Khalid Elased, Pharm.D., Ph.D.

Department:
Pharmacology & Toxicology-SOM
Title:
Professor, Pharmacology & Toxicology
Address:
Health Sciences Bldg 238, 3640 Colonel Glenn Hwy., Dayton, OH 45435-0001

Research Interests

Mechanisms of Disease-Diabetes and Chronic Kidney Disease.

My current research interests focus on:

1- Understanding and manipulating the Renin-Angiotensin System (RAS) relevant to hypertension and diabetes. 

2- Use of MALDI- TOF-MS and  SELDI-TOF-MS to develop and optimize miniaturized novel assays for quantitative evaluation of localized and circulating RAS. 

2- Our recent work focused on the development of urinary Angiotensin Converting Enzyme (ACE2 ) and neprilysin (NEP) as biomarkers for early detection of Chronic Kidney Disease in diabetic patients.

Our laboratory uses radiotelemetry, confocal microscopy, western blot and enzyme assay to investigate the effect of hyperglycemia on blood pressure, renal RAS and progression of CKD  in murine model of diabetes and hypertension.

Previous research interests were focused on extraction, purification and characterization of insulin mimetic molecules from Plasmodium yoelii. These molecules are related to Glycosylphosphatiylinositos (GPIs) which could have a potential as new antidiabetic agents.

Research is funded by NHLBI, American Heart Association, WSU Boonshoft School of Medicine.

 

Patents:

 1. Treatment of diabetes:

              British Patent Application No. 9618290.2

              Inventor: Elased KM, De Souza JB & Playfair JHL

              Patent Number: WO98/09637, March, 1998, Patent Number: US 6,214,357, April 2001

2. Phosphoglycan messengers and their medical uses (lipidemia).

               Inventors: Elased KM, Gumaa KA, De Souza JB, Rahmoune, H & Rademacher TW        

              British Patent Application No. 0015627.3. Filed on 26th June 2000

              Published in Patents & Designs Journal (16 August 2000 No. 5805: 3559)

3. Phosphoglycan messengers and their medical uses (SLE).

              Inventors: Elased KM, Gumaa KA, De Souza JB, Rahmoune H & Rademacher TW

              British Patent Application No. 0012563.2. Filed on 26th June 2000

              Published in Patents & Designs Journal (16 August 2000 No. 5805: 3559).

4. Screening Assay for Enzymes Involved in Patho-physiology Using SELDI-TOF Mass Spectrometry

              Inventors: Elased KM & Morris M.

             Attorney Docket No. WRU 0269 PA/40878.369,

             US Patent Application Serial No: 11/292,806. Filed on December 2, 2005

5. Screening Assay for Inhibitors of Severe Acute Respiratory Syndrome (SARS) Using SELDI-TOF Mass Spectrometry. Inventors: Elased KM & Morris M

             US Patent Application Serial No: 11/433,050. Filed on May 12, 2006

            Patent granted on February 2008 (US Patent no. 7,332,296)

 

Education History

Doctorate of Pharmacy (Pharm.D.)

Ohio Northern University, School of Pharmacy, Ada, Ohio, USA.

Doctorate of Pharmacology (Ph.D.)

University of Strathclyde, School of Pharmacy, Glasgow, Scotland, UK.

Thesis: Stress-induced hyperinsulinemia.

Advisor: Professor Brian Furman.

Master of Science in Physiology & Pharmacology (MSc)

University of Bradford, School of Pharmacy, England, UK.

Thesis: Role of myofibroblasts in wound healing.Advisor: Professor Ian Naylor.

Bachelor of Pharmacy (B.Pharm.)

University of Khartoum, School of Pharmacy, SudanUniversity of Khartoum, School of Pharmacy, Sudan

 

Publications

  1. The IL-8-CXCR1/2 axis contributes to diabetic kidney disease.

Loretelli C, Rocchio F, D'Addio F, Ben Nasr M, Castillo-Leon E, Dellepiane S, Vergani A, Abdelsalam A, Assi E, Maestroni A, Usuelli V, Bassi R, Pastore I, Yang J, El Essawy B, Elased KM, Fadini GP, Ippolito E, Seelam AJ, Pezzolesi M, Corradi D, Zuccotti GV, Gallieni M, Allegretti M, Niewczas MA, Fiorina P. Metabolism. 2021 Aug;121:154804. doi: 10.1016/j.metabol.2021.154804. Epub 2021 Jun 10.PMID: 34097917

  1. Effects of Angiotensin II Type 1A Receptor on ACE2, Neprilysin and KIM-1 in Two Kidney One Clip (2K1C) Model of Renovascular Hypertension.

Alawi LF, Dhakal S, Emberesh SE, Sawant H, Hosawi A, Thanekar U, Grobe N, Elased KM. Front Pharmacol. 2021 Jan 29;11:602985. doi: 10.3389/fphar.2020.602985. eCollection 2020.PMID: 33708117 

  1. Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin in db/db diabetic mice.

Alawi LF, Emberesh SE, Owuor BA, Chodavarapu H, Fadnavis R, El-Amouri SS, Elased KM. Physiol Rep. 2020 Feb;8(3):e14364. doi: 10.14814/phy2.14364.PMID: 32026607.

  1. Type 2 Diabetes Leads to Axon Initial Segment Shortening in db/db Mice.

Yermakov LM, Drouet DE, Griggs RB, Elased KM, Susuki K. Front Cell Neurosci. 2018 Jun 8;12:146. doi: 10.3389/fncel.2018.00146. eCollection 2018.PMID: 29937715.

  1. Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes.

Gutta S, Grobe N, Kumbaji M, Osman H, Saklayen M, Li G, Elased KM. Am J Physiol Renal Physiol. 2018 Aug 1;315(2):F263-F274. doi: 10.1152/ajprenal.00565.2017. Epub 2018 Mar 21.PMID: 29561187.

  1. Analysis of Angiotensin Metabolism in the Kidney Using Mass Spectrometry.

Grobe N, Elased KM. Methods Mol Biol. 2017;1614:189-197. doi: 10.1007/978-1-4939-7030-8_15.PMID: 28500605

  1. Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney.

Domenig O, Manzel A, Grobe N, Königshausen E, Kaltenecker CC, Kovarik JJ, Stegbauer J, Gurley SB, van Oyen D, Antlanger M, Bader M, Motta-Santos D, Santos RA, Elased KM, Säemann MD, Linker RA, Poglitsch M. Sci Rep. 2016 Sep 21;6:33678. doi: 10.1038/srep33678.PMID: 27649628.

  1. A highly efficient strategy to determine genotypes of genetically-engineered mice using genomic DNA purified from hair roots.

Otaño-Rivera V, Boakye A, Grobe N, Almutairi MM, Kursan S, Mattis LK, Castrop H, Gurley SB, Elased KM, Boivin GP, Di Fulvio M. Lab Anim. 2017 Apr;51(2):138-146. doi: 10.1177/0023677216646088. Epub 2016 Jul 10.PMID: 27166392.

  1. Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells.

Grobe N, Di Fulvio M, Kashkari N, Chodavarapu H, Somineni HK, Singh R, Elased KM. Am J Physiol Cell Physiol. 2015 May 1;308(9):C767-77. doi: 10.1152/ajpcell.00247.2014. Epub 2015 Mar 4.PMID: 25740155.

  1. Loss of prolyl carboxypeptidase in two-kidney, one-clip goldblatt hypertensive mice.

Grobe N, Leiva O, Morris M, Elased KM. PLoS One. 2015 Feb 23;10(2):e0117899. doi: 10.1371/journal.pone.0117899. eCollection 2015.PMID: 25706121.

  1. Biomechanical properties and histology of db/db diabetic mouse Achilles tendon.

Boivin GP, Elenes EY, Schultze AK, Chodavarapu H, Hunter SA, Elased KM. Muscles Ligaments Tendons J. 2014 Nov 17;4(3):280-4. eCollection 2014 Jul. PMID: 25489543.

  1. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

Sharma AN, Ligade SS, Sharma JN, Shukla P, Elased KM, Lucot JB. Metab Brain Dis. 2015 Apr;30(2):519-27. doi: 10.1007/s11011-014-9591-7. Epub 2014 Jul 15.PMID: 25023888

  1. Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 shedding in db/db diabetic mice.

Somineni HK, Boivin GP, Elased KM.J Endocrinol. 2014 Apr 22;221(2):235-51. doi: 10.1530/JOE-13-0532. Print 2014 May. PMID: 24756098.

  1. Novel role of aminopeptidase-A in angiotensin-(1-7) metabolism post myocardial infarction.

Alghamri MS, Morris M, Meszaros JG, Elased KM, Grobe N. Am J Physiol Heart Circ Physiol. 2014 Apr 1;306(7):H1032-40. doi: 10.1152/ajpheart.00911.2013. Epub 2014 Jan 24.PMID: 24464749.

  1. Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice.

Salem ES, Grobe N, Elased KM. Am J Physiol Renal Physiol. 2014 Mar 15;306(6):F629-39. doi: 10.1152/ajprenal.00516.2013. Epub 2014 Jan 22.PMID: 24452639.

  1. Diabetic db/db mice exhibit central nervous system and peripheral molecular alterations as seen in neurological disorders.

Ernst A, Sharma AN, Elased KM, Guest PC, Rahmoune H, Bahn S. Transl Psychiatry. 2013 May 28;3(5):e263. doi: 10.1038/tp.2013.42.PMID: 23715298.

  1. Rosiglitazone treatment of type 2 diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion.

Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One. 2013 Apr 30;8(4):e62833. doi: 10.1371/journal.pone.0062833. Print 2013.PMID: 23646149.

  1. Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis.

Dixit TS, Sharma AN, Lucot JB, Elased KM. Physiol Behav. 2013 Apr 10;114-115:38-41. doi: 10.1016/j.physbeh.2013.03.008. Epub 2013 Mar 21.PMID: 23523479

  1. Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry.

Grobe N, Weir NM, Leiva O, Ong FS, Bernstein KE, Schmaier AH, Morris M, Elased KM. Am J Physiol Cell Physiol. 2013 May 15;304(10):C945-53. doi: 10.1152/ajpcell.00346.2012. Epub 2013 Feb 7.PMID: 23392115.

  1. Enhanced angiotensin II-induced cardiac and aortic remodeling in ACE2 knockout mice.

Alghamri MS, Weir NM, Anstadt MP, Elased KM, Gurley SB, Morris M.J Cardiovasc Pharmacol Ther. 2013 Mar;18(2):138-51. doi: 10.1177/1074248412460124. Epub 2012 Oct 5.PMID: 23043153

  1. Effects of restricted fructose access on body weight and blood pressure circadian rhythms.

Senador D, Shewale S, Irigoyen MC, Elased KM, Morris M. Exp Diabetes Res. 2012;2012:459087. doi: 10.1155/2012/459087. Epub 2012 Mar 29.PMID: 22536215.

  1. Rosiglitazone treatment reversed depression- but not psychosis-like behavior of db/db diabetic mice.

Sharma AN, Elased KM, Lucot JB. J Psychopharmacol. 2012 May;26(5):724-32. doi: 10.1177/0269881111434620. Epub 2012 Feb 12.PMID: 22331176

  1. Mass spectrometry for the molecular imaging of angiotensin metabolism in kidney.

Grobe N, Elased KM, Cool DR, Morris M. Am J Physiol Endocrinol Metab. 2012 Apr 15;302(8):E1016-24. doi: 10.1152/ajpendo.00515.2011. Epub 2012 Feb 7.PMID: 22318946.

  1. Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness.

Agbor LN, Elased KM, Walker MK. Biochem Pharmacol. 2011 Sep 1;82(5):514-23. doi: 10.1016/j.bcp.2011.06.011. Epub 2011 Jun 13.PMID: 21684261.

  1. Neurobehavioral deficits in db/db diabetic mice.

Sharma AN, Elased KM, Garrett TL, Lucot JB. Physiol Behav. 2010 Oct 5;101(3):381-8. doi: 10.1016/j.physbeh.2010.07.002. Epub 2010 Jul 14.PMID: 20637218.

  1. Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Kopf PG, Scott JA, Agbor LN, Boberg JR, Elased KM, Huwe JK, Walker MK. Toxicol Sci. 2010 Oct;117(2):537-46. doi: 10.1093/toxsci/kfq218. Epub 2010 Jul 15.PMID: 20634294.

  1. An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice.

Zhang N, Agbor LN, Scott JA, Zalobowski T, Elased KM, Trujillo A, Duke MS, Wolf V, Walsh MT, Born JL, Felton LA, Wang J, Wang W, Kanagy NL, Walker MK. Biochem Pharmacol. 2010 Jul 15;80(2):197-204. doi: 10.1016/j.bcp.2010.03.023. Epub 2010 Mar 30.PMID: 20359465.

  1. Cardiovascular interactions between losartan and fructose in mice.

Senador D, Key M, Brosnihan KB, Irigoyen MC, Elased KM, Morris M.J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):68-77. doi: 10.1177/1074248409351409. Epub 2009 Dec 7.PMID: 19995939.

  1. Cardiovascular and autonomic phenotype of db/db diabetic mice.

Senador D, Kanakamedala K, Irigoyen MC, Morris M, Elased KM. Exp Physiol. 2009 Jun;94(6):648-58. doi: 10.1113/expphysiol.2008.046474. Epub 2009 Feb 13.PMID: 19218356.

  1. Brain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in mice.

Elased KM, Cunha TS, Marcondes FK, Morris M. Exp Physiol. 2008 May;93(5):665-75. doi: 10.1113/expphysiol.2007.040311. Epub 2008 Feb 8.PMID: 18263657.

  1. Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet.

Farah V, Elased KM, Morris M. Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1083-9. doi: 10.1152/ajpheart.00106.2006. Epub 2007 Apr 20.PMID: 17449556

  1. Relationship between renal and cardiovascular changes in a murine model of glucose intolerance.

Cunha TS, Farah V, Paulini J, Pazzine M, Elased KM, Marcondes FK, Cláudia Irigoyen M, De Angelis K, Mirkin LD, Morris M. Regul Pept. 2007 Mar 1;139(1-3):1-4. doi: 10.1016/j.regpep.2006.11.023. Epub 2007 Jan 4.PMID: 17207869

  1. Nocturnal hypertension in mice consuming a high fructose diet.

Farah V, Elased KM, Chen Y, Key MP, Cunha TS, Irigoyen MC, Morris M. Auton Neurosci. 2006 Dec 30;130(1-2):41-50. doi: 10.1016/j.autneu.2006.05.006. Epub 2006 Jul 13.PMID: 16843071

  1. New mass spectrometric assay for angiotensin-converting enzyme 2 activity.

Elased KM, Cunha TS, Gurley SB, Coffman TM, Morris M. Hypertension. 2006 May;47(5):1010-7. doi: 10.1161/01.HYP.0000215588.38536.30. Epub 2006 Apr 3.PMID: 16585421

  1. Novel mass spectrometric methods for evaluation of plasma angiotensin converting enzyme 1 and renin activity.

Elased KM, Cool DR, Morris M. Hypertension. 2005 Oct;46(4):953-9. doi: 10.1161/01.HYP.0000174601.30793.b1. Epub 2005 Aug 15.PMID: 16103259

  1. Improvement of glucose homeostasis in obese diabetic db/db mice given Plasmodium yoelii glycosylphosphatidylinositols.

Elased KM, Gumaa KA, de Souza JB, Playfair JH, Rademacher TW. Metabolism. 2004 Aug;53(8):1048-53. doi: 10.1016/j.metabol.2004.03.013.PMID: 15281017

  1. Reversal of type 2 diabetes in mice by products of malaria parasites. II. Role of inositol phosphoglycans (IPGs).

Elased KM, Gumaa KA, de Souza JB, Rahmoune H, Playfair JH, Rademacher TW. Mol Genet Metab. 2001 Jul;73(3):248-58. doi: 10.1006/mgme.2001.3186.PMID: 11461192

  1. Reversal of type 2 diabetes in mice by products of malaria parasites: I. Effect of inactivated parasites.

Elased KM, de Souza JB, Playfair JH. Metabolism. 2000 Jul;49(7):937-41. doi: 10.1053/meta.2000.6756.PMID: 10910007

  1. Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice.

Elased KM, Taverne J, Playfair JH. Clin Exp Immunol. 1996 Sep;105(3):443-9. doi: 10.1046/j.1365-2249.1996.d01-781.x.PMID: 8809132.

  1. Malaria toxins: TNF-mediated phenomena.

Taverne J, Sheikh N, Elased K, Playfair J, Scott M, Saggerson D. Parasitol Today. 1996 Jul;12(7):290. doi: 10.1016/0169-4758(96)80817-9.PMID: 15275196 No abstract available.

  1. Reversal of hypoglycaemia in murine malaria by drugs that inhibit insulin secretion.

Elased KM, Playfair JH. Parasitology. 1996 Jun;112 ( Pt 6):515-21. doi: 10.1017/s0031182000066087.PMID: 8684825

  1. Malaria toxins: hypoglycaemia and TNF production are induced by different components.

Taverne J, Sheikh N, Elased K, Playfair J. Parasitol Today. 1995 Dec;11(12):462-3; author reply 463. doi: 10.1016/0169-4758(95)80060-3.PMID: 15275384 No abstract available.

  1. Blood-stage malaria infection in diabetic mice.

Elased K, De Souza JB, Playfair JH. Clin Exp Immunol. 1995 Mar;99(3):440-4. doi: 10.1111/j.1365-2249.1995.tb05570.x.PMID: 7882567.

  1. Hypoglycemia and hyperinsulinemia in rodent models of severe malaria infection.

Elased K, Playfair JH. Infect Immun. 1994 Nov;62(11):5157-60. doi: 10.1128/iai.62.11.5157-5160.1994.PMID: 7927799.

  1. Acute stress-induced hyperinsulinemia in the pertussis toxin-treated rat: possible role of humoral beta-cell-tropic factors.

Elased KM, Furman BL. Metabolism. 1994 Oct;43(10):1221-5. doi: 10.1016/0026-0495(94)90214-3.PMID: 7934972

Professional Affiliations/Memberships

PROFESSIONAL SOCIETY MEMBERSHIP:

2014- Present: Member of the American Society of Physiology (ASP).

2013- Present: Member of the American Society of Nephrology (ASN).

2011- Present: Member of the American College of Clinical Pharmacy (ACCP).

2010- Present:  Delegate of Boonshoft School of Medicine to the United States Pharmacopeia (USP) Conventions.

2008- Elected Fellow in the American Heart Association (AHA) Council of High Blood Pressure.  

2005- 2009: Member of the American Society for Pharmacology and Experimental Therapeutics (ASPET).

2004- Present: Member of the American Heart Association (AHA). 

1999- Present: Member of the American Diabetic Association (ADA).

1990- Present: Member of the European Association for the Study of Diabetes (EASD).

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