differential regulation of cytokine expression following pilocarpine-induced seizure.." Exp. Neurol.. 1999 Oct;159(2):333-46. Pubmed PMID: 10506506
- Edwards GA 3rd, Wood CA, He Y, Nguyen Q, Kim PJ, Gomez-Gutierrez R, Park KW, Xu Y, Zurhellen C, Al-Ramahi I, Jankowsky JL "TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy." Acta Neuropathol. 2024; Pubmed PMID: 38526616
- Koller EJ, Wood CA, Lai Z, Borgenheimer E, Hoffman KL, Jankowsky JL. "Doxycycline for transgene control disrupts gut microbiome diversity without compromising acute neuroinflammatory response." J Neuroinflammation. 2024; Pubmed PMID: 38178148
- Perez GA, Park KW, Lanza D, Cicardo J, Uddin MD, Jankowsky JL. "Generation of a Dcx-CreERT2 knock-in mouse for genetic manipulation of newborn neurons." Genesis. 2023; Pubmed PMID: 38102875
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