Raimund Herzog, MD, MHS
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
- Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swineCotero 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.
- Glutamate–Serine–Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver DiseaseLeonetti 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 2020, 7: 270. PMID: 33291552, PMCID: PMC7761842, DOI: 10.3390/children7120270.
- O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growthSingh 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 2019, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.
- Mitochondrial MsrB2 serves as a switch and transducer for mitophagyLee SH, Lee S, Du J, Jain K, Ding M, Kadado AJ, Atteya G, Jaji Z, Tyagi T, Kim W, 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.
- 7-LB: Dichloroacetate Improves Cognitive Function during Hypoglycemia in T1DM PatientsGROSKREUTZ D, TRICO D, TAI N, BELFORT-DEAGUIAR R, LEVENTHAL J, LAM W, KNIGHT M, GANNON J, HERZOG R. 7-LB: Dichloroacetate Improves Cognitive Function during Hypoglycemia in T1DM Patients Diabetes 2019, 68 DOI: 10.2337/db19-7-lb.
- Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylationWang 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.
- Nanopatterned Bulk Metallic Glass BiosensorsKinser ER, Padmanabhan J, Yu R, Corona SL, Li J, Vaddiraju S, Legassey A, Loye A, Balestrini J, Solly DA, Schroers J, Taylor A, Papadimitrakopoulos F, Herzog RI, Kyriakides TR. Nanopatterned Bulk Metallic Glass Biosensors ACS Sensors 2017, 2: 1779-1787. PMID: 29115132, DOI: 10.1021/acssensors.7b00455.
- Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortexFeyter H, Herzog RI, Steensma BR, Klomp DWJ, Brown PB, Mason GF, Rothman DL, Graaf R. Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex Magnetic Resonance In Medicine 2017, 80: 11-20. PMID: 29134686, PMCID: PMC5876108, DOI: 10.1002/mrm.27003.
- Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary FibrosisRyu 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.
- A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver DiseaseGoffredo 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: 642. PMID: 28640216, PMCID: PMC5537762, DOI: 10.3390/nu9070642.
- Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in AdolescentsTricò 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 & Metabolism 2017, 102: 2473-2481. PMID: 28482070, PMCID: PMC5505187, DOI: 10.1210/jc.2017-00475.
- β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flaresGoldberg E, Asher J, Molony R, Shaw A, Zeiss C, Wang C, Morozova-Roche L, Herzog R, Iwasaki A, Dixit V. β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares The Journal Of Immunology 2017, 198: 206.18-206.18. DOI: 10.4049/jimmunol.198.supp.206.18.
- Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?Tricò 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 And Redox Signaling 2017, 30: 241-250. PMID: 28279074, PMCID: PMC6277079, DOI: 10.1089/ars.2017.7049.
- Metabolic brain adaptations to recurrent hypoglycaemia may explain the link between type 1 diabetes mellitus and epilepsy and point towards future study and treatment optionsTricò 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.
- β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout FlaresGoldberg 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.
- Pigment epithelium‐derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockadeBelinsky 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 The FASEB Journal 2016, 30: 2837-2848. PMID: 27127101, PMCID: PMC4970601, DOI: 10.1096/fj.201500027r.
- Quantification of 1H NMR spectra from human plasmade Graaf RA, Prinsen H, Giannini C, Caprio S, Herzog RI. Quantification of 1H NMR spectra from human plasma Metabolomics 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 factorXiang 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: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.
- Vaccination with Single Chain Antigen Receptors for Islet-Derived Peptides Presented on I-Ag7 Delays Diabetes in NOD Mice by Inducing Anergy in Self-Reactive T-CellsGurr W, Shaw M, Herzog RI, Li Y, Sherwin R. Vaccination with Single Chain Antigen Receptors for Islet-Derived Peptides Presented on I-Ag7 Delays Diabetes in NOD Mice by Inducing Anergy in Self-Reactive T-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 hypoglycemiaHerzog 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 Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.
- Can tight glycemic control in diabetes benefit cognition?Herzog RI, Sherwin RS. Can tight glycemic control in diabetes benefit cognition? Nature Reviews Neurology 2012, 8: 124-126. 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 ResonanceHerzog 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: 1856-1858. PMID: 21709281, PMCID: PMC3121425, DOI: 10.2337/db11-0498.
- Recurrent Antecedent Hypoglycemia Alters Neuronal Oxidative Metabolism In VivoJiang 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: 1266-1274. PMID: 19276443, PMCID: PMC2682668, DOI: 10.2337/db08-1664.
- Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent HypoglycemiaChan 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 Reponses After Antecedent Hypoglycemia Diabetes 2008, 57: 1363-1370. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.
- 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.
- Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residueLeffler 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: 454-463. PMID: 15981012, DOI: 10.1007/s00424-005-1463-x.
- Nav1.6 channels generate resurgent sodium currents in spinal sensory neuronsCummins TR, Dib-Hajj SD, Herzog RI, Waxman SG. Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons FEBS Letters 2005, 579: 2166-2170. PMID: 15811336, DOI: 10.1016/j.febslet.2005.03.009.
- Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional PropertiesHerzog 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 Journal Of Neuroscience 2003, 23: 8261-8270. PMID: 12967988, PMCID: PMC6740705, DOI: 10.1523/jneurosci.23-23-08261.2003.
- Distinct repriming and closed‐state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neuronsHerzog R, Cummins T, Ghassemi F, Dib‐Hajj S, Waxman S. 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: 741-750. DOI: 10.1111/j.1469-7793.2003.00741.x.
- Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neuronsHerzog 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: 741-750. PMID: 12843211, PMCID: PMC2343279, DOI: 10.1113/jphysiol.2003.047357.
- The pentapeptide QYNAD does not block voltage-gated sodium channelsBrinkmeier H, Weber F, Aulkemeyer P, Wollinsky K, Rudel R, Cummins T, Renganathan M, Herzog R, Dib-Hajj S, Waxman S, Stys P, Horn R. The pentapeptide QYNAD does not block voltage-gated sodium channels Neurology 2003, 60: 1871-1872. PMID: 12796562, DOI: 10.1212/wnl.60.11.1871-a.
- The pentapeptide QYNAD does not block voltage-gated sodium channelsCummins 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: 224-229. PMID: 12552035, DOI: 10.1212/01.wnl.0000042423.36650.bd.
- Persistent TTX-Resistant Na+ Current Affects Resting Potential and Response to Depolarization in Simulated Spinal Sensory NeuronsHerzog 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: 1351-1364. PMID: 11535682, DOI: 10.1152/jn.2001.86.3.1351.
- 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 NeuronsCummins 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 Journal Of Neuroscience 2001, 21: 5952-5961. PMID: 11487618, PMCID: PMC6763143, DOI: 10.1523/jneurosci.21-16-05952.2001.
Clinical Trials
Conditions | Study Title |
---|---|
Diabetes Mellitus - Type 2 | Type 2 Diabetes Ultrasound Study |
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; 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 |