Nadja Grobe, Ph.D.
Our laboratory studies complex hormonal peptide pathways involved in renal physiology and in the development of chronic kidney disease. It is well documented that the activation of the renin angiotensin system and increase of angiotensin II contribute to the pathophysiology of chronic kidney disease. The goal is to understand how manipulation of the renin angiotensin system and angiotensin II pathways may attenuate progression of renal disease and promote renoprotection in patients through improved diagnostic tools and targeted treatment strategies.
To better understand the complex hormonal peptide pathways of the renin angiotensin system we established a new mass spectrometric imaging approach for the localization of in situ enzyme activity on tissue sections. Using this powerful mass spectrometric technique and genetic mouse models, we explore the complex mechanisms by which the peptide hormones of the renin angiotensin system are formed and metabolized locally in the kidney.
Other routinely used techniques include renal and cardiovascular biomedical research techniques such as monitoring of renal, cardiovascular and metabolic parameters in conscious animals and small animal surgeries including placement of telemetry catheters for chronic blood pressure measurements, renal artery clips as a model of renal artery stenosis, and osmotic mini pumps for drug delivery.
- Alghamri MS, Morris M, Meszaros JG, Elased KE, Grobe N (2014). Novel role of aminopeptidase-A in angiotensin-(1-7) metabolism post myocardial infarction. Am J Physiol Heart Circ Physiol (in press).
- Salem ESB, Grobe N, Elased KM (2014). Insulin treatment attenuates renal ADAM17 and ACE2 shedding in Akita diabetic mice. Am J Physiol Renal Physiol (in press).
- Grobe N, Weir NM, Leiva O, Ong FS, Bernstein KE, Schmaier AH, Morris M, Elased KM (2013) Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry. Am J Physiol Cell Physiol 304 (10): C945-53. This article was featured in an Editorial Focus written by Velez JC (2013). Prolyl carboxypeptidase: a forgotten kidney angiotensinase. Am J Physiol Cell Physiol 304 (10): C939-40.
- Chodavarapu H, Grobe N, Somineni HK, Salem ESB, Madhu M, Elased KM (2013) Rosiglitazone treatment of diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion. PLOS ONE 8 (4): e62833.
- Fang C, Stavrou E, Schmaier AA, Grobe N, Morris M, Chen A, Nieman MT, Adams GN, LaRusch G, Zhou Y, Bilodeau ML, Mahdi F, Warnock M, Schmaier AH (2013). Angiotensin-(1-7) and Mas Decrease Thrombosis in Bradykinin B2 Receptor Knockout Mice by Increasing NO and Prostacyclin to Reduce Platelet Activation. Blood 121 (15): 3023-3032.
- Grobe N, Kutchan TM, Zenk MH (2012) Rat CYP2D2, not 2D1, is functionally conserved with human CYP2D6 in endogenous morphine formation. FEBS letters 586(13):1749-53.
- Grobe N, Elased KM, Cool DR, Morris M. (2012) Mass spectrometry for the molecular imaging of angiotensin metabolism in the kidney. Am J Physiol Endocrinol Metab Innovative Methodology 302 (8): E1016-1024.
- Lamshöft M, Grobe N, Spiteller, M (2011) Picomolar concentrations of morphine in human urine determined by dansyl derivatization and liquid chromatography-mass spectrometry. Journal of Chromatography B 879(13-14): 933-937.
- Grobe N, Ren X, Kutchan TM, Zenk MH (2011) An (R)-specific N-methyltransferase involved in human morphine biosynthesis. Archives of Biochemistry and Biophysics 506 (1): 42-47.
- Lamshöft M, Grobe N (2010) Mäuseproduzieren endogenes Morphin (Mice produce endogenous morphine). GIT Spezial, Separation 1/2010: 18-20.
- Han X, Lamshöft M, Grobe N, Ren X, Fist AJ, Kutchan TM, Spiteller M, Zenk MH (2010) The biosynthesis of papaverine proceeds via (S)-reticuline. Phytochemistry 71 (11-12): 1305-1312.
- Grobe N, Lamshöft M, Orth RG, Dräger B, Kutchan TM, Zenk MH, Spiteller M (2010) Urinary excretion of morphine and biosynthetic precursors in mice. PNAS 107 (18): 8147-8152.
- Grobe N, Zhang B, Fisinger U, Kutchan TM, Zenk MH, Guengerich FP (2009) Mammalian cytochrome P450 enzymes catalyze the phenol-coupling step in endogenous morphine biosynthesis. Journal of Biological Chemistry 284 (36): 24425-24431.
- Fisinger U, Grobe N, Zenk MH (2007) Thebaine synthase: A new enzyme in the morphine pathway in Papaver somniferum. Natural Products Communications 2(3): 249-253.
M.S. in Biochemistry (2005), Martin-Luther-University Halle-Wittenberg, Germany
Ph.D. in Biological Sciences (2009), Martin-Luther-University Halle-Wittenberg, Germany
Postdoctoral (2010-2013), Wright State University Boonshoft School of Medicine