Darrell Sawmiller, PhD

Assistant Professor, Center of Excellence for Aging & Brain Repair

Contact Info

• Academic Email: dsawmill@usf.edu
• Academic Phone: (813) 974-6169

Education

Interdisciplinary and Emerging Signature Programs

• Cardiovascular Sciences
• Cellular and Molecular Biology
• Neurodegenerative Disease
• Neuroscience

Research Interests

• I have a broad background in animal, whole organ, molecular signaling and neuroscience. Since 2012, I have been investigating the therapeutic potential of natural compounds, including octyl gallate, diosmin, PQQ and LISPRO, a cocrystal of lithium salicylate and proline, for the treatment of Alzheimer's disease-like pathology in cell culture and animal models. Recently, we have synthesized lithium cholesterol sulfate, which we hypothesize will have improved bioavailability to the brain for AD treatment. These studies are important and timely since there is currently no effective treatment which slows the progression of AD. In addition, I have been utilizing this background to investigate the pathogenesis of autism, particularly the role of heparan sulfate deficiency in the neurogenic niches of the brain, as well as potential interventions for this disorder.

Recent Publications

• 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.
• Killingsworth J, Sawmiller D, Shytle RD. Propionate and Alzheimer''s Disease. Frontiers in aging neuroscience. 12: 580001, 2020.
• Mori T, Koyama N, Yokoo T, Segawa T, Maeda M, Sawmiller D, Tan J, Town T. Gallic acid is a dual α/β-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer mice. The Journal of biological chemistry. 295(48) : 16251-16266, 2020.
• Sawmiller D, Habib A, Hou H, Mori T, Fan A, Tian J, Zeng J, Giunta B, Sanberg PR, Mattson MP, Tan J. A Novel Apolipoprotein E Antagonist Functionally Blocks Apolipoprotein E Interaction With N-terminal Amyloid Precursor Protein, Reduces β-Amyloid-Associated Pathology, and Improves Cognition. Biological psychiatry. 86(3) : 208-220, 2019.
• 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.
• Wen F, Wu ZY, Nie L, Zhang QZ, Qin YK, Zhou ZL, Wu JJ, Zhao X, Tan J, Sawmiller D, Zi D. Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells. Bioscience reports. 39(8) , 2019.
• Yang C, Fan F, Sawmiller D, Tan J, Wang Q, Xiang Y. C1q/TNF-related protein 9: A novel therapeutic target in ischemic stroke? Journal of neuroscience research. 97(2) : 128-136, 2019.
• Wen J, Sawmiller D, Wheeldon B, Tan J. A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity. CNS & neurological disorders drug targets. 18(10) : 769-778, 2019.
• Wang L, Hou H, Zi D, Habib A, Tan J, Sawmiller D. Novel apoE receptor mimetics reduce LPS-induced microglial inflammation. American journal of translational research. 11(8) : 5076-5085, 2019.
• Habib A, Hou H, Mori T, Tian J, Zeng J, Fan S, Giunta B, Sanberg PR, Sawmiller D, Tan J. Human Umbilical Cord Blood Serum-derived α-Secretase: Functional Testing in Alzheimer''s Disease Mouse Models. Cell transplantation. 27(3) : 438-455, 2018.
• Habib A, Sawmiller D, Hou H, Kanithi M, Tian J, Zeng J, Zi D, He ZX, Sanberg PR, Tan J. Human Cord Blood Serum-Derived APP α-Secretase Cleavage Activity is Mediated by C1 Complement. Cell transplantation. 27(4) : 666-676, 2018.
• Leon M, Sawmiller D, Shytle RD, Tan J. Therapeutic Cocktail Approach for Treatment of Hyperhomocysteinemia in Alzheimer''s Disease. Cell medicine. 10: 2155179017722280, 2018.
• 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.
• Habib A, Sawmiller D, Tan J. Restoring Soluble Amyloid Precursor Protein α Functions as a Potential Treatment for Alzheimer''s Disease. Journal of neuroscience research. 95(4) : 973-991, 2017.
• Hou H, Habib A, Zi D, Tian K, Tian J, Giunta B, Sawmiller D, Tan J. Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro. Neuromolecular medicine. 19(2-3) : 300-308, 2017.
• Pérez C, Sawmiller D, Tan J. The role of heparan sulfate deficiency in autistic phenotype: potential involvement of Slit/Robo/srGAPs-mediated dendritic spine formation. Neural development. 11: 11, 2016.
• 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.
• Ehrhart J, Darlington D, Kuzmin-Nichols N, Sanberg CD, Sawmiller DR, Sanberg PR, Tan J. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer''s Disease-Like Murine Model. Cell transplantation. 25(1) : 195-9, 2016.
• Deng J, Habib A, Obregon DF, Barger SW, Giunta B, Wang YJ, Hou H, Sawmiller D, Tan J. Soluble amyloid precursor protein alpha inhibits tau phosphorylation through modulation of GSK3β signaling pathway. Journal of neurochemistry. 135(3) : 630-7, 2015.
• Darlington D, Li S, Hou H, Habib A, Tian J, Gao Y, Ehrhart J, Sanberg PR, Sawmiller D, Giunta B, Mori T, Tan J. Human umbilical cord blood-derived monocytes improve cognitive deficits and reduce amyloid-β pathology in PSAPP mice. Cell transplantation. 24(11) : 2237-50, 2015.
• Li S, Hou H, Mori T, Sawmiller D, Smith A, Tian J, Wang Y, Giunta B, Sanberg PR, Zhang S, Tan J. Swedish mutant APP-based BACE1 binding site peptide reduces APP β-cleavage and cerebral Aβ levels in Alzheimer''s mice. Scientific reports. 5: 11322, 2015.
• Li S, Deng J, Hou H, Tian J, Giunta B, Wang Y, Sawmiller D, Smith A, Sanberg PR, Obregon D, Mori T, Tan J. Specific antibody binding to the APP672-699 region shifts APP processing from α- to β-cleavage. Cell death & disease. 5: e1374, 2014.
• Sawmiller D, Li S, Shahaduzzaman M, Smith AJ, Obregon D, Giunta B, Borlongan CV, Sanberg PR, Tan J. Luteolin reduces Alzheimer''s disease pathologies induced by traumatic brain injury. International journal of molecular sciences. 15(1) : 895-904, 2014.
• Wang C, Li M, Sawmiller D, Fan Y, Ma Y, Tan J, Ren Y, Li S. Chronic mild stress-induced changes of risk assessment behaviors in mice are prevented by chronic treatment with fluoxetine but not diazepam. Pharmacology, biochemistry, and behavior. 116: 116-28, 2014.
• Sawmiller DR, Fenton RA, Dobson JG. Myocardial adenosine A1 and A2 receptor activities during juvenile and adult stages of development. The American journal of physiology. 271(1 Pt 2) : H235-43, 1996.
• Luthin DR, Olsson RA, Thompson RD, Sawmiller DR, Linden J. Characterization of two affinity states of adenosine A2a receptors with a new radioligand, 2-[2-(4-amino-3-[125I]iodophenyl)ethylamino]adenosine. Molecular pharmacology. 47(2) : 307-13, 1995.
• Sawmiller DR, Linden J, Berne RM. Effects of xanthine amine congener on hypoxic coronary resistance and venous and epicardial adenosine concentrations. Cardiovascular research. 28(5) : 604-9, 1994.
• Nguyen HT, Sawmiller DR, Markov O, Chen M. Elevated [Ca2+]i levels occur with decreased calpain activity in aged fibroblasts and their reversal by energy-rich compounds: new paradigm for Alzheimer''s disease prevention. Journal of Alzheimer''s disease : JAD. 37(4) : 835-48, 2013.
• Sawmiller DR, Chou CC. Role of adenosine in postprandial and reactive hyperemia in canine jejunum. The American journal of physiology. 263(4 Pt 1) : G487-93, 1992.
• Zhang SQ, Obregon D, Ehrhart J, Deng J, Tian J, Hou H, Giunta B, Sawmiller D, Tan J. Baicalein reduces β-amyloid and promotes nonamyloidogenic amyloid precursor protein processing in an Alzheimer''s disease transgenic mouse model. Journal of neuroscience research. 91(9) : 1239-46, 2013.
• Sawmiller DR, Chou CC. Adenosine is a vasodilator in the intestinal mucosa. The American journal of physiology. 261(1 Pt 1) : G9-15, 1991.
• Sawmiller DR, Chou CC. Jejunal adenosine increases during food-induced jejunal hyperemia. The American journal of physiology. 258(3 Pt 1) : G370-6, 1990.
• Zhou R, Zhou H, Cui M, Wang Y, Tan J, Sawmiller D, Xu J. Association between aortic calcification and the risk of osteoporosis in a chinese cohort: the Chongqing osteoporosis study. Calcified tissue international. 93(5) : 419-25, 2013.
• Sawmiller DR, Chou CC. Adenosine plays a role in food-induced jejunal hyperemia. The American journal of physiology. 255(2 Pt 1) : G168-74, 1988.
• Alemayehu A, Sawmiller D, Chou BS, Chou CC. Intestinal prostacyclin and thromboxane production in irreversible hemorrhagic shock. Circulatory shock. 23(2) : 119-30, 1987.
• 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.
• Habib A, Deng J, Hou H, Zou Q, Giunta B, Wang YJ, Obregon D, Sawmiller D, Li S, Mori T, Tan J. Mycoplasma hyorhinis markedly degrades β-amyloid peptides in vitro and ex vivo: a novel biological approach for treating Alzheimer''s disease? American journal of translational research. 5(6) : 634-42, 2013.
• Sawmiller DR, Nguyen HT, Markov O, Chen M. High-energy compounds promote physiological processing of Alzheimer''s amyloid-β precursor protein and boost cell survival in culture. Journal of neurochemistry. 123(4) : 525-31, 2012.
• Henning RJ, Dennis S, Sawmiller D, Hunter L, Sanberg P, Miller L. Human umbilical cord blood mononuclear cells activate the survival protein Akt in cardiac myocytes and endothelial cells that limits apoptosis and necrosis during hypoxia. Translational research : the journal of laboratory and clinical medicine. 159(6) : 497-506, 2012.
• Nguyen HT, Sawmiller DR, Wu Q, Maleski JJ, Chen M. Evidence supporting the role of calpain in the α-processing of amyloid-β precursor protein. Biochemical and biophysical research communications. 420(3) : 530-5, 2012.
• Chen M, Nguyen HT, Sawmiller DR. What to look for beyond "pathogenic" factors in senile dementia? A functional deficiency of Ca²⁺ signaling. Journal of Alzheimer''s disease : JAD. 27(4) : 679-89, 2011.
• Chen M, Maleski JJ, Sawmiller DR. Scientific truth or false hope? Understanding Alzheimer''s disease from an aging perspective. Journal of Alzheimer''s disease : JAD. 24(1) : 3-10, 2011.
• Henning RJ, Aufman J, Shariff M, Sawmiller D, DeLostia V, Sanberg P, Morgan M. Human umbilical cord blood mononuclear cells decrease fibrosis and increase cardiac function in cardiomyopathy. Regenerative medicine. 5(1) : 45-54, 2010.
• Sawmiller DR, Ashtari M, Urueta H, Leschinsky M, Henning RJ. Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the isolated perfused rat heart. Neuropeptides. 40(5) : 349-55, 2006.
• Sawmiller DR, Henning RJ, Cuevas J, Dehaven WI, Vesely DL. Coronary vascular effects of vasoactive intestinal peptide in the isolated perfused rat heart. Neuropeptides. 38(5) : 289-97, 2004.
• Tarpey SB, Sawmiller DR, Kelly C, Thompson WJ, Townsley MI. Phosphodiesterase 3 activity is reduced in dog lung following pacing-induced heart failure. American journal of physiology. Lung cellular and molecular physiology. 284(5) : L766-73, 2003.
• Henning RJ, Sawmiller DR. Vasoactive intestinal peptide: cardiovascular effects. Cardiovascular research. 49(1) : 27-37, 2001.
• Monahan TS, Sawmiller DR, Fenton RA, Dobson JG. Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts. American journal of physiology. Heart and circulatory physiology. 279(4) : H1472-81, 2000.
• Sawmiller DR, Fenton RA, Dobson JG. Myocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation. The American journal of physiology. 274(2) : H627-35, 1998.
• Dobson JG, Fenton RA, Sawmiller DR. The contractile response of the ventricular myocardium to adenosine A1 and A2 receptor stimulation. Annals of the New York Academy of Sciences. 793: 64-73, 1996.