Raimund Herzog, MD, MHS
Associate Professor of Medicine
Research & Publications
Biography
News
Research Summary
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
- Causes of Hypoglycemia Associated Autonomic Failure (HAAF) in T1DM
- Neuronal Regulation of Whole Body Glucose Homeostasis
- Biomarkers of Metabolic Decompensation in Different Patient Cohorts
Coauthors
Research Interests
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
Selected Publications
- O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth.Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, Li MD, Zhang K, Ding Z, Lee P, Singh K, Wu J, Herzog RI, Kaech S, Wendel HG, Yates JR, Han W, Sherwin RS, Nie Y, Yang X. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 2020, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.
- Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?Trico D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog R, 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? Antioxidants & Redox Signaling 2019, 30: 241-250. PMID: 28279074, PMCID: PMC6277079, DOI: 10.1089/ars.2017.7049.
- Mitochondrial MsrB2 serves as a switch and transducer for mitophagy.Lee SH, Lee S, Du J, Jain K, Ding M, Kadado AJ, Atteya G, Jaji Z, Tyagi T, Kim WH, Herzog RI, Patel A, Ionescu CN, Martin KA, Hwa J. Mitochondrial MsrB2 serves as a switch and transducer for mitophagy. EMBO Molecular Medicine 2019, 11: e10409. PMID: 31282614, PMCID: PMC6685081, DOI: 10.15252/emmm.201910409.
- Selective proton-observed, carbon-edited (selPOCE) MRS method for measurement of glutamate and glutamine 13 C-labeling in the human frontal cortex.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. Magnetic Resonance In Medicine : Official Journal Of The Society Of Magnetic Resonance In Medicine / Society Of Magnetic Resonance In Medicine 2018, 80: 11-20. PMID: 29134686, PMCID: PMC5876108, DOI: 10.1002/mrm.27003.
- Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation.Wang D, Hu X, Lee SH, Chen F, Jiang K, Tu Z, Liu Z, Du J, Wang L, Yin C, Liao Y, Shang H, Martin KA, Herzog RI, Young LH, Qian L, Hwa J, Xiang Y. Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation. JACC. Basic To Translational Science 2018, 3: 350-362. PMID: 30062222, PMCID: PMC6058960, DOI: 10.1016/j.jacbts.2018.01.005.
- Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents.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. The Journal Of Clinical Endocrinology And Metabolism 2017, 102: 2473-2481. PMID: 28482070, PMCID: PMC5505187, DOI: 10.1210/jc.2017-00475.
- A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease.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, 9 PMID: 28640216, PMCID: PMC5537762, DOI: 10.3390/nu9070642.
- Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis.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. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480OC.
- β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.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 Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.
- Nanopatterned Bulk Metallic Glass Biosensors.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 Sensors 2017, 2: 1779-1787. PMID: 29115132, DOI: 10.1021/acssensors.7b00455.
- 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.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, 60: 938-939. PMID: 28236055, PMCID: PMC5395303, DOI: 10.1007/s00125-017-4231-5.
- Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade.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 Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2016, 30: 2837-48. PMID: 27127101, PMCID: PMC4970601, DOI: 10.1096/fj.201500027R.
- Quantification of 1H NMR Spectra from Human Plasma.de Graaf RA, Prinsen H, Giannini C, Caprio S, Herzog RI. Quantification of 1H NMR Spectra from Human Plasma. Metabolomics : Official Journal Of The Metabolomic Society 2015, 11: 1702-1707. PMID: 26526515, PMCID: PMC4624446, DOI: 10.1007/s11306-015-0828-1.
- Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor.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, 125: 3377-87. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.
- 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.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, 8: e69464. PMID: 23894487, PMCID: PMC3722102, DOI: 10.1371/journal.pone.0069464.
- Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia.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. The Journal Of Clinical Investigation 2013, 123: 1988-98. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/JCI65105.
- Diabetes. Can tight glycemic control in diabetes benefit cognition?Herzog RI, Sherwin RS. Diabetes. Can tight glycemic control in diabetes benefit cognition? Nature Reviews. Neurology 2012, 8: 124-6. PMID: 22290574, PMCID: PMC5515668, DOI: 10.1038/nrneurol.2012.10.
- Insulin-induced hypoglycemia and its effect on the brain: unraveling metabolism by in vivo nuclear magnetic resonance.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, 60: 1856-8. PMID: 21709281, PMCID: PMC3121425, DOI: 10.2337/db11-0498.
- Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo.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, 58: 1266-74. PMID: 19276443, PMCID: PMC2682668, DOI: 10.2337/db08-1664.
- Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration.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, 149: 1499-504. PMID: 18187548, PMCID: PMC2276713, DOI: 10.1210/en.2007-1252.
- Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia.Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia. Diabetes 2008, 57: 1363-70. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.
- Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons.Cummins TR, Dib-Hajj SD, Herzog RI, Waxman SG. Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons. FEBS Letters 2005, 579: 2166-70. PMID: 15811336, DOI: 10.1016/j.febslet.2005.03.009.
- Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue.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. Pflügers Archiv : European Journal Of Physiology 2005, 451: 454-63. PMID: 15981012, DOI: 10.1007/s00424-005-1463-x.
- Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons.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. The Journal Of Physiology 2003, 551: 741-50. PMID: 12843211, PMCID: PMC2343279, DOI: 10.1113/jphysiol.2003.047357.
- The pentapeptide QYNAD does not block voltage-gated sodium channels.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, 60: 224-9. PMID: 12552035, DOI: 10.1212/01.wnl.0000042423.36650.bd.
- Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties.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. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2003, 23: 8261-70. PMID: 12967988, PMCID: PMC6740705.
- 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.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. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2001, 21: 5952-61. PMID: 11487618, PMCID: PMC6763143.
- Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons.Herzog RI, Cummins TR, Waxman SG. Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. Journal Of Neurophysiology 2001, 86: 1351-64. PMID: 11535682, DOI: 10.1152/jn.2001.86.3.1351.
- Glutamate-Serine-Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver Disease.Leonetti S, Herzog RI, Caprio S, Santoro N, Tricò D. Glutamate-Serine-Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver Disease. Children (Basel, Switzerland) 2020, 7 PMID: 33291552, PMCID: PMC7761842, DOI: 10.3390/children7120270.
- Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine.Cotero V, Graf J, Miwa H, Hirschstein Z, Qanud K, Huerta TS, Tai N, Ding Y, Jimenez-Cowell K, Tomaio JN, Song W, Devarajan A, Tsaava T, Madhavan R, Wallace K, Loghin E, Morton C, Fan Y, Kao TJ, Akhtar K, Damaraju M, Barenboim L, Maietta T, Ashe J, Tracey KJ, Coleman TR, Di Carlo D, Shin D, Zanos S, Chavan SS, Herzog RI, Puleo C. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nature Biomedical Engineering 2022, 6: 683-705. PMID: 35361935, DOI: 10.1038/s41551-022-00870-w.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Diabetes Mellitus - Type 1 | Metabolic Changes Induced by a Very Low Carbohydrate Diet in Youth With Type 1 Diabetes |
| Diseases of the Digestive System - Liver; Obesity & Weight Control | Effects of Hepatic Ultrasound on Metabolic Homeostasis |
| Diabetes Mellitus - Type 1; Diabetes Mellitus - Type 2; Diseases of the Endocrine System | Restoring brain metabolism and function in older adult T1DM patients using an AP system |
| Diabetes Mellitus - Type 1; Diseases of the Endocrine System; Diseases of the Nervous System | Impact of Hypoglycemia on Brain Ketone and Neurotransmitter Metabolism in Type 1 DM |
| Children's Health; Diabetes Mellitus - Type 2; Diseases of the Cardiovascular System; Diseases of the Endocrine System; Genetics - Pediatric; Obesity & Weight Control | Prevalence of Carbohydrate Intolerance in Lean and Obese Children |