Blood-Brain Barrier; Brain; Brain Chemistry; Brain Diseases, Metabolic; Cognition; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Hypoglycemia; Magnetic Resonance Imaging; Metabolism; Magnetic Resonance Spectroscopy; Nuclear Magnetic Resonance, Biomolecular; Proteomics; Diabetes Complications; Metabolomics
Dr. Raimund Herzog is an Assistant Professor in Endocrinology at Yale School of Medicine. He received his M.D. from University of Ulm, Germany before moving to the US, where he pursued his training in Internal Medicine at Yale School of Medicine. He earned his M.H.S. in the YCCI Junior Faculty Scholars program while further specializing in Endocrinology at Yale. In addition to caring for patients at the Yale Diabetes Center and teaching medical students Dr. Herzog maintains an active translational research program. A physician scientist with a strong interest in neuroscience and diabetes Dr. Herzog’s laboratory is focused on characterizing and preventing its central nervous complications. He uses state-of-the-art technologies like in vivo NMR spectroscopy and phospho-proteomics to define the impact of diabetes and intensive insulin treatment on brain metabolism and cognition. His work extends from cell culture and animal models all the way to translation of findings to human subjects with diabetes. It has produced novel insights into the molecular mechanisms underlying brain energy substrate metabolism thereby laying the basis for the development of targeted therapies that will protect the brain from diabetes complications and injury.
In a related area Dr. Herzog’s workgroup has engaged in several collaborative projects that apply his understanding of metabolism towards more comprehensive and unbiased metabolomic analysis of peripheral plasma metabolites in an obese and diabetic adolescent cohort. Furthermore he is exploring the role of circulating small molecules and lipids in the context of aging-related cognitive decline in a cohort of elderly subjects. As part of these studies he has established a close working relationship with the Keck Mass Spectrometry Center and the Biostatistics Resource at Yale. His studies are funded by several NIH and private foundation awards and have resulted in high impact publications in journals like The Journal of Clinical Investigation, Diabetes and Endocrinology.
Extensive Research Description
- Adaptations of Brain Energy Metabolism to Hypoglycemia
- Regulation of Brain Glucose Metabolism by Alternate Fuels
Diabetes: Can tight glycemic control in diabetes benefit cognition?
Herzog, R.I. and R.S. Sherwin, Diabetes: Can tight glycemic control in diabetes benefit cognition? Nat Rev Neurol, 2012. 8(3): p. 124-126.
Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia.
Herzog, R. I., L. Jiang, P. Herman, C. Zhao, B. G. Sanganahalli, G. F. Mason, F. Hyder, D. L. Rothman, R. S. Sherwin and K. L. Behar (2013). Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest 123(5): 1988-1998
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor.
Xiang, Y., J. Cheng, D. Wang, X. Hu, Y. Xie, J. Stitham, G. Atteya, J. Du, W. H. Tang, S. H. Lee, K. Leslie, G. Spollett, Z. Liu, E. Herzog, R. I. Herzog, J. Lu, K. A. Martin and J. Hwa (2015). Blood 125(22): 3377-3387.
Quantification of 1H NMR spectra from human plasma.
de Graaf, R., H. Prinsen, C. Giannini, S. Caprio and R. Herzog (2015). Metabolomics: 1-6.
Full List of PubMed Publications
- De Feyter HM, Herzog RI, Steensma BR, Klomp DWJ, Brown PB, Mason GF, Rothman DL, de Graaf RA: Selective proton-observed, carbon-edited (selPOCE) MRS method for measurement of glutamate and glutamine 13 C-labeling in the human frontal cortex. Magn Reson Med. 2017 Nov 13; 2017 Nov 13. PMID: 29134686
- Kinser ER, Padmanabhan J, Yu R, Corona SL, Li J, Vaddiraju S, Legassey A, Loye A, Balestrini J, Solly DA, Schroers J, Taylor AD, Papadimitrakopoulos F, Herzog RI, Kyriakides TR: Nanopatterned Bulk Metallic Glass Biosensors. ACS Sens. 2017 Nov 8; 2017 Nov 8. PMID: 29115132
- Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G: Extracellular Mitochondrial DNA is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017 Aug 7; 2017 Aug 7. PMID: 28783377
- Tricò D, Prinsen H, Giannini C, de Graaf R, Juchem C, Li F, Caprio S, Santoro N, Herzog RI: Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents. J Clin Endocrinol Metab. 2017 Jul 1. PMID: 28482070
- Goffredo M, Santoro N, Tricò D, Giannini C, D'Adamo E, Zhao H, Peng G, Yu X, Lam TT, Pierpont B, Caprio S, Herzog RI: A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease. Nutrients. 2017 Jun 22; 2017 Jun 22. PMID: 28640216
- Tricò D, Herzog RI: Metabolic brain adaptations to recurrent hypoglycaemia may explain the link between type 1 diabetes mellitus and epilepsy and point towards future study and treatment options. Diabetologia. 2017 May; 2017 Feb 24. PMID: 28236055
- Tricò D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog RI, Johnson CD, Umano GR, Feldstein AE, Santoro N: Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxid Redox Signal. 2017 Apr 7; 2017 Apr 7. PMID: 28279074
- Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD: β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Rep. 2017 Feb 28. PMID: 28249154
- Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI, Lin S, Horsley V, Carpenter TO, Chung C: Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB J. 2016 Aug; 2016 Apr 28. PMID: 27127101
- de Graaf RA, Prinsen H, Giannini C, Caprio S, Herzog RI: Quantification of 1H NMR Spectra from Human Plasma. Metabolomics. 2015 Dec; 2015 Jul 5. PMID: 26526515
- Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J: Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood. 2015 May 28; 2015 Mar 26. PMID: 25814526
- Gurr W, Shaw M, Herzog RI, Li Y, Sherwin R: Vaccination with single chain antigen receptors for islet-derived peptides presented on I-A(g7) delays diabetes in NOD mice by inducing anergy in self-reactiveT-cells. PLoS One. 2013; 2013 Jul 24. PMID: 23894487
- Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL: Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest. 2013 May; 2013 Apr 1. PMID: 23543056
- Herzog RI, Sherwin RS: Diabetes. Can tight glycemic control in diabetes benefit cognition? Nat Rev Neurol. 2012 Jan 31; 2012 Jan 31. PMID: 22290574
- Herzog RI, Sherwin RS, Rothman DL: Insulin-induced hypoglycemia and its effect on the brain: unraveling metabolism by in vivo nuclear magnetic resonance. Diabetes. 2011 Jul. PMID: 21709281
- Jiang L, Herzog RI, Mason GF, de Graaf RA, Rothman DL, Sherwin RS, Behar KL: Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo. Diabetes. 2009 Jun; 2009 Mar 10. PMID: 19276443
- Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS: Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration. Endocrinology. 2008 Apr; 2008 Jan 10. PMID: 18187548
- Leffler A, Herzog RI, Dib-Hajj SD, Waxman SG, Cummins TR: Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflugers Arch. 2005 Dec; 2005 Jun 25. PMID: 15981012
- Cummins TR, Dib-Hajj SD, Herzog RI, Waxman SG: Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons. FEBS Lett. 2005 Apr 11. PMID: 15811336
- Herzog RI, Cummins TR, Ghassemi F, Dib-Hajj SD, Waxman SG: Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J Physiol. 2003 Sep 15; 2003 Jul 3. PMID: 12843211
- Herzog RI, Liu C, Waxman SG, Cummins TR: Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J Neurosci. 2003 Sep 10. PMID: 12967988
- Cummins TR, Renganathan M, Stys PK, Herzog RI, Scarfo K, Horn R, Dib-Hajj SD, Waxman SG: The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology. 2003 Jan 28. PMID: 12552035
- Herzog RI, Cummins TR, Waxman SG: Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. J Neurophysiol. 2001 Sep. PMID: 11535682
- Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, Waxman SG: Nav1.3 sodium channels: rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons. J Neurosci. 2001 Aug 15. PMID: 11487618
- Uhl W, Herzog RI, Sadowski C, Krähenbühl L, Maurer CA, Büchler MW: [Surgical therapy of ileus of the small intestine]. Zentralbl Chir. 1998. PMID: 10063542