Contact

Department

Cellular and Integrative Physiology and the Barshop Insitute for Longevity and Aging Studies

Candice Van Skike

Postdoctoral Fellow

Personal Statement:

Lab Affiliation:
Veronica Galvan, Ph.D.


Research

The goal of Dr. Van Skike’s research is to identify the mechanisms that contribute to cerebrovascular dysfunction in Alzheimer’s disease and aging. Recent work in both humans and animal models have demonstrated that deficits in cerebral blood flow (CBF) emerge prior to the onset of cognitive dysfunction, suggesting that altered CBF may present an opportunity for early detection and intervention in a disease that currently has no cure. The research in the Galvan lab has identified that the mTOR pathway contributes to brain vascular dysfunction and cognitive decline in Alzheimer’s disease and aging; therefore inhibitors of the mTOR pathway may have potential as a therapeutic intervention.

Dr. Van Skike specializes in the use of in vivo techniques, including intravital two-photon microscopy and laser Doppler flowmetry, to measure CBF, vasodilatory capacity, and blood-brain barrier integrity in mouse models of AD. Additionally, her research utilizes immunofluorescent confocal microscopy and cell culture to identify the mTOR-dependent mechanisms involved in CBF dysfunction. She is also highly trained in rodent behavioral testing, including spatial learning and memory tasks, hippocampal dependent contextual memory, recognition memory, anxiety, and assays of motor function.

Awards & Accomplishments

2018                APSselect award from the American Physiological Society

2017                Joe H. Ward Jr. and Bettie B. Ward Award for Excellence in the Study of the Biology of Aging: Postdoctoral Fellow

2017                1st Place Poster Presentation Award at the Barshop Symposium on Aging

2017                Deposition of tau oligomers in cerebrovasculature of human Alzhiemer’s disease brains featured on the cover of Aging and Disease, Volume 8, Issue 3.

2016                F1000 Outstanding Presentation Prize at the New York Academy of Sciences Symposium on “Alzheimer’s Disease as a Neurovascular Inflammatory Disorder”

2016                Travel Award to attend the New York Academy of Sciences Symposium on “Alzheimer’s Disease as a Neurovascular Inflammatory Disorder”

2016                In vivo two photon microscopy of neurovascular amyloidosis and blood-brain barrier breakdown in a living 18 month old Tg2576 mouse modeling Alzheimer’s disease featured on the cover of AGE, Volume 38, Issues 4-5.

2016                American Aging Association Travel Award

2014 – 2015    Research Society on Alcoholism Junior Investigator Award

2009 – 2013    Research Society on Alcoholism Student Merit Award

2012 – 2013    Baylor Graduate School Travel Award

Affiliations

Research Support:
Ongoing Research Support
AARF-17-504221
Van Skike (PI)
Alzheimer’s Association 08/01/17-07/31/19
Oligomeric tau-induced microvascular dysfunction in Alzheimer’s disease
The major goal of this project is to determine the mechanism by which the TOR pathway drives tau-mediated cerebromicrovascular dysfunction using both in vitro and in vivo techniques. This will provide crucial information on TOR’s mechanisms of action on tau-induced cerebrovascular dysfunction in Alzheimer’s disease, which is the most common tauopathy.
Role: PI

Completed Research Support
T32 AG021890
Musi (PI)
NIH/National Institute on Aging 10/01/15-07/31/17
Training Grant on the Biology of Aging
The goal of my training project was to elucidate the role of mTOR in conferring neuronal deficits in Alzheimer’s disease through the regulation of cerebral blood flow and blood-brain barrier integrity.
Role: Postdoctoral Fellow

T32 DA016176
Dwoskin (PI)
NIH/National Institute on Drug Abuse 06/01/14-09/31/15
Training in Drug Abuse Related Research
The goal of my training project was to identify and test novel natural compounds as a cessation agent for nicotine and alcohol polysubstance use.
Role: Postdoctoral Fellow

 

Publications

Publications (as of March 2018):
Hussong SA, Van Skike CE, Olson AB, Hart MJ, Dineley K, Ungvari Z, Perez V, Kayed R, Galvan V (In Review). Transcellular propagation of tau aggregates in brain microvascular endothelial cells promotes cellular senescence and blocks eNOS activation: Potential role in neurovascular dysfunction in tau transgenic mice. Currently under review.

Van Skike CE, Jahrling JB, Olson A, Sayre N, Hussong SA, Ungvari Z, Lechleiter J, Galvan V (Epub). Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer’s disease and vascular cognitive impairment. American Journal of Physiology – Heart and Circulatory Physiology. *APSselect awarded by the American Physiological Society

Van Skike CE, Galvan V (Epub). A perfect sTORm: The role of the mammalian target of rapamycin (mTOR) in cerebrovascular dysfunction of Alzheimer’s disease – A Mini-Review. Gerontology. PMID: 29320772

Zhang S-Y, Clark NE, Freije CA, Pauwels E, Taggart A, Okada S, Mandel H, Garcia P, Ciancanelli MJ, Biran A, Lafaille FG, Tsumura M, Cobat A, Luo J, Volpi S, Zimmer B, Sakata S, Dinis A, Ohara O, Garcia Reino EJ, Dobbs K, Hasek M, Holloway SP, McCammon K, Hussong SA, DeRosa N, Lorenzo L, Hyodo M, Van Skike CE, Katolik A, Faria E, Halwani R, Fukuhara R, Galvan V, Damha MJ, Al-Muhsen S, Itan Y, Boeke JD, Notarangelo LD, Studer L, Kobayashi M, Diogo L, Fairbrother W, Abel L, Rosenberg B, Hart J, Etzioni A, Casanova J-L (2018). Inborn errors of lariat metabolism in humans with viral infections of the brainstem. Cell, 172 (5), 952-965. PMID: 29474921

Jahrling JB, Lin A, DeRosa N, Hussong S, Van Skike CE, Girotti M, Javors M, Zhao Q, Maslin LA, Asmis R, Galvan V (2018). mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment. Journal of Cerebral Blood Flow and Metabolism, 38 (1), 58-74. PMID: 28511572 PMCID: PMC5757441

Castillo-Carranza DL, Nilson AN, Van Skike CE, Jahrling JB, Patel K, Garach P, Gerson JE, Sengupta U, Abisambra J, Nelson P, Troncoso J, Ungvari Z, Galvan V, Kayed R (2017). Cerebral microvascular accumulation of tau oligomers in Alzheimer’s disease and related tauopathies. Aging and Disease, 8 (3), 257-266. PMID: 28580182 PMCID: PMC5440106 *Featured on the journal cover 

Matthews DB, Novier A, Diaz-Granados JL, Van Skike CE, Ornelas L, Mittleman G (2017). Impact of adolescent alcohol use across the lifespan: long-lasting tolerance to high dose alcohol coupled with potentiated spatial memory impairments to moderate dose alcohol. Alcohol, 61, 33-42PMID: 28479015 

Van Skike CE, Casey EM, Maggio SE, Reynolds AR, Bardo MT, Dwoskin LP, Prendergast MA, & Nixon K (2016). Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse. Progress in Neuro-psychopharmacology and Biological Psychiatry, 65, 269-287. PMID: 26582145 PMCID: PMC4679525

Van Skike CE, Diaz-Granados JL, & Matthews DB (2015). Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats. Alcoholism: Clinical and Experimental Research, 39 (2), 262-271. PMID: 25684048 PMCID: PMC4331453

Ornelas LC, Novier A, Van Skike CE, Diaz-Granados JL, & Matthews DB (2015). The effects of acute ethanol on motor impairments in adolescent, adult, and aged rats. Alcohol, 49 (2), 121-126. PMID: 25613215

Squeglia LM, Boissoneault J, Van Skike CE, Nixon SJ, & Matthews DB (2014). Differential effects of alcohol across the lifespan: Recent insights from adolescent, adult, and aged populations using human and animal models. Alcoholism: Clinical and Experimental Research, 38 (10), 2509-2516. PMID: 25156779 PMCID: PMC4211934

Novier A, Van Skike CE, Diaz-Granados JL, Mittleman G, & Matthews DB (2013). Acute alcohol produces ataxia and cognitive impairments in aged animals: a comparison between young adult and aged rats. Alcoholism: Clinical and Experimental Research. PMID: 23550918

Novier A, Van Skike CE, Chin VS, Diaz-Granados JL, & Matthews DB (2012) Low and moderate doses of acute ethanol do not impair spatial cognition but facilitate accelerating rotarod performance in adolescent and adult rats. Neuroscience Letters, 512, 38-42. PMID: 23550918

Van Skike CE, Novier A, Diaz-Granados JL, & Matthews DB (2012). The effect of chronic intermittent ethanol exposure on spatial memory in adolescent rats: the dissociation of metabolic and cognitive tolerances.  Brain Research, 1453, 34-39. PMID: 22464184

Chin VS, Van Skike CE, Berry RB, Kirk RE, Diaz-Granados JL, & Matthews DB (2011). Effects of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats. Alcohol, 45 (5), 473-483. PMID: 21600728

Chin VS*, Van Skike CE*, & Matthews DB (2010). Effects of ethanol on hippocampal function during adolescence: a look at the past and thoughts on the future. Alcohol, 44, 3-14. PMID: 20113870 *Denotes equal contribution.

Van Skike CE, Botta P, Chin VS, Tokunaga S, Silvers JM, Venard J, Diaz-Granados JL, Valenzuela CF, & Matthews DB (2010). Behavioral Effects of Ethanol in Cerebellum are Age Dependent: Potential System and Molecular Mechanisms. Alcoholism: Clinical and Experimental Research, 34(12), 2070-2080. PMID: 20860615 PMCID: PMC2988915

Selected Presentations:
Before the onset: Cerebrovascular mechanisms of Alzheimer’s disease. Oral presentation at the Barshop Institute Seminar Series, November 2017, UT Health SA. *Received the Joe and Bettie Ward Award for Excellence in the Study of the Biology of Aging

Cerebrovascular dysfunction in Alzheimer’s disease. Oral presenation at the Edward J. Masoro Biology of Aging Student Day, April 2017, UT Heath SA.

Neurobiology of substance abuse during adolescence. Invited speaker at the 7th Annual Voelcker Biosciences Teacher Academy, February 2017, UT Heath SA.

TOR drives cerebrovascular dysfunction in Alzheimer’s disease. Oral presentation at the Barshop Institute Seminar Series, December 2016, UT Health SA.

mTOR dependent cerebrovascular dysfunction in Alzheimer’s disease: a two-photon imaging study. Oral presentation at the Tea and Biscuits Neuroscience Club, August 2016, UT Health SA.

Behavioral, electrophysiological, and molecular differences between adolescent and adult rats in response to ethanol. Symposium presented at the National Research Society on Alcoholism Conference, June 2013. Orlando, FL.

Selected Posters:
Van Skike CE, Hussong SA, Jahrling JB, DeRosa N, Hernandez SF, Reyna ME, Galvan V (2017, October). mTOR-dependent neuronal nitric oxide dysfunction underlies neurovascular coupling deficits in a model of Alzheimer’s disease. Poster session presented at the Barshop Symposium on Aging, Bandera, TX. *Received 1st Place Poster Presentation Award

Van Skike CE, Hussong SA, Jahrling JB, DeRosa N, Hernandez SF, Reyna ME, Galvan V (2017, September). mTOR-dependent neuronal nitric oxide dysfunction underlies neurovascular coupling deficits in a model of Alzheimer’s disease. Poster session presented at the San Antonio Postdoctoral Research Forum, San Antonio, TX.

Van Skike CE, Jahrling JB, Hernandez SF, DeRosa N, Galvan V (2017, April). TOR drives fibrillar amyloid-β accumulation and cerebrovascular dysfunction in mouse models of Alzheimer’s disease. Poster session presented at the International Society for Cerebral Blood Flow and Metabolism’s Brain and Brain PET 2017 Conference, Berlin, Germany.

Van Skike CE, Jahrling JB, Hernandez SF, DeRosa N, Galvan V (2016, December). TOR drives fibrillar amyloid-β accumulation and cerebrovascular dysfunction in the Tg2576 model of Alzheimer’s disease. Poster session presented at the New York Academy of Science Conference entitled Alzheimer’s Disease as a Neurovascular Inflammatory Disorder, New York, NY. *Received F1000 Outstanding Presentation Award

Van Skike CE, Jahrling JB, DeRosa N, Galvan V (2016, October). TOR drives cerebral amyloid angiopathy in a mouse model of Alzheimer’s disease. Poster session presented at the Barshop Symposium on Aging, Bandera, TX.

Van Skike CE, Lin A-L, Burbank R, Halloran J, Cuvillier J, Hussong SA, Jahrling JB, Austad S, Fischer K, Galvan V (2016, June). A Key Role of TOR in cognitive and brain vascular aging. Poster session presented at the American Aging Association, Seattle, WA.