Pharmacology & Physiology
BIOGRAPHICAL SKETCH
NAME: POSITION TITLE:
Vanessa H. Routh, Ph.D. Professor
INSTITUTION AND LOCATION DEGREE YEAR(S) FIELD OF STUDY
University of California at Davis, CA B.S. 1986 Physiology
University of California at Davis, CA M.S. 1989 Physiology
University of California at Davis, CA Ph.D. 1993 Physiology
A. Positions and Honors
POSITIONS/EXPERIENCE
1993-1995: Postdoctoral fellow; Uniformed Services Univ. Health Sci., Bethesda, MD
1995-1998: Postdoctoral fellow; New Jersey Medical School (UMDNJ), Newark, NJ
March 97: July 97: Visiting Scientist; Univ. of Aberdeen, Scotland
1998-2003: Assistant Professor; Depts of Pharmacology/Physiology and Neurosciences; New Jersey Medical School (UMDNJ), Newark, NJ
2003-2010: Associate Professor; Dept of Pharmacology/Physiology; New Jersey Medical School (UMDNJ), Newark, NJ
April 2007-June 2007: Visiting Scientist; Univ. Paris 7 (CNRS), Paris, France
Jersey Medical School (UMDNJ), Newark, NJ
2010-present: Professor; Depts of Pharmacology/Physiology and Neurosciences
OTHER PROFESSIONAL MEMBERSHIPS
2002-present: Yale Diabetes Endocrinology Research Center: External Member
HONORS:
1987/8/91: Achievement Rewards for College Scientists.
1989/93: Young Investigators Award Finalist; Meeting of the North American Association for the Study of Obesity (NAASO).
1992: University of California, Davis Graduate Fellowship.
1992/3:NIH NRSA Neurophysiology/Cardiology Training Grant (predoctoral)
1993: Carlson Prize in Physiology, University of California, Davis.
1996-8: NIH Individual National Research Service Award (NRSA).
1998-02: Career Development Award, American Diabetic Association.
UMDNJ Searle Scholar Program nominee.
Sigma Phi Honor Society.
Golden Key Honor Society
- Selected peer-reviewed publications (in chronological order). Do not include publications submitted or in preparation.
1. Routh, V. H., Murakami, D. M., Stern, J. S., Fuller, C. A., and B. A. Horwitz. Neuronal Activity in Hypothalamic Nuclei of Obese and Lean Zucker Rats. Int. J Obesity 14:879-891, 1990.
2. Routh, V. H., Hamilton, J. S., Stern, J. S., and B. A. Horwitz. Littersize, Adrenalectomy, and High Fat Diet Alter Hypothalamic Monoamines in Genetically Lean (Fa/Fa) Zucker Rats. J. Nutr. 123:74-84, 1993.
3. Levin, B. E., Planas, B., Routh, V. H., Hamilton, J. S., Stern, J. S., and B. A. Horwitz. Altered a1-Adrenergic Receptor Binding in Intact and Adrenalectomized Obese Zucker Rats (fa/fa). Brain Research 614:146-154, 1993.
4. Routh, V. H., Geitzen, D., Stern, J. S., and B. A. Horwitz. Hypothalamic Monoaminergic Activity in 11 Week Old Cold-Exposed Lean (Fa/Fa) and Obese (fa/fa) Female Zucker Rats. Obesity Research 2:28-37, 1994.
5. Routh, V. H., Stern, J. S., and B. A. Horwitz. Serotonergic Activity is Depressed in the Ventromedial Hypothalamic Nucleus (VMN) of the Obese (fa/fa) Zucker Rat as Early as 12 Days of Age. Am. J. Physiol. 267: R712-R719, 1994.
6. Routh, V. H., Stern, J. S. and B. A. Horwitz. Adrenalectomy Increased Serotonin Turnover in Brains of Obese Zucker Rats. Physiol. & Behav. 58(3):491-499, 1995.
7. Routh, V. H., and C. J. Helke. 'Tachykinin Receptors in the Spinal Cord' in Prog. Brain Res. vol 104, Chapter 6: Neuropeptides in the Spinal Cord, eds F. Nyberg, H.S. Sharma, and Z. Weisinfeld-Hallin; New York, Elsevier pp 93-108, 1995.
8. Routh, V. H., Stern, J. S., and B. A. Horwitz. 'Adaptations of Mammals to Overnutrition' in Handbook of Physiology, Section 4: Environmental Physiology, vol 2: Adaptations to the Environment. eds., C. Blatteis and M. Fregly; New York, Oxford Press pp 1411-1435, 1996.
9. Levin, B.E. and V.H. Routh. The Role of the Brain in Energy Balance and Obesity. Am. J. Physiol. 271(40):R491-500, 1996.
10. Routh, V. H., and C. J. Helke. A Novel Technique for Making Antibody Microprobes Using Thiol-terminal Silanes and a Heterobifunctional Crosslinker. J. Neuroscience Methods 71: 163-168, 1997.
11. Dunn-Meynell, A.A., Routh, V.H., McArdle, J.J., and B.E. Levin. Low Affinity Sulfonylurea Binding Sites Reside on Neuronal Cell Bodies in the Brain. Brain Research 745:1-9, 1997.
12. Routh, V.H., McArdle, J.J., and B.E. Levin. Phosphorylation Modulates the Activity of the ATP-Sensitive K+ Channel in the Ventromedial Hypothalamic Nucleus (VMN). Brain Research 778: 107-119, 1997.
13. Horwitz, B.A., Hamilton, J.S., Routh, V.H., Green, K. and A. Chan. Adiposity and Serum Leptin Increase in Fatty (fa/fa) BNZ Neonates Without Decreased VMH Serotonergic Activity. Am. J. Physiol. 274(37):E1009-E1017, 1998.
14. Levin, B.E., Dunn-Meynell, A.A., and Routh, V.H. Brain glucosensing and body energy balance: Role in obesity and diabetes Am. J. Physiol. 276: R1223- R1231, 1999.
15. Spanswick, D., Smith, M.A., Mirahamsi, S., Routh, V.H., and M.L.J. Ashford. Insulin activates ATP-sensitive K+ channels in hypothalamic neurones of lean, but not obese rats. Nature Neuroscience 3(8): 757-758, 2000.
16. Levin, B.E., Dunn-Meynell, A.A. and V.H. Routh. News and Views: Brain glucosensing and the KATP channel. Nature Neuroscience 4 (5):5-6, 2001.
17. Song, Z., Levin, B.E., McArdle J.J., Bakhos N. and Routh V.H. Convergence of Pre- and Postsynaptic Influences on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus (VMN) Diabetes 50:2673-2681, 2001.
18. Routh, V.H. Brain glucosensing neurons: Are they relevant? Physiol. & Behav. 76:403-413; 2002.
19. Levin, B.E., Dunn-Meynell, A.A., and V.H. Routh. CNS sensing and regulation of peripheral glucose levels. Int. Review Neurobiol. 51:219-258, 2002.
20. Dunn-Meynell, A.A., Routh, V.H., Kang, L., Gaspers, L. and B.E. Levin. Glucokinase is the likely mediator of glucosensing in central neurons. Diabetes 51: 2056- 65; 2002.
21. Routh, V.H. Glucosensing neurons in the ventromedial hypothalamic nucleus (VMN) and hypoglycemia associated autonomic failure (HAAF). Diabetes Metabolism Research & Reviews 19: 348-356; 2003.
22. Kang, L., Routh, V.H., Kuzhikandathil, E.V., Gaspers, L.D. and B.E. Levin. Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons, Diabetes, 53:549-559; 2004.
23. Routh,V.H., Song, Z. and X. Liu. The role of glucosensing neurons in the detection of hypoglycemia. Diabetes Technology and Therapeutics 6(3):413-421; 2004.
24. Wang, R., Liu, X., Hentges, ST, Dunn-Meynell, A.A., Levin, B.E., Wang, W. and V.H. Routh. The regulation of glucose-excited (GE) neurons by glucose and feeding-relevant peptides. Diabetes 53:1959-1965; 2004.
25. Levin, B.E., Routh, V.H., Kang, L., Sanders, N.M. and A.A. Dunn-Meynell. Neuronal glucosensing: What do we know after 50 years? Diabetes 53:2521-2528; 2004.
26. Song, Z. and V.H. Routh. Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Diabetes 54:15-22; 2005.
27. Wang, R., Cruciani-Guglielmacci, C., Migrenn, S., Magnan, C., Cotero, V.E., and V.H. Routh. The effects of oleic acid (OA) on distinct populations of neurons in the hypothalamic arcuate nucleus (ARC) are dependent on extracellular glucose levels. J. Neurophysiol. 95(3): 1491-1498, 2006.
28. Kang. L., Dunn-Meynell, A.A., Routh, V.H., Zhang, B.B., Gaspers, L.D.; Nagata, Y., Nishimura, T., Eiki, J, and B.E. Levin. Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes, 55(2):412-20, 2006.
29. McCrimmon, R.J., Song, Z., Cheng, H., McNay, E.C., Weikart-Yeckel, C. Fan, X., Routh, V.H. and R.S. Sherwin. Corticotrophin releasing factor (CRF) receptors within the ventromedial hypothalamus regulate hypoglycemia-induced hormonal counterregulation. J. Clin Ivest. 116 (6):1723-1730, 2006.
30. Song, Z. and V.H. Routh. Recurrent hypoglycemia decreases the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamic nucleus. Am. J. Physiol. Regul Integr Comp Physiol, 291(5):R1283-7. Epub 2006 Jun 22.
31. Migrenne, S., Cruciani-Guglielmacci, C., Kang, L., Wang, R.; Rouch, C., Lefevre, A., Ktorza, A., Routh, V.H., Levin, B.E., Magnan, C. Fatty Acid Signaling in the Hypothalamus and the Neural Control of Insulin Secretion. Diabetes 55 (Suppl 2): S139-S144, 2006.
32. Canabal, D.D., Song, Z., Potian, J., Beuve, A.V., McArdle, J.J. and V.H. Routh. Glucose, insulin and leptin signaling pathways converge on nitric oxide synthesis in glucose sensing neurons in the ventromedial hypothalamus (VMH). Am J Physiol Regul Integr Comp Physiol. 292(4):R1418-28, 2007. Epub 2006 Dec 14. PMID: 17170237
33. Fioramonti, X., Contie, S., Song, Z., Routh, V.H., Lorsignol A. and L. Penicaud. Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in NPY and POMC networks? Diabetes 56(5):1219-1227, 2007 [Epub ahead of print Jan 29, 2007]. PMID: 17261674
34.Canabal, D.D., Potian, J.G., Duran, R.G., McArdle, J.J. and V.H. Routh. Hyperglycemia impairs glucose and insulin regulation of nitric oxide (NO) production in glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH).Am J Physiol Regul Integr Comp Physiol. 293(2):R592-600; 2007 May 30; [Epub ahead of print] PMID: 17537841.
35. Murphy, B.A., Fioramonti, X., Jochnowitz, N., Fakira, K., Gagen, K., Contie, S., Lorsignol, A., Penicaud, L., Martin, W.J. and V. H. Routh. Fasting enhances the response of arcuate neuropeptide Y (NPY)-glucose-inhibited (GI) neurons to decreased extracellular glucose. Am.J. Physiol – Cell. Physiol. 296:746-756; 2009, Feb 11 [Epub ahead of print]. PMID: 19211911
36. Cotero, V.E. and V.H. Routh. Insulin blunts the response of glucose-excited (GE) neurons in the ventrolateral-ventromedial hypothalamic nucleus (VL-VMN) to decreased glucose. Am. J. Physiol. – Endocrinol. Metab. 2009, Feb 17 [Epub ahead of print]. PMID: 19223652
37. Murphy, B.A., Fakira, K.A., Song, Z., Beuve, A. and V. H. Routh. AMP-activated Protein Kinase (AMPK) and Nitric Oxide (NO) regulate the glucose sensitivity of ventromedial hypothalamic (VMH) glucose-inhibited (GI) neurons. Am. J. Physiology – Cell. Physiol. 297 (3): C750-758, 2009 [First published online July 1]..
38. Souayah, N. Potian, J.G., Garcia, C.C., Krivitskaya, N., Boone, C., Routh, V.H., and J.J. McArdle. Motor Unit Number Estimate (MUNE) as a predictor of Motor Dysfunction in an Animal Model of Type I Diabetes. Am. J. Physiol. – Endocrinol. Metab., 297 (3): E602-608, 2009 [First published online July 14].
39. Marsollier, N., Kassis, N., Mezghenna, M., Soty, M., Fioramonti, X., Lacombe, A., Joly, A., Pillot, B., Zitoun, C., Vilar, J., Mithieux, G., Gross, R., Lajoix, A., Routh, V.H., Magnan, C., and C. Cruciani-Guglielmacci. Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. PLoS. 4(8):e6649, 2009.
40. Fioramonti, X., Marsollier, N. Song, Z., Fakira, K.A., Pica-Mendez, A., Brown, S., Sanders, N.M., McCrimmon, R.J., Beuve, A., Magnan, C. and V.H. Routh. Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counter-regulation. Diabetes; 59 (2):519-28, 2010
41. Cotero, V.E., Zhang, B.B. and V. H. Routh. The response of glucose-excited (GE) neurons in the ventromedial hypothalamus (VMH) to decreased glucose is enhanced in a murine model of type 2 diabetes mellitus (T2DM). J. Neuroendocrinol. 22 (2): 65-74, 2010.
42. Fioramonti X, Song Z, Vazirani RP, Beuve A, Routh VH. Hypothalamic NO in hypoglycemia detection and counter-regulation: A two edged sword. Antioxid Redox Signal. 2010, in press.
43. Diggs-Andrews KA, Zhang X, Song Z, Daphna-Iken D, Routh VH, Fisher SJ. Brain Insulin Action Regulates Hypothalamic Glucose Sensing and the Counterregulatory Response to Hypoglycemia. Diabetes 59(9): 2271-2280, 2010.
44. Routh, V.H. Glucose Sensing Neurons in the Ventromedial Hypothalamus. Sensors 2010, 10, 9002-9025.
C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and non-federal support). Begin with the projects that are most relevant to the research proposed in this application. Briefly indicate the overall goals of the projects and your role (e.g. PI, Co-Investigator, Consultant) in the research project. Do not list award amounts or percent effort in projects.
PREVIOUS RESEARCH SUPPORT:
American Diabetes Association Career Development Award (Routh, P.I.) 7/1/98 – 6/30/02
“The ATP-sensitive K+ (K-ATP) channel in the Ventromedial Hypothalamic Nucleus: Role in Glucose Homeostasis”
NIH NIDDK RO1: DK55619-01A1 (Routh, P.I.) 2/1/00 – 11/31/05
“The Arcuate K-ATP channel in Health, Obesity and Diabetes”
NIH NIDDK RO1: DK64566-01 (Routh, P.I.) 11/01/02 – 7/31/07
“Glucosensing neurons in Euglycemia, Hypoglycemia & HAAF
NIH NIDDK RO1: DK55619-06 (Routh, P.I.) 1/1/05 – 12/31/09
“Glucosensing neurons in Health, Obesity and Diabetes”
Juvenile Diabetes Research Foundation (JDRF) Research Grant (Routh, P.I.) 2/1/07 – 1/31/10
“The role of nitric oxide in ventromedial hypothalamic glucose sensing”
NIH 3P30DK045735 (Program Project PI: Robert Sherwin, Yale) 2/01/2009-1/31/2011
Regulation of glucose sensing neurons by FKBP51.
ONGOING RESEARCH SUPPORT:
NIH NIDDK R56: DK55619-10A1(Routh, P.I.) 7/1/09 – 6/30/11
“Hormonal regulation of glucose sensing neurons in health and diabetes”
NIH NIDDK RO1: DK081538-01A1 (Routh, P.I.) 4/20/09 – 3/31/14
Hypoglycemia-induced nitric oxide in glucose sensing neurons and counterregulation
NIH R21: CA139063-01 (Routh, P.I.) 7/16/09 – 6/30/11
Role of neuropeptide Y-glucose inhibited (NPY-GI) neurons in cytokine-induced anorexia-cachexia
JDRF Award 4-2010-433 (Program Project PI: Robert Sherwin, Yale) 9/01/2010-8/31/2013
The role of sodium glucose transporters in glucose sensing