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George Biosketch

OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 09/30/2024)

BIOGRAPHICAL SKETCH

NAME: Eric M George
eRA COMMONS USER NAME (credential, e.g., agency login): egeorge
POSITION TITLE: Associate Professor of Physiology and Biophysics
EDUCATION/TRAINING

Personal Statement
My major areas of research interest are in gestational disorders, in particular preeclampsia and gestational hypertension. As the etiology and pathophysiology of preeclampsia are still poorly understood, my lab is primarily focused on understanding the downstream effects of placental insufficiency and ischemia-believed to be the central mechanism driving the symptomatic phase of the disorder.

Recently, the primary focus of the lab has been in determining the relevance of ischemia-driven production of extracellular remodeling factors. Notably this includes overproduction of the enzymes heparanase and matrix metalloproteinases which can act on the placental and maternal glycocalyx. Currently, we are examining the biological effects of the cleavage products of these enzymes, and determining their role in innate inflammatory factor production and immune cell infiltration. We have further identified a number of novel anti-angiogenic peptides produced by ischemic placental tissue which have not been previously described and we are actively investigating the biological mechanisms underlying them and their relevance in both our pre-clinical rodent model and the utility of these peptides as a biomarker in our UMC patient population.

Positions, Scientific Appointments, and Honors

Professional Experience

2019-present Associate Professor, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS

2013-2019 Assistant Professor, Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS

2013-present Graduate Faculty, School of Graduate Studies in the Health Sciences

2013-present Assistant Professor, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS

2009-present Member, UMMC Women’s Health Research Center, Jackson, MS

2009-present Member, UMMC Cardiovascular and Renal Research Center, Jackson, MS

2009-2013 Postdoctoral Fellow, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS

2002-2010 Graduate Student, Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS

Other Experience and Professional Memberships

2009 – Present Member, American Physiological Society

2009 – Present Member, American Heart Association

2010 – Present Member of the Research Trainee Advisory Subcommittee for the AHA’s Council on High Blood Pressure

2011 – Present Reviewer for AHA Summer Undergraduate Research Fellowship Grants

2013 – Present Member, University of Mississippi Medical Center School of Graduate Studies in the Health Sciences Alumni Board of Directors

2014 – 2015 Cardiovascular and Renal Research Center Seminar Director

2014 – Present Reviewer for the Intramural Research Support Program (IRSP), University of Mississippi Medical Center

2015 – Present Member, University of Mississippi Medical Center Postdoctoral Advisory Committee

2015 – Present Department of Physiology and Biophysics Seminar Director

2015 – Present External Reviewer for French National Research Agency

2015 – 2020 Editorial Board Member, Obstetric and Pediatric Pharmacology

2015 – 2017 Faculty Advisor, Trainee Advocacy Committee, APS Sex and Gender Research Interest Group

2020 – Present Director, Graduate Program, Department of Physiology and Biophysics, University of Mississippi Medical Center

Awards

2010 American Heart Association Hypertension Summer School Travel Award

2011 American Heart Association HBPR Trainee Advocacy New Investigator Travel Award

2014 University of Mississippi Medical Center Excellence in Research Award – Bronze Medal

2015 University of Mississippi Medical Center Excellence in Research Award – Silver Medal

2016 APS WEH New Investigator Award

2016 APS Early Career Advocacy Fellowship

2018 University of Mississippi Medical Center Excellence in Research Award-Gold Medal

Contributions to Science

My basic science interests are in the elucidation of the basic molecular mechanisms which link placental ischemia and the maternal syndrome of preeclampsia. Recently these have been in the area of the placental extracellular matrix and its role in regulating angiogenic factors in preeclampsia. Other topics have ranged from transcriptional analysis to reveal novel mechanisms regulating VEGF in the placenta, targeted studies to determine the importance of phosphodiesterases in the kidney during preeclampsia, and molecular mechanisms underlying alternative splicing of sFlt-1. A number of these studies have provided basis for ongoing research in both my lab and in other institutions.

Selected Publications

1. Moore KH, Murphy HA, Chapman H, and George EM. Syncytialization alters the extracellular matrix and barrier function of placental trophoblasts. Am J Physiol Cell Physiol. 2021 Aug 18.
2. Moore KH, Murphy HA, and George EM. The Glycocalyx: A Central Regulator of Vascular Function. Am J Physiol Regul Integr Comp Physiol. 2021 Jan 27.
3. Moore KH, Chapman H, and George EM. Unfractionated heparin displaces sFlt-1 from the placental extracellular matrix. Biol Sex Diff. 2020 Jun. 11:34. PMC7325113.
4. Eddy AE, Chapman H, Brown DT, and George EM. Differential Regulation of sFlt-1 Splicing by U2AF65 and JMJD6 in Placental Derived and Endothelial Cells. BioScience Reports. 2020 Feb 25:40(2). PMC7042122.

I have a long-running collaboration between myself and Dr. Lee Bidwell. In concert, our laboratories have been developing novel peptide based therapeutics for the management of obstetrical complications. This system uniquely excludes transfer of attached therapies across the maternal/fetal interface, making administration of any agent much safer for the developing embryo. Though the carrier is robust enough for administration of any agent, we have begun primarily with potential therapies for preeclampsia, and have developed several angiogenic and anti-inflammatory agents, several of which are currently undergoing preclinical testing. This collaboration has been fruitful, with multiple publications, and an issued patent has been granted for the composition of the carrier and several specific agents.

Selected Publications

1. Waller JP, Howell JA, Peterson H, George EM, Bidwell GL 3rd.Elastin-Like Polypeptide: VEGF-B Fusion Protein for Treatment of Preeclampsia. 2021 Nov 1. PMC8585700.
2. Eddy AC, Howell JA, Chapman H, Taylor E, Mahdi F, George EM, and Bidwell GL. Biopolymer-Delivered, maternally Sequestered NF-KB Inhibitory Peptide for Treatment of Preeclampsia. Hypertension. Dec 2, 2019. PMC7008946.
3. George, E. M., Liu, H., Robinson, G., and Bidwell, G. L. III. A Polypeptide Drug Carrier for Maternal Delivery and Prevention of Fetal Exposure. Journal of Drug Targeting, 22:1-13, 2014. PMC4227969.
4. Logue OC, Mahdi F, Chapman H, George EM, and Bidwell GL. A Maternally Sequestered, biopolymer-stabilized Vascular Endothelial Growth Factor (VEGF) chimera for treatment of preeclampsia. J Am Heart Assoc. Dec 8, 2017. PMC5779036.

Patents

5. Bidwell, G.L. III, and George, E.M. “Composition And Method For Therapeutic Agent Delivery During Pregnancy.” US Patent 10,081,667. Issued 9/25/18.

The bulk of my post-doctoral training was attempting to utilize the heme oxygenase system to attenuate the maternal effects of placental-ischemia, a central causative factor in preeclampsia. This was a combination of basic science and applied therapeutics, as several of the downstream effectors of heme oxygenase we demonstrated had significant therapeutic potential. We also demonstrated an important role for endogenous heme oxygenase in normal gestation. This work has attracted a significant interest as a potential therapeutic avenue. This project resulted in 9 publications, with 8 as first author.

Selected Publications

1. George EM, Stec DE, and Granger JP. Heme oxygenase inhibition increases blood pressure in pregnant rats. Apr 3, 2013. Am J Hypertens;26(7):925-30. PMID23553216
2. George EM and Arany I. Induction of heme oxygenase-1 shifts the balance from pro-injury to pro-survival in the placentas of pregnant rats with reduced uterine perfusion pressure. Am J Physiol Regul Integr Comp Physiol. 2012 Mar 1;302(5):R620-6. PMID22237591.
3. George EM, Cockrell K., Arany M., Csongradi E., Stec D.E., and Granger J.P. Induction of Heme Oxygenase-1 Ameliorates Placental Ischemia-Induced Hypertension. Hypertension. 2011 May;57(5):941-8. Epub 2011 Mar 7.
4. George E.M., Arany M., Cockrell K., Storm M.V., Stec D.E., and Granger J.P. Induction of heme oxygenase-1 attenuates sFlt-1-induced hypertension in pregnant rats. Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1495-500. Epub 2011 Aug 24. PMID21865547.

My graduate work was concerned with chromatin structure and the role of linker histones in regulating gene expression. During the course of my doctoral work, I identified a previously unknown linker histone chaperone called prothymosin α, which has now been shown to be an important regulator of chromatin remodeling and a major factor in the DNA damage response. In addition, I used novel live-cell photobleaching techniques to study the interaction surfaces of linker histone H1 subtypes, and provided the first evidence that H1 subtype binding was not uniform, and could in fact cause dramatically different chromatin structures.

Selected Publications

1. George E.M. and Brown, D.T. Prothymosin α is a Component of a Linker Histone Chaperone. 2010. FEBS Letters. 2010 Jul 2;584(13):2833-6, PMID2891112.
2. George E.M., Izard, T., Anderson, S.D., and Brown, D.T. 2010. The Nucleosome Interaction Surface of Linker Histone H1c is Distinct from that of H1⁰. Journal of Biological Chemistry. 2010 Jul 2;285(27):20891-6, PMID2898364.
3. Hearst S.M., Gilder A.S., Negi S.S., Davis M.D., George E.M., Whittom A.A., Toyota C.G., Husedzinovic A., Gruss O.J., and Hebert, M.D. Cajal-body formation correlates with differential coilin phosphorylation in primary and transformed cell lines. The Journal of Cell Science. 2009 Jun 1;122(Pt 11):1872-81, PMID2684838.
4. Meshorer, E., Yellajoshula, D., George E, Scambler, P.J., Brown, D.T., and Misteli, T. 2006 Hyperdynamic Plasticity of Chromatin Proteins in Pluripotent Embryonic Stem Cells. 2006. Developmental Cell. 10(1): 105-116.

I have also been interested in developing anti-angiogenic compounds for ocular delivery. This could be a valuable approach for treating both corneal neovascularization and wet macular degeneration, as both are known to be heavily dependent on VEGF overactivity. We have developed a synthetic carrier which more readily crosses the cornea, and have recently submitted the first description of this work for publication.

Publications

1. 1. George EM, Mahdi F, Logue OC, Robinson GG, Bidwell GL III. “Corneal Penetrating Elastin-like Polypeptide Carriers. J Ocul Pharmacol Ther. 2016 Apr; 32(3):163-71. PMC in process.

Patents

1. Bidwell, G.L. III, and George, E.M. “Ocular Compositions and Methods Thereof.” Provisional patent filed April 29, 2014.

A full bibliography of 55 publications can be found at: https://www.ncbi.nlm.nih.gov/myncbi/123ToOPsZl_/bibliography/public/