Roland Shytle, PhD

Associate Professor, Center of Excellence for Aging & Brain Repair

Assoc Professor, College of Medicine Psychiatry and Behavioral Neurosciences

Contact Info

• CEABR, MDC-78, USF Health
  12901 Bruce B. Downs Blvd.
  Tampa FL 33612
• Academic Email: dshytle@usf.edu
• Academic Phone: (813) 974-9171
• View My C.V.

Education

Academic Philosophy

Interdisciplinary and Emerging Signature Programs

• Neurodegenerative Disease
• Neuroscience

Research Interests

• During my scientific career, I have focused on primarily translational research in neuropsychiatry and neurodevelopmental disorders. The first involved investigating the therapeutic potential of acetylcholinergic nicotinic receptor inhibition for treating neuropsychiatric disorders, such as Tourette's syndrome. This research began with investigating the off label clinical use of transdermal nicotine and mecamylamine for Tourette's, which led to R&D of S-(+)-mecamylamine (TC-5214; Amplexa) for mood disorders. My translational research in this area led to the development and validation of 3 psychometric scales and 1 structured diagnostic interview based on DSM-IV for neuropsychiatric disorders. In recent years, my focus shifted to drug discovery for neurodegenerative disorders by optimizing the bioavailability of natural therapeutic agents, such as bioflavonoids and novel lithium salts employing nanolipidic encapsulation and cocrystal formulation development.

Recent Publications

• Leon M, Sawmiller D, Shytle RD, Tan J. Therapeutic Cocktail Approach for Treatment of Hyperhomocysteinemia in Alzheimer''s Disease. Cell medicine. 10: 2155179017722280, 2018.
• Habib A, Sawmiller D Li S Xiang Y Rongo D Tian J Hou H Zeng J Smith A Fan S Giunta B Mori T Currier G Shytle RD and Tan J. LISPRO mitigates β-amyloid and associated pathologies in Alzheimer’s mice Cell Death and Disease 8. 8: e; doi:10.1038/cddis.2017.279, 2017.
• Habib A, Sawmiller D, Li S, Xiang Y, Rongo D, Tian J, Hou H, Zeng J, Smith A, Fan S, Giunta B, Mori T, Currier G, Shytle DR, Tan J. LISPRO mitigates β-amyloid and associated pathologies in Alzheimer''s mice. Cell death & disease. 8(6) : e2880, 2017.
• Sawmiller D, Li S, Mori T, Habib A, Rongo D, Delic V, Bradshaw PC, Shytle RD, Sanberg C, Bickford P, Tan J. Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer''s disease. Heliyon. 3(4) : e00279, 2017.
• Grimmig B Kim S-H Nash K Bickford PC Shytle RD. Neuroprotective mechanisms of astaxanthin: a potential therapeutic role in preserving cognitive function in age and neurodegeneration. GeroScience.. 39(1) : 19-32. doi:10.1007/s11357-017-9958-x., 2017.
• Sawmiller D, Habib A, Li S, Darlington D, Hou H, Tian J, Shytle RD, Smith A, Giunta B, Mori T, Tan J. Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice. Journal of neuroimmunology. 299: 98-106, 2016.
• Garbuzova-Davis S, Thomson A, Kurien C, Shytle RD, Sanberg PR. Potential new complication in drug therapy development for amyotrophic lateral sclerosis. Expert review of neurotherapeutics. 16(12) : 1397-1405, 2016.
• Kim SH, Smith AJ, Tan J, Shytle RD, Giunta B. MSM ameliorates HIV-1 Tat induced neuronal oxidative stress via rebalance of the glutathione cycle. American journal of translational research. 7(2) : 328-38, 2015.
• Osborn KE, Shytle RD, Frontera AT, Soble JR, Schoenberg MR. Addressing potential role of magnesium dyshomeostasis to improve treatment efficacy for epilepsy: A reexamination of the literature. Journal of clinical pharmacology. , 2015.
• Ehrhart J, Smith AJ, Kuzmin-Nichols N, Zesiewicz TA, Jahan I, Shytle RD, Kim SH, Sanberg CD, Vu TH, Gooch CL, Sanberg PR, Garbuzova-Davis S. Humoral factors in ALS patients during disease progression. Journal of neuroinflammation. 12: 127, 2015.
• Bickford PC, Kaneko Y, Grimmig B, Pappas C, Small B, Sanberg CD, Sanberg PR, Tan J, Douglas Shytle R. Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells. Age (Dordrecht, Netherlands). 37(5) : 103, 2015.
• Smith AJ, Kim SH, Tan J, Sneed KB, Sanberg PR, Borlongan CV, Shytle RD. Plasma and Brain Pharmacokinetics of Previously Unexplored Lithium Salts. RSC advances. 4(24) : 12362-12365, 2014.
• Small BJ, Rawson KS, Martin C, Eisel SL, Sanberg CD, McEvoy CL, Sanberg PR, Shytle RD, Tan J, Bickford PC. Nutraceutical intervention improves older adults'' cognitive functioning. Rejuvenation research. 17(1) : 27-32, 2014.
• Zhang SQ, Sawmiller D, Li S, Rezai-Zadeh K, Hou H, Zhou S, Shytle D, Giunta B, Fernandez F, Mori T, Tan J. Octyl gallate markedly promotes anti-amyloidogenic processing of APP through estrogen receptor-mediated ADAM10 activation. PloS one. 8(8) : e71913, 2013.
• Bailey AR, Hou H, Song M, Obregon DF, Portis S, Barger S, Shytle D, Stock S, Mori T, Sanberg PG, Murphy T, Tan J. GFAP expression and social deficits in transgenic mice overexpressing human sAPPα. Glia. 61(9) : 1556-69, 2013.
• Smith AJ, Kavuru P, Arora KK, Kesani S, Tan J, Zaworotko MJ, Shytle RD. Crystal engineering of green tea epigallocatechin-3-gallate (EGCg) cocrystals and pharmacokinetic modulation in rats. Molecular pharmaceutics. 10(8) : 2948-61, 2013.
• Smith AJ, Kim SH, Duggirala NK, Jin J, Wojtas L, Ehrhart J, Giunta B, Tan J, Zaworotko MJ, Shytle RD. Improving lithium therapeutics by crystal engineering of novel ionic cocrystals. Molecular pharmaceutics. 10(12) : 4728-38, 2013.
• Shytle RD, Tan J, Bickford PC, Rezai-Zadeh K, Hou L, Zeng J, Sanberg PR, Sanberg CD, Alberte RS, Fink RC, Roschek B. Optimized turmeric extract reduces β-Amyloid and phosphorylated Tau protein burden in Alzheimer''s transgenic mice. Current Alzheimer research. 9(4) : 500-6, 2012.
• Sanberg PR, Vindrola-Padros C, Shytle RD. Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette''s, depression, and beyond. Physiology & behavior. 107(5) : 801-8, 2012.
• Smith AJ, Kavuru P, Wojtas L, Zaworotko MJ, Shytle RD. Cocrystals of quercetin with improved solubility and oral bioavailability. Molecular pharmaceutics. 8(5) : 1867-76, 2011.
• Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, Tan J, Cao C, Shytle RD, Bradshaw PC. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer''s amyloid-induced mitochondrial dysfunction. Journal of Alzheimer''s disease : JAD. 26(3) : 507-21, 2011.
• Giunta B, Ehrhart J, Obregon DF, Lam L, Le L, Jin J, Fernandez F, Tan J, Shytle RD. Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders. Molecular brain. 4(1) : 23, 2011.
• Smith AJ, Giunta B, Shytle RD, Blum JM. Evaluation of a novel supplement to reduce blood glucose through the use of a modified oral glucose tolerance test. American journal of translational research. 3(2) : 219-25, 2011.
• Storch EA, De Nadai AS, Lewin AB, McGuire JF, Jones AM, Mutch PJ, Shytle RD, Murphy TK. Defining treatment response in pediatric tic disorders: a signal detection analysis of the Yale Global Tic Severity Scale. Journal of child and adolescent psychopharmacology. 21(6) : 621-7, 2011.
• Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation. PloS one. 5(5) : e10496, 2010.
• Shytle DR, Tan J, Ehrhart J, Smith AJ, Sanberg CD, Sanberg PR, Anderson J, Bickford PC. Effects of blue-green algae extracts on the proliferation of human adult stem cells in vitro: a preliminary study. Medical science monitor : international medical journal of experimental and clinical research. 16(1) : BR1-5, 2010.
• Smith A, Giunta B, Bickford PC, Fountain M, Tan J, Shytle RD. Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer''s disease. International journal of pharmaceutics. 389(1-2) : 207-12, 2010.
• Giunta B, Hou H, Zhu Y, Salemi J, Ruscin A, Shytle RD, Tan J. Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice. Neuroscience letters. 471(3) : 134-8, 2010.
• Sheehan DV, Sheehan KH, Shytle RD, Janavs J, Bannon Y, Rogers JE, Milo KM, Stock SL, Wilkinson B. Reliability and validity of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). The Journal of clinical psychiatry. 71(3) : 313-26, 2010.
• Bacher I, Wu B, Shytle DR, George TP. Mecamylamine - a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Expert opinion on pharmacotherapy. 10(16) : 2709-21, 2009.
• Parker-Athill E, Luo D, Bailey A, Giunta B, Tian J, Shytle RD, Murphy T, Legradi G, Tan J. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. Journal of neuroimmunology. 217(1-2) : 20-7, 2009.
• Shytle RD, Bickford PC, Rezai-zadeh K, Hou L, Zeng J, Tan J, Sanberg PR, Sanberg CD, Roschek B, Fink RC, Alberte RS. Optimized turmeric extracts have potent anti-amyloidogenic effects. Current Alzheimer research. 6(6) : 564-71, 2009.
• Alexander J, Keles G, Killingsworth J, Bronson R, Perez C, Sawmiller D, Shytle RD. Autism, heparan sulfate and potential interventions. Experimental neurology. 353: 114050, 2022.
• Rezai-Zadeh K, Douglas Shytle R, Bai Y, Tian J, Hou H, Mori T, Zeng J, Obregon D, Town T, Tan J. Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer''s disease beta-amyloid production. Journal of cellular and molecular medicine. 13(3) : 574-88, 2009.
• Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, Shytle RD, Tan J. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain research. 1214: 177-87, 2008.
• Park YJ, Farooq J, Cho J, Sadanandan N, Cozene B, Gonzales-Portillo B, Saft M, Borlongan MC, Borlongan MC, Shytle RD, Willing AE, Garbuzova-Davis S, Sanberg PR, Borlongan CV. Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics. Stem cell reviews and reports. 17(1) : 9-32, 2021.
• George TP, Sacco KA, Vessicchio JC, Weinberger AH, Shytle RD. Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. Journal of clinical psychopharmacology. 28(3) : 340-4, 2008.
• Habib A, Sawmiller D, Li S, Xiang Y, Rongo D, Tian J, Hou H, Zeng J, Smith A, Fan S, Giunta B, Mori T, Currier G, Shytle DR, Tan J. Retraction Note to: LISPRO mitigates β-amyloid and associated pathologies in Alzheimer''s mice. Cell death & disease. 12(12) : 1142, 2021.
• Rezai-Zadeh K, Ehrhart J, Bai Y, Sanberg PR, Bickford P, Tan J, Shytle RD. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. Journal of neuroinflammation. 5: 41, 2008.
• Killingsworth J, Sawmiller D, Shytle RD. Propionate and Alzheimer''s Disease. Frontiers in aging neuroscience. 12: 580001, 2020.
• Habib A, Shytle RD, Sawmiller D, Koilraj S, Munna SA, Rongo D, Hou H, Borlongan CV, Currier G, Tan J. Comparing the effect of the novel ionic cocrystal of lithium salicylate proline (LISPRO) with lithium carbonate and lithium salicylate on memory and behavior in female APPswe/PS1dE9 Alzheimer''s mice. Journal of neuroscience research. 97(9) : 1066-1080, 2019.
• Shytle RD, Eve DJ, Kim SH, Spiegel A, Sanberg PR, Borlongan CV. Retrospective Case Series of Traumatic Brain Injury and Post-Traumatic Stress Disorder Treated with Hyperbaric Oxygen Therapy. Cell transplantation. 28(7) : 885-892, 2019.