William A Dunn

William A Dunn, PhD

Professor

Department: MD-ANATOMY
Business Phone: (352) 273-9007
Business Email: dunn@ufl.edu

Teaching Profile

Courses Taught
2013-2014,2016-2019,2018-2023
GMS6635 Organization of Cells and Tissues
2011-2013,2018-2024
GMS6690 Molecular Cell Biology Journal Club
2019-2024
GMS5057 Medical Cell Biology
2013-2024
GMS5630 Medical Histology
2013-2014,2016-2023
GMS6001 Fundamentals of Biomedical Sciences I
2013-2014,2019-2023
BMS6031 Foundations of Med
2020-2024
GMS6691 Special Topics in Cell Biology and Anatomy
2020-2024
BMS6632 Endo and Reproduction
2014,2016-2020,2020-2024
GMS6421 Cell Biology
2017,2019-2024
BMS4136C Human Histology
2018
GMS7979 Advanced Research
2018
GMS7980 Research for Doctoral Dissertation
2014,2016-2018
GMS6062 Protein Trafficking
2018
BMS6300 Fund Micro and Immuno
2016-2017
GMS6647 Transcriptional and Translational Control of Cell Growth and Proliferation
2016
GMS6644 Apoptosis
2015,2024
BMS6638C Kidney & Urinary Tract
2014,2021-2023
GMS6692 Research Conference in Anatomy and Cell Biology
2021
GMS6063 Cell Biology of Aging
2022-2024
DEN5126C Histology
2024
BMS6642 The Resp Sys Hlth
2024
BMS6633 The Cv System

Research Profile

Eukaryotic cells adapt to environmental changes by altering their protein complements through synthesis and degradation. Cells that adapt poorly or improperly may either cease to exist (e.g., apoptosis) or become neoplastic (e.g., hepatoma). Cells adapt to low levels of amino acids by sequestering proteins and organelles for lysosomal degradation via a process called autophagy. The data suggest that autophagy protects the cells from nutrient, environmental, and chemical stresses that may cause cell death. Autophagy-mediated cell protection is likely mediated by the degradation of damaged mitochondria, which otherwise would promote cell death via apoptosis. The ability of autophagy to remove and degrade damaged mitochondria also suggests that autophagy may have a beneficial role in aging. Furthermore, cancers that effectively regulate autophagy have the potential to resist chemotherapy agents and thrive. In addition, it appears that some bacteria utilize the autophagy pathway of the host cell to escape lysosomal destruction thereby replicating within the host. Finally, we have shown that autophagy may be a major pathway for the removal of protein aggregates observed in many neuropathies and in aged cells. On the other hand, autophagy can promote cell death. Our long-term goals are to characterize the molecular aspects of the regulation and mechanisms of cellular autophagy in normal and diseased tissues. We have identified by in silico docking and powerful cellular screening methods “first-in-class” compounds that either inhibit or activate the autophagy response in mammalian cells. We currently plan to utilize these unique compounds to establish autophagy as a therapeutic target for treating cancer and other diseases. We are combining our understanding of the molecular events of autophagy with novel autophagy compounds to design clinical approaches by which to turn off autophagy and suppress the survival of chemoresistant cancers and promote the degradation of intracellular pathogens or to turn on autophagy and arrest neoplastic growth, degrade protein aggregates, and remove damaged mitochondria during aging and ishemia/reperfusion.

RESEARCH PROJECTS

Molecular Characterization of Autophagy: We are utilizing a multidisciplinary approach of cell, molecular, and genetic procedures to establish the functional roles of specific cellular proteins in selective and nonselective autophagy in mammalian cells.

The Role of Autophagy in Cancer: In collaboration with Drs. Yehia Daaka (Dept. of Anatomy and Cell Biology) and Brian Law (Dept. of Pharmacology and Therapeutics), we are utilizing genetic and pharmaceutical approaches to evaluate the role of autophagy in cell survival and cell death and in tumor growth of breast, prostate, kidney, pancreas, and liver.

Interactions between Oral Pathogens and Vascular Cells: In collaboration with Dr. Ann Progulske-Fox (Dept. of Oral Biology, College of Dentistry), we are utilizing both morphologic and genetic approaches to characterize the events of bacterial invasion in vascular endothelial cells.

Role of Autophagy in Aging: In collaboration with Drs. John Aris (Dept. of Anatomy and Cell Biology), Christiaan Leeuwenburg (Dept. of Aging and Geriatric Research) and Jae-Sung Kim (Dept. of Zoology), we are investigating in a rat aging model the autophagic responses to aging in different tissues and if autophagy can suppress aging by removing damaged mitochondria.

Role of Autophagy in Organ Transplants: In collaboration with Dr. Kim (Dept. of Surgery), we are evaluating the role of autophagy in cell death during ischemia /reperfusion.

Role of Autophagy in the Removal of Protein Aggregates: In collaboration with Dr. Lucia Notterpek (Dept. of Neuroscience), we are examining avenues by which to promote the removal and degradation of PMP22 protein aggregates by autophagy in cell and animal models of hereditary peripheral neuropathies.

Role of Autophagy in Retinal Function: In collaboration with Drs. Maria Grant and Michael Boulton (University of Indiana), we are examining the role of autophagy is the circadian rhythm and homeostasis of the retina.

Open Researcher and Contributor ID (ORCID)

0000-0002-0577-3913

Publications

2017
Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.
PloS one. 12(2) [DOI] 10.1371/journal.pone.0171940. [PMID] 28222108.
2016
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Autophagy. 12(1):1-222 [DOI] 10.1080/15548627.2015.1100356. [PMID] 26799652.
2016
Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.
Cell death and differentiation. 23(2):279-90 [DOI] 10.1038/cdd.2015.96. [PMID] 26184910.
2014
A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.
Autophagy. 10(11):2021-35 [DOI] 10.4161/auto.32229. [PMID] 25483883.
2014
Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.
Autophagy. 10(11):1989-2005 [DOI] 10.4161/auto.36184. [PMID] 25484094.
2014
Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice.
Neurobiology of disease. 70:224-36 [DOI] 10.1016/j.nbd.2014.06.023. [PMID] 25014022.
2013
Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast.
Experimental gerontology. 48(10):1107-19 [DOI] 10.1016/j.exger.2013.01.006. [PMID] 23337777.
2013
Deletion of lipoprotein PG0717 in Porphyromonas gingivalis W83 reduces gingipain activity and alters trafficking in and response by host cells.
PloS one. 8(9) [DOI] 10.1371/journal.pone.0074230. [PMID] 24069284.
2013
Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity.
Autophagy. 9(3):328-44 [DOI] 10.4161/auto.22971. [PMID] 23298947.
2012
Amino acid homeostasis and chronological longevity in Saccharomyces cerevisiae.
Sub-cellular biochemistry. 57:161-86 [DOI] 10.1007/978-94-007-2561-4_8. [PMID] 22094422.
2012
Autophagy in the retina: a potential role in age-related macular degeneration.
Advances in experimental medicine and biology. 723:83-90 [DOI] 10.1007/978-1-4614-0631-0_12. [PMID] 22183319.
2012
Hydrogen Sulfide Reduces Gfp-Tagged Autophagosomes in Vitro
The FASEB's Journal. 26
2012
Porphyromonas gingivalis strain specific interactions with human coronary artery endothelial cells: a comparative study.
PloS one. 7(12) [DOI] 10.1371/journal.pone.0052606. [PMID] 23300720.
2011
Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of mice.
Gastroenterology. 141(6):2188-2199.e6 [DOI] 10.1053/j.gastro.2011.08.005. [PMID] 21854730.
2010
Overexpression of Atg4B and Beclin-1 Enhances Liver Mitochondrial-Autophagy and Prevents the Age-Associated Ischemia/Reperfusion Injury To Mouse Liver
Higher Education Policy. 52
2010
Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(34):11388-97 [DOI] 10.1523/JNEUROSCI.1356-10.2010. [PMID] 20739560.
2009
Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae.
Aging cell. 8(4):353-69 [DOI] 10.1111/j.1474-9726.2009.00469.x. [PMID] 19302372.
2009
Autophagy is required for extension of yeast chronological life span by rapamycin.
Autophagy. 5(6):847-9 [PMID] 19458476.
2009
Identification of Compounds That Enhance and Suppress Autophagy
Autophagy. 5:910-911
2009
Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease.
Neurobiology of disease. 34(1):146-54 [PMID] 19320048.
2009
Invasion of human coronary artery endothelial cells by Streptococcus mutans OMZ175.
Oral microbiology and immunology. 24(2):141-5 [DOI] 10.1111/j.1399-302X.2008.00487.x. [PMID] 19239641.
2009
Using LC3 to monitor autophagy flux in the retinal pigment epithelium.
Autophagy. 5(8):1190-3 [PMID] 19855195.
2008
Changes in autophagy proteins in a rat model of controlled cortical impact induced brain injury.
Biochemical and biophysical research communications. 373(4):478-81 [DOI] 10.1016/j.bbrc.2008.05.031. [PMID] 18486600.
2008
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.
Autophagy. 4(2):151-75 [PMID] 18188003.
2008
Impaired Autophagy Contributes To Resistance of Cirrhotic Liver-Derived Hepatocytes To Transforming Growth Factor Beta (Tgf Beta)-Induced Apoptosis
Higher Education Policy. 48
2008
Impaired autophagy: A mechanism of mitochondrial dysfunction in anoxic rat hepatocytes.
Hepatology (Baltimore, Md.). 47(5):1725-36 [DOI] 10.1002/hep.22187. [PMID] 18311843.
2008
Porphyromonas gingivalis and the autophagic pathway: an innate immune interaction?
Frontiers in bioscience : a journal and virtual library. 13:178-87 [PMID] 17981536.
2008
Porphyromonas Gingivalis and the Autophagic Pathway: An Innate Immune Interaction?
The Journal of pharmacy and pharmacology. 13(12):178-187 [DOI] 10.2741/2668. [PMID] 2668.
2008
Porphyromonas gingivalis htrA is involved in cellular invasion and in vivo survival.
Microbiology (Reading, England). 154(Pt 4):1161-1169 [DOI] 10.1099/mic.0.2007/015131-0. [PMID] 18375808.
2008
The membrane dynamics of pexophagy are influenced by Sar1p in Pichia pastoris.
Molecular biology of the cell. 19(11):4888-99 [PMID] 18768759.
2007
Autophagy in the heart and liver during normal aging and calorie restriction.
Rejuvenation research. 10(3):281-92 [PMID] 17665967.
2007
Developmental abnormalities in the nerves of peripheral myelin protein 22-deficient mice.
Journal of neuroscience research. 85(2):238-49 [PMID] 17131416.
2007
How shall I eat thee?
Autophagy. 3(5):413-6 [PMID] 17568180.
2007
Identification of pexophagy genes by restriction enzyme-mediated integration.
Methods in molecular biology (Clifton, N.J.). 389:203-18 [PMID] 17951645.
2007
The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones.
Neurobiology of disease. 25(2):252-65 [PMID] 17174099.
2007
The Porphyromonas gingivalis clpB gene is involved in cellular invasion in vitro and virulence in vivo.
FEMS immunology and medical microbiology. 51(2):388-98 [PMID] 17854400.
2006
Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression.
Neurobiology of disease. 22(1):153-64 [PMID] 16326107.
2006
Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1.
Apoptosis : an international journal on programmed cell death. 11(9):1573-82 [PMID] 16703260.
2006
Autophagy: a highway for Porphyromonas gingivalis in endothelial cells.
Autophagy. 2(3):165-70 [PMID] 16874051.
2006
Early and late molecular events of glucose-induced pexophagy in Pichia pastoris require Vac8.
Autophagy. 2(4):280-8 [PMID] 16921262.
2006
Peripheral myelin protein 22 is in complex with alpha6beta4 integrin, and its absence alters the Schwann cell basal lamina.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(4):1179-89 [PMID] 16436605.
2006
PpAtg9 trafficking during micropexophagy in Pichia pastoris.
Autophagy. 2(1):52-4 [PMID] 16874077.
2005
Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis.
Arteriosclerosis, thrombosis, and vascular biology. 25(3):e17-8 [PMID] 15662025.
2005
Pexophagy: the selective autophagy of peroxisomes.
Autophagy. 1(2):75-83 [PMID] 16874024.
2005
PpATG9 encodes a novel membrane protein that traffics to vacuolar membranes, which sequester peroxisomes during pexophagy in Pichia pastoris.
Molecular biology of the cell. 16(10):4941-53 [PMID] 16079180.
2003
A unified nomenclature for yeast autophagy-related genes.
Developmental cell. 5(4):539-45 [PMID] 14536056.
2003
Atg23 is essential for the cytoplasm to vacuole targeting pathway and efficient autophagy but not pexophagy.
The Journal of biological chemistry. 278(48):48445-52 [PMID] 14504273.
2003
Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy.
Molecular biology of the cell. 14(2):477-90 [PMID] 12589048.
2003
Emerging role for autophagy in the removal of aggresomes in Schwann cells.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(33):10672-80 [PMID] 14627652.
2002
Bacterial interactions with the autophagic pathway.
Cellular microbiology. 4(1):1-10 [PMID] 11856168.
2001
Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris.
Molecular biology of the cell. 12(12):3821-38 [PMID] 11739783.
2001
Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole.
The Journal of cell biology. 153(2):381-96 [PMID] 11309418.
2001
Interaction between aldolase and vacuolar H+-ATPase: evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump.
The Journal of biological chemistry. 276(32):30407-13 [PMID] 11399750.
2001
Porphyromonas gingivalis traffics to autophagosomes in human coronary artery endothelial cells.
Infection and immunity. 69(9):5698-708 [PMID] 11500446.
2001
Starvation-induced lysosomal degradation of aldolase B requires glutamine 111 in a signal sequence for chaperone-mediated transport.
Journal of cellular physiology. 187(1):48-58 [PMID] 11241348.
2000
Dissection of autophagosome biogenesis into distinct nucleation and expansion steps.
The Journal of cell biology. 151(5):1025-34 [PMID] 11086004.
1999
Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a unique E1-like protein.
Molecular biology of the cell. 10(5):1353-66 [PMID] 10233149.
1999
Invasion of human coronary artery cells by periodontal pathogens.
Infection and immunity. 67(11):5792-8 [PMID] 10531230.
1999
Ubiquitinated aldolase B accumulates during starvation-induced lysosomal proteolysis.
Journal of cellular physiology. 178(1):17-27 [PMID] 9886486.
1997
Glucose-induced microautophagy in Pichia pastoris requires the alpha-subunit of phosphofructokinase.
Journal of cell science. 110 ( Pt 16):1935-45 [PMID] 9296392.
1995
Divergent modes of autophagy in the methylotrophic yeast Pichia pastoris.
Journal of cell science. 108 ( Pt 1):25-35 [PMID] 7738102.
1994
Autophagy and related mechanisms of lysosome-mediated protein degradation.
Trends in cell biology. 4(4):139-43 [PMID] 14731737.
1994
Growth factor-induced neurite growth in primary neuronal cultures of dogs with neuronal ceroid lipofuscinosis.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 12(3):185-96 [PMID] 7942092.
1993
Selective autophagy of peroxisomes in methylotrophic yeasts.
European journal of cell biology. 60(2):283-90 [PMID] 8330626.
1992
A novel mechanism for isoprenaline-stimulated proliferation of rat parotid acinar cells involving the epidermal growth factor receptor and cell surface galactosyltransferase.
The Biochemical journal. 284 ( Pt 3)(Pt 3):767-76 [PMID] 1622394.
1992
Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles.
Journal of cellular physiology. 152(3):458-66 [PMID] 1506410.
1992
Effects of streptozotocin-induced diabetes on rough endoplasmic reticulum and lysosomes of rat liver.
The American journal of physiology. 263(5 Pt 1):E856-62 [PMID] 1443117.
1992
Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum.
The Journal of cell biology. 117(5):959-73 [PMID] 1374417.
1992
Ubiquitin-activating enzyme, E1, is associated with maturation of autophagic vacuoles.
The Journal of cell biology. 118(2):301-8 [PMID] 1321157.
1991
Identification of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced endometriosis in rats.
Obstetrics and gynecology. 78(5 Pt 1):850-7 [PMID] 1923211.
1991
Regulation of protein secretion by crinophagy in perfused rat liver.
European journal of cell biology. 56(2):201-9 [PMID] 1724960.
1990
Studies on the mechanisms of autophagy: formation of the autophagic vacuole.
The Journal of cell biology. 110(6):1923-33 [PMID] 2351689.
1990
Studies on the mechanisms of autophagy: maturation of the autophagic vacuole.
The Journal of cell biology. 110(6):1935-45 [PMID] 2161853.

Grants

Mar 2020 – Jun 2021
Integrated transcriptomics and metabolomics approach to define pathogenicity of P.gingivalis
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDCR
Dec 2019 ACTIVE
Investigating the viable but not culturable (VBNC) state in P. gingivalis
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDCR
Jul 2019 – Jun 2020
The American Society for Cell Biology Early Career Meeting Grant Application Requirements
Role: Project Manager
Funding: AMERICAN SOCIETY FOR CELL BIOLOGY
Apr 2015 – Mar 2021
P. gingivalis mediated disruption of autophagy in endothelial dysfunction
Role: Project Manager
Funding: NATL INST OF HLTH NHLBI
Jul 2013 – Dec 2016
Internalization of S. mutans in vascular endothelial cells
Role: Project Manager
Funding: NATL INST OF HLTH NIDCR
Dec 2012 – Dec 2018
Research fund- Anatomy & cell Biology
Role: Principal Investigator
Funding: UF FOUNDATION

Education

PhD
1979 · Pennsylvania State University, University Park, PA
BA
1974 · Thiel College, Greenville, PA

Contact Details

Phones:
Business:
(352) 273-9007
Emails:
Business:
dunn@ufl.edu
Addresses:
Business Mailing:
PO Box 100235
GAINESVILLE FL 32610
Business Street:
1200 Newell Drive
ARB R4-228
Department of Anatomy & Cell Biology
GAINESVILLE FL 326100235