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July 2013 Researcher of the Month - Michaele Manigrasso, PhD

Michaele Manigrasso, PhDCurrent Studies
Diabetes-associated nephropathy affects 30-40% of subjects with type 1 diabetes (T1D). Furthermore, progression to end-stage renal failure is a serious complication of this disorder and leads to an increased morbidity and mortality. Our laboratory group has identified that a potential target for prevention and treatment of T1D-associated nephropathy is the receptor for advanced glycation endproducts (RAGE).

While multiple strategies targeting RAGE are in various stages of pre-clinical and early clinical development, including soluble forms of the extracellular domain of RAGE, anti-RAGE antibodies and small molecule antagonists which selectively target the binding of RAGE ligands to the cell surface receptor, my current research is to examine a new area of RAGE research and focus on the interaction of the cytoplasmic domain of RAGE with diaphanous-1 (mDia-1) and it’s contribution to the development of podocyte dysfunction and the pathogenesis of diabetic nephropathy in T1D.


Publications
1.  Manigrasso MB. Diabetes and vascular disease: sex matters. Vascular Pharmacology 2012; 57(2-4): 78-80.

2.  Maric-Bilkan C and Manigrasso MB. Sex differences in hypertension: contribution of the renin-angiotensin system. Gender Medicine 2012; 9(4):287-91

3.  Manigrasso MB, Sawyer RT, Hutchens ZM Jr, Flynn ER, Maric-Bilkan C.  Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats. Am J Physiol-Renal Physiol 2012; 302(9):F1203-09.

4.  Barsony J, Manigrasso MB, Xu Q, Tam H, Verbalis JG.  Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. AGE (Dordr) 2013 Apr;35(2):271-88. doi: 10.1007/s11357-011-9347-9. Epub 2012 Jan 5.

5.  Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Inhibition of estradiol synthesis attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats. Am J Physiol-Renal Physiol 2011; 301(3):F634-40.

6.   Liu J, Sharma N, Zheng W, Ji H, Tam H, Wu X, Manigrasso MB, Sandberg K, Verbalis JG.  Sex differences in vasopressin V2 receptor expression and vasopressin-induced antidiuresis. Am J Physiol-Renal Physiol 2011; 300(2):F433-40.

7.  Manigrasso MB, O’Connor JP.  Accelerated fracture healing in mice lacking the 5- lipoxygenase gene. Acta Orthopaedica 2010; 81(6):748-755.

8.  Venegas-Pont M, Manigrasso MB, Grifoni SC, Lamarca BB, Maric C, Racusen LC, Glover PH, Jones AV, Drummond HA, Ryan MJ. Tumor necrosis factor-{alpha} antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus. Hypertension 2010; 56(4):643-649.

9.  Prabhu A, Xu Q, Manigrasso MB, Biswas M, Flynn E, Iliescu R, Lephart ED, Maric C.  Expression of aromatase, androgen and estrogen receptors in peripheral target tissues in diabetes.  Steroids 2010; 75(11):779-787.

10.  O’Connor JP, Capo JT, Tan V, Cottrell JA, Manigrasso MB, Bontempo N, Parsons JR.  A comparison of Ibuprofen and rofecoxib effects on rabbit fibula osteotomy healing.  Acta Orthopaedica 2009; 80(5):597-605.

11.  Xu Q, Prabhu A, Xu S, Manigrasso MB, Maric C.  Dose-dependent effects of dihydrotestosterone in the streptozotocin-induced diabetic rat kidney. Am J Physiol-Renal Physiol 2009; 297(2):F307-315.

12.  Capo JT, Kinchelow T, Brooks K, Tan V, Manigrasso M, Francisco K.  Biomechanical stability of four fixation constructs for distal radius fractures.  Hand (NY) 2009; 4(3):272-278.

13.  Garman JH, Mulroney S, Manigrasso M, Flynn E, Maric, C.  Omega-3 fatty acid rich diet prevents diabetic renal disease.  Am J Physiol-Renal Physiol 2009; 296(2): F306-316.

14.  Manigrasso MB, O’Connor JP.  Comparison of fracture healing among different inbred mouse strains.  Calcif Tissue Int. 2008; 82(6): 465-474.

15.  Manigrasso MB, O’Connor JP.  Characterization of a closed femur fracture model in mice.  J. Orthop Trauma 2004; 18(10): 687-695.

16.  Simon AM, Manigrasso MB, O’Connor JP.  Cyclo-oxygenase 2 function is essential for bone fracture healing.  J Bone Miner Res 2002; 17(6):963-976.


Book Chapters
1.  Manigrasso MB and Maric-Bilkan C. Peptides, Sex, Diabetes and the Kidney. In “The Handbook of Biologically Active Peptides, 2nd edition” Ed-in-Chief Kastin A published by Elsevier. In Press.


Selected Meeting Abstracts and Presentations:
1.  Manigrasso, MB, Ganda A, Rosario R, Hurtado del Pozo C, Song F, Ananthakrishnan R, D’Agati V, Ramasamy R and Schmidt AM. Aldose reductase and RAGE: key mechanisms in the pathogenesis of diabetic nephropathy in murine models. American Diabetes Association’s 73rd Scientific Sessions, Chicago, IL June 2013.

2.   Manigrasso MB, Davis DD, Lu S, Xiang L and Hester RL.  Orthopedic trauma reduces renal hemodynamics in the STZ-induced diabetic rat. Experimental Biology Annual Scientific Meeting, San Diego, CA April 2012.

3.  Manigrasso MB, Sawyer RT, Hutchens ZM Jr, Flynn ER and Maric C. Androgen receptor (AR) and estrogen receptor alpha (ERα) expression after combined dihydrotestosterone (DHT) supplementation and aromatase inhibition in the male streptozotocin (STZ)- induced diabetic rat. 2011 APS Conference, Physiology of Cardiovascular Disease: Gender Disparities, Jackson, MS Oct. 2011.

4.  Manigrasso MB, Sawyer RT, Hutchens ZM Jr, Flynn ER and Maric C.  Dual treatment with dihydrotestosterone and an aromatase inhibitor provides renoprotection in male streptozotocin (STZ)-induced diabetic rats. The 6th Gulf Coast Physiology Society Meeting, Jackson, MS May 2011.

5.  Manigrasso MB, Sawyer RT, Flynn ER and Maric C.  Renoprotective effects of dual treatment with dihydrotestosterone and an aromatase inhibitor in male streptozotocin-induced diabetic rats. Experimental Biology Annual Scientific Meeting, Washington, DC April 2011.

6.  Manigrasso MB, Marbury DC, Sawyer RT, Flynn ER, Maric C.  Inhibition of estradiol synthesis attenuates diabetic renal disease in male streptozotocin (STZ)-induced diabetic rats.  Experimental Biology Annual Scientific Meeting, Anaheim, CA April 2010.

7.  Maric C, Manigrasso MB.  Beneficial effects of inhibiting estradiol synthesis in experimental model of diabetic renal disease.  4th Congress of the International Society of Gender Medicine.  Berlin, Germany. November 2009.

8.  Maric C, Manigrasso MB, Marbury DC, Chade AR.  Decrease in renal microvascular density precedes the decline in renal function in STZ-induced diabetic rats. American Society of Nephrology- Renal Week 2009.  San Diego, CA October 2009.

9.   Liu J, Tam H, Zheng W, Hong J, Sharma N, Wu X, Manigrasso MB, Sandberg K, Verbalis JG. Sex differences in vasopressin V2 receptor expression and vasopressin-induced antidiuresis.  American Society of Nephrology- Renal Week 2009.  San Diego, CA October 2009.

10.  Manigrasso MB, Lephart ED, Maric C.  Extra-testicular origin of estradiol in diabetes.  APS Conference on Sex Steroids and Gender in Cardiovascular-Renal Physiology and Pathophysiology.  Broomfield, CO, July 2009.

11.  Barsony J, Manigrasso M, Tam H, Sugimura Y, Tian Y, Verbalis JG.  Chronic hyponatremia induces severe bone lose and mild hypogonadism in both male and female rats.  91st Annual Meeting of the Endocrine Society (ENDO 2009).  Washington, DC. June 2009.

12.  Barsony J, Manigrasso M, Tam H, Xu Q, Sugimura Y, Tian Y, Adams D, Carter EA, Resnick HE,  Verbalis JG.  Hyponatremia-induced osteoporosis.  38th Annual Meeting of the American Aging Association.  Scottsdale, AZ.  May 2009.

13.  Barsony J, Manigrasso MB, Tam H, Doshi AH, Verbalis JG.  Hyponatremia induces bone loss and prevents fat accumulation in aged F344 Brown Norway rats.  29th Annual Meeting of the American Society for Bone and Mineral Research. Honolulu, HI.  September, 2007.

14.  Manigrasso MB, France M, Tauro J.  Cyclic loading of a double-row knotless fixation system for arthroscopic rotator cuff repair:  A biomechanical evaluation.  Arthroscopic Association of North America (AANA).  May 2006.

15.  Manigrasso MB and O’Connor JP.  Accelerating fracture healing by manipulating arachidonic acid metabolism. 52nd Annual Meeting of the Orthopaedic Research Society.  Chicago, IL. March, 2006.

16.  Capo JT, Manigrasso MB, Honig K, Tan V. Peri-articular soft tissue anatomy of the elbow.  Joint Annual Meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists, San Antonio, TX. September 2005.

17.  Meier SW and Manigrasso MB.  Rotator cuff repair: The effect of double-row fixation on tendon-bone motion at the repair interface.  Arthroscopic Association of North America (AANA).  Vancouver, Canada. May 2005.

18.  Meier SW and Manigrasso MB.  Rotator cuff repair: The effect of double-row fixation on initial repair strength.  5th Biennial International Society of Arthroscopy, Knee Surgery and Orthopedic Sports Medicine (ISAKOS), Hollywood, FL. April 2005.

19.  Meier SW, Meier J, Levy A and Manigrasso MB.  Rotator cuff repair: The effect of double-row fixation on three-dimensional repair Site.  23rd Annual Arthroscopy Association of North America (AANA), Orlando, FL. April 2004.

20.  Meier SW, Meier J, Levy A and Manigrasso MB.  Rotator cuff repair: The effect of double-row fixation on three-dimensional repair Site.  23rd Annual Arthroscopy Association of North America (AANA), Orlando, FL. April 2004.


Future Plans
I hope to combine my previous research examining gender in diabetes with my current project at the Diabetes Research Program to explore the role of RAGE and inflammation in the pathogenesis of type1 diabetes in both males and females.

Most importantly, the training that I continue to receive through pursuing these studies will contribute to my development into an independent investigator dedicated to research for finding the cure of end-organ complications associated with type 1 diabetes.