Matt Luther MD

Department: Medicine

Biography

I am a physician scientist with clinical training in internal medicine, nephrology and hypertension. I am clinically active in the Vanderbilt Hypertension clinic, which focuses on evaluation and treatment of resistant and secondary forms of hypertension.

The goal of my translational research program is to discover mechanisms of hypertension and complications, through studies in animals and humans. My specialized research expertise includes clinical study design related to metabolism (insulin resistance and secretion) and hypertension.

Research in the Luther lab is multidisciplinary crossing the fields of pharmacology, endocrinology, nephrology, and biochemistry. We have developed collaborations with investigators with a common interest in translational research to apply state-of-the-art technology to advance our clinical studies.

We have demonstrated that aldosterone, a hormone which regulates blood pressure, produces inflammation and impairs insulin secretion in humans. Using a proteomic approach, we have has also identified novel biomarkers of kidney sodium channel activation in humans. Additionally, we have demonstrated that the arachidonic acid CYP450 metabolite epoxyeicosatrienoic acid is associated with insulin sensitivity in mice and in humans.

Featured Publications

1. Early urine electrolyte patterns in patients with acute heart failure.

Collins SP, Jenkins CA, Baughman A, Miller KF, Storrow AB, Han JH, Brown NJ, Liu D, Luther JM, McNaughton CD, Self WH, Peng D, Testani JM, Lindenfeld J (2019) ESC Heart Fail 6(1): 80-88

Citation ⋅ 30295437 (PubMed) PMC6351901 (PubMed Central)

2. Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

Chaugai S, Dickson AL, Shuey MM, Feng Q, Barker KA, Wei WQ, Luther JM, Stein CM, Chung CP (2019) Clin Pharmacol Ther 105(3): 703-709

Citation ⋅ 30223305 (PubMed) PMC6379114 (PubMed Central)

3. The Cytochrome P450 Slow Metabolizers CYP2C92 and CYP2C93 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.

Sausville LN, Gangadhariah MH, Chiusa M, Mei S, Wei S, Zent R, Luther JM, Shuey MM, Capdevila JH, Falck JR, Guengerich FP, Williams SM, Pozzi A (2018) Cancer Res 78(17): 4865-4877

Citation ⋅ 30012669 (PubMed) PMC6125168 (PubMed Central)

See all publications

Publications

1. Early urine electrolyte patterns in patients with acute heart failure.

Collins SP, Jenkins CA, Baughman A, Miller KF, Storrow AB, Han JH, Brown NJ, Liu D, Luther JM, McNaughton CD, Self WH, Peng D, Testani JM, Lindenfeld J (2019) ESC Heart Fail 6(1): 80-88

Citation ⋅ 30295437 (PubMed) PMC6351901 (PubMed Central)

2. Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

Chaugai S, Dickson AL, Shuey MM, Feng Q, Barker KA, Wei WQ, Luther JM, Stein CM, Chung CP (2019) Clin Pharmacol Ther 105(3): 703-709

Citation ⋅ 30223305 (PubMed) PMC6379114 (PubMed Central)

3. The Cytochrome P450 Slow Metabolizers CYP2C92 and CYP2C93 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.

Sausville LN, Gangadhariah MH, Chiusa M, Mei S, Wei S, Zent R, Luther JM, Shuey MM, Capdevila JH, Falck JR, Guengerich FP, Williams SM, Pozzi A (2018) Cancer Res 78(17): 4865-4877

Citation ⋅ 30012669 (PubMed) PMC6125168 (PubMed Central)

4. Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans.

Gangadhariah MH, Dieckmann BW, Lantier L, Kang L, Wasserman DH, Chiusa M, Caskey CF, Dickerson J, Luo P, Gamboa JL, Capdevila JH, Imig JD, Yu C, Pozzi A, Luther JM (2017) Diabetologia 60(6): 1066-1075

Citation ⋅ 28352940 (PubMed) PMC5921930 (PubMed Central)

5. Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency.

Arnold AC, Garland EM, Celedonio JE, Raj SR, Abumrad NN, Biaggioni I, Robertson D, Luther JM, Shibao CA (2017) J Clin Endocrinol Metab 102(1): 10-14

Citation ⋅ 27778639 (PubMed) PMC5413093 (PubMed Central)

6. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men.

Luther JM, Brown NJ (2016) Prostaglandins Other Lipid Mediat 125(): 2-7

Citation ⋅ 27448715 (PubMed) PMC5035218 (PubMed Central)

7. Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

Shah SS, Ramirez CE, Powers AC, Yu C, Shibao CA, Luther JM (2016) Metabolism 65(6): 835-42

Citation ⋅ 27173462 (PubMed) PMC4867079 (PubMed Central)

8. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.

Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA (2015) J Clin Endocrinol Metab 100(12): 4533-40

Citation ⋅ 26580240 (PubMed) PMC4667163 (PubMed Central)

9. Aldosterone in vascular and metabolic dysfunction.

Luther JM (2016) Curr Opin Nephrol Hypertens 25(1): 16-21

Citation ⋅ 26575396 (PubMed) PMC4824306 (PubMed Central)

10. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

Qi Y, Wang X, Rose KL, MacDonald WH, Zhang B, Schey KL, Luther JM (2016) J Am Soc Nephrol 27(2): 646-56

Citation ⋅ 26113616 (PubMed) PMC4731116 (PubMed Central)

11. Proteomics characterization of exosome cargo.

Schey KL, Luther JM, Rose KL (2015) Methods 87(): 75-82

Citation ⋅ 25837312 (PubMed) PMC4591097 (PubMed Central)

12. Effects of aldosterone on insulin sensitivity and secretion.

Luther JM (2014) Steroids 91(): 54-60

Citation ⋅ 25194457 (PubMed) PMC4252580 (PubMed Central)

13. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans.

Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ (2014) Prostaglandins Other Lipid Mediat 113-115(): 38-44

Citation ⋅ 25173047 (PubMed) PMC4253976 (PubMed Central)

14. Hypertension is a major contributor to 20-hydroxyeicosatetraenoic acid-mediated kidney injury in diabetic nephropathy.

Gangadhariah MH, Luther JM, Garcia V, Paueksakon P, Zhang MZ, Hayward SW, Love HD, Falck JR, Manthati VL, Imig JD, Schwartzman ML, Zent R, Capdevila JH, Pozzi A (2015) J Am Soc Nephrol 26(3): 597-610

Citation ⋅ 25071086 (PubMed) PMC4341468 (PubMed Central)

15. Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans.

Luther JM, Byrne LM, Yu C, Wang TJ, Brown NJ (2014) J Clin Endocrinol Metab 99(10): E1895-902

Citation ⋅ 25029426 (PubMed) PMC4184066 (PubMed Central)

16. Is there a new dawn for selective mineralocorticoid receptor antagonism?

Luther JM (2014) Curr Opin Nephrol Hypertens 23(5): 456-61

Citation ⋅ 24992570 (PubMed) PMC4248353 (PubMed Central)

17. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.

Brown JM, Williams JS, Luther JM, Garg R, Garza AE, Pojoga LH, Ruan DT, Williams GH, Adler GK, Vaidya A (2014) Hypertension 63(2): 273-80

Citation ⋅ 24191286 (PubMed) PMC3898197 (PubMed Central)

18. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.

Gilbert K, Nian H, Yu C, Luther JM, Brown NJ (2013) J Hypertens 31(4): 820-9

Citation ⋅ 23385647 (PubMed) PMC3800119 (PubMed Central)

19. Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice.

Luo P, Dematteo A, Wang Z, Zhu L, Wang A, Kim HS, Pozzi A, Stafford JM, Luther JM (2013) Diabetologia 56(4): 901-10

Citation ⋅ 23314847 (PubMed) PMC3593801 (PubMed Central)

20. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury.

Luther JM, Luo P, Wang Z, Cohen SE, Kim HS, Fogo AB, Brown NJ (2012) Kidney Int 82(6): 643-51

Citation ⋅ 22622494 (PubMed) PMC3434275 (PubMed Central)

21. Patient knowledge of blood pressure target is associated with improved blood pressure control in chronic kidney disease.

Wright-Nunes JA, Luther JM, Ikizler TA, Cavanaugh KL (2012) Patient Educ Couns 88(2): 184-8

Citation ⋅ 22459637 (PubMed) PMC3404190 (PubMed Central)

22. Sodium intake, ACE inhibition, and progression to ESRD.

Luther JM (2012) J Am Soc Nephrol 23(1): 10-2

Citation ⋅ 22173698 (PubMed)

23. Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis.

Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ (2012) J Am Soc Nephrol 23(2): 334-42

Citation ⋅ 22158433 (PubMed) PMC3269170 (PubMed Central)

24. Proteomic analysis of urine exosomes by multidimensional protein identification technology (MudPIT).

Wang Z, Hill S, Luther JM, Hachey DL, Schey KL (2012) Proteomics 12(2): 329-38

Citation ⋅ 22106071 (PubMed) PMC3517144 (PubMed Central)

25. The renin-angiotensin-aldosterone system and glucose homeostasis.

Luther JM, Brown NJ (2011) Trends Pharmacol Sci 32(12): 734-9

Citation ⋅ 21880378 (PubMed) PMC3223326 (PubMed Central)

26. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans.

Chamarthi B, Williams GH, Ricchiuti V, Srikumar N, Hopkins PN, Luther JM, Jeunemaitre X, Thomas A (2011) Am J Hypertens 24(10): 1143-8

Citation ⋅ 21716327 (PubMed) PMC3807212 (PubMed Central)

27. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets.

Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ (2011) Diabetologia 54(8): 2152-63

Citation ⋅ 21519965 (PubMed) PMC3216479 (PubMed Central)

28. Aldosterone postnatally, but not at birth, is required for optimal induction of renal mineralocorticoid receptor expression and sodium reabsorption.

Martinerie L, Viengchareun S, Meduri G, Kim HS, Luther JM, Lombès M (2011) Endocrinology 152(6): 2483-91

Citation ⋅ 21467193 (PubMed) PMC3100620 (PubMed Central)

29. Protein profile of exosomes from trabecular meshwork cells.

Stamer WD, Hoffman EA, Luther JM, Hachey DL, Schey KL (2011) J Proteomics 74(6): 796-804

Citation ⋅ 21362503 (PubMed) PMC3085584 (PubMed Central)

30. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function.

Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW (2010) Antimicrob Agents Chemother 54(3): 1146-51

Citation ⋅ 20038622 (PubMed) PMC2825963 (PubMed Central)

31. Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis.

Marney AM, Ma J, Luther JM, Ikizler TA, Brown NJ (2009) J Am Soc Nephrol 20(10): 2246-52

Citation ⋅ 19628666 (PubMed) PMC2754101 (PubMed Central)

32. 'Labile hypertension' can be due to autonomic nervous system failure.

Raj SR, Luther JM, Sato K, Diedrich A (2009) Kidney Int 75(8): 860; author reply 860-1

Citation ⋅ 19337219 (PubMed)

33. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt.

Lea WB, Kwak ES, Luther JM, Fowler SM, Wang Z, Ma J, Fogo AB, Brown NJ (2009) Kidney Int 75(9): 936-44

Citation ⋅ 19225557 (PubMed) PMC2770712 (PubMed Central)

34. Endogenous aldosterone contributes to acute angiotensin II-stimulated plasminogen activator inhibitor-1 and preproendothelin-1 expression in heart but not aorta.

Luther JM, Wang Z, Ma J, Makhanova N, Kim HS, Brown NJ (2009) Endocrinology 150(5): 2229-36

Citation ⋅ 19106220 (PubMed) PMC2671907 (PubMed Central)

35. Blood pressure targets in hemodialysis patients.

Luther JM, Golper TA (2008) Kidney Int 73(6): 667-8

Citation ⋅ 18309346 (PubMed)

36. 17Beta-estradiol increases basal but not bradykinin-stimulated release of active t-PA in young postmenopausal women.

Pretorius M, van Guilder GP, Guzman RJ, Luther JM, Brown NJ (2008) Hypertension 51(4): 1190-6

Citation ⋅ 18259028 (PubMed) PMC2673569 (PubMed Central)

37. Bradykinin type 2 receptor BE1 genotype influences bradykinin-dependent vasodilation during angiotensin-converting enzyme inhibition.

Van Guilder GP, Pretorius M, Luther JM, Byrd JB, Hill K, Gainer JV, Brown NJ (2008) Hypertension 51(2): 454-9

Citation ⋅ 18180402 (PubMed) PMC2581632 (PubMed Central)

38. The bradykinin type 2 receptor BE1 polymorphism and ethnicity influence systolic blood pressure and vascular resistance.

Pretorius MM, Gainer JV, Van Guilder GP, Coelho EB, Luther JM, Fong P, Rosenbaum DD, Malave HA, Yu C, Ritchie MD, Vaughan DE, Brown NJ (2008) Clin Pharmacol Ther 83(1): 122-9

Citation ⋅ 17522594 (PubMed)

39. Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism.

Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, Brown NJ (2006) Hypertension 48(6): 1050-7

Citation ⋅ 17043157 (PubMed)

40. Bradykinin and its metabolite bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans.

Murphey LJ, Malave HA, Petro J, Biaggioni I, Byrne DW, Vaughan DE, Luther JM, Pretorius M, Brown NJ (2006) J Pharmacol Exp Ther 318(3): 1287-92

Citation ⋅ 16772538 (PubMed)

41. Angiotensin-converting enzyme inhibition increases basal vascular tissue plasminogen activator release in women but not in men.

Pretorius M, Luther JM, Murphey LJ, Vaughan DE, Brown NJ (2005) Arterioscler Thromb Vasc Biol 25(11): 2435-40

Citation ⋅ 16166566 (PubMed)

42. Utility of bone marrow biopsy for rapid diagnosis of febrile illnesses in patients with human immunodeficiency virus infection.

Luther JM, Lakey DL, Larson RS, Kallianpur AR, D'Agata E, Cousar JB, Haas DW (2000) South Med J 93(7): 692-7

Citation ⋅ 10923958 (PubMed)

43. Preservation of function and histologic appearance in the injured glottis with topical mitomycin-C.

Spector JE, Werkhaven JA, Spector NC, Huang S, Page RN, Baranowski B, Luther M, McGehee B, Reinisch L (1999) Laryngoscope 109(7 Pt 1): 1125-9

Citation ⋅ 10401854 (PubMed)

VCKD Members

Matt Luther, MD

Dr.

Contact Information

Matt Luther MD

Biography

Featured Publications

1. Early urine electrolyte patterns in patients with acute heart failure.

2. Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

3. The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.

Publications

1. Early urine electrolyte patterns in patients with acute heart failure.

2. Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

3. The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.

4. Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans.

5. Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency.

6. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men.

7. Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

8. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.

9. Aldosterone in vascular and metabolic dysfunction.

10. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

11. Proteomics characterization of exosome cargo.

12. Effects of aldosterone on insulin sensitivity and secretion.

13. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans.

14. Hypertension is a major contributor to 20-hydroxyeicosatetraenoic acid-mediated kidney injury in diabetic nephropathy.

15. Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans.

16. Is there a new dawn for selective mineralocorticoid receptor antagonism?

17. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.

18. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.

19. Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice.

20. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury.

21. Patient knowledge of blood pressure target is associated with improved blood pressure control in chronic kidney disease.

22. Sodium intake, ACE inhibition, and progression to ESRD.

23. Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis.

24. Proteomic analysis of urine exosomes by multidimensional protein identification technology (MudPIT).

25. The renin-angiotensin-aldosterone system and glucose homeostasis.

26. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans.

27. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets.

28. Aldosterone postnatally, but not at birth, is required for optimal induction of renal mineralocorticoid receptor expression and sodium reabsorption.

29. Protein profile of exosomes from trabecular meshwork cells.

30. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function.

31. Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis.

32. 'Labile hypertension' can be due to autonomic nervous system failure.

33. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt.

34. Endogenous aldosterone contributes to acute angiotensin II-stimulated plasminogen activator inhibitor-1 and preproendothelin-1 expression in heart but not aorta.

35. Blood pressure targets in hemodialysis patients.

36. 17Beta-estradiol increases basal but not bradykinin-stimulated release of active t-PA in young postmenopausal women.

37. Bradykinin type 2 receptor BE1 genotype influences bradykinin-dependent vasodilation during angiotensin-converting enzyme inhibition.

38. The bradykinin type 2 receptor BE1 polymorphism and ethnicity influence systolic blood pressure and vascular resistance.

39. Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism.

40. Bradykinin and its metabolite bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans.

41. Angiotensin-converting enzyme inhibition increases basal vascular tissue plasminogen activator release in women but not in men.

42. Utility of bone marrow biopsy for rapid diagnosis of febrile illnesses in patients with human immunodeficiency virus infection.

43. Preservation of function and histologic appearance in the injured glottis with topical mitomycin-C.

3. The Cytochrome P450 Slow Metabolizers CYP2C92 and CYP2C93 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.

3. The Cytochrome P450 Slow Metabolizers CYP2C92 and CYP2C93 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production.