Michael Humphreys, MD

Title(s)Professor Emeritus, Medicine
SchoolSchool of Medicine
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    Collapse Biography 
    Collapse Education and Training
    University of California, San FranciscoResidency School of Medicine
    Collapse Awards and Honors
    American Heart Association1999John Alexander, MD Research Award
    1991Elected to American Clinical and Climatological Association
    Case Western Reserve University1965Alpha Omega Alpha Society
    Water and Electrolyte Homeostasis Section, American Physiological Society2019Leonard Share Award

    Collapse Overview 
    Collapse Overview
    Dr. Humphreys' primary research interest has been in sodium metabolism and the pathophysiology of edema formation and salt-sensitive hypertension. He and his colleagues identified that rodent models of sodium retention like nephrotic syndrome, liver cirrhosis, and pregnancy are characterized by resistance to the natriuretic actions of atrial natriuretic peptide (ANP), and this in turn is caused by a heightened activity of Type V phosphodiesterase (PDE), which catabolizes cGMP formed normally in renal collecting duct cells when ANP interacts with its renal receptors. Inhibition of Type V PDE restores ANP responsiveness in these models. His group has also identified a novel hormonal system involved in normal sodium metabolism in rodents. It involves a peptide hormone gamma-melanocyte stimulating hormone (g-MSH) released from the pituitary ACTH precursor proopiomelanocortin. When animals are fed a high salt diet, g-MSH synthesis and secretion are up-regulated; it acts on the kidneys to increase sodium excretion, and on the brain to dampen down sympathetic excitation which occurs with high sodium intakes. When rodents have impaired ability to increase g-MSH secretion during ingestion of the high sodium diet, or lack the melanocortinr receptor with which it interacts, marked hypertension develops, and is accompanied by insulin resistance.
    Dr. Humphreys has also done clinical research in these areas and has studied the occurrence of HIV-associated nephropathy in patients at San Francisco General Hospital. He participated in early studies measuring nitrogen balance in ESRD patients treated with hemodialysis, and was for a short time a site director for the Frequent Hemodialysis Network clinical trial.

    Collapse Research 
    Collapse Research Activities and Funding
    gamma-MSH and Sodium Metabolism
    NIH/NHLBI R01HL068871Apr 1, 2003 - Mar 31, 2009
    Role: Principal Investigator
    NIH/NIDDK R01DK058812Mar 1, 2001 - Jan 31, 2006
    Role: Principal Investigator
    NIH/NIDDK R01DK031623Mar 1, 1983 - Nov 30, 1993
    Role: Principal Investigator
    NIH/NIADDK R01AM031623Mar 1, 1983 - Feb 28, 1986
    Role: Principal Investigator
    General Clinical Research Center
    NIH/NCRR M01RR000083Oct 1, 1974 - Nov 30, 2007
    Role: Co-Investigator

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    Collapse Faculty Mentoring

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Humphreys MH. Renal nerves and CKD: is renal denervation the answer? J Am Soc Nephrol. 2012 Jul; 23(7):1132-5. PMID: 22677558.
      View in: PubMed
    2. Humphreys MH. The brain splits obesity and hypertension. Nat Med. 2011 Jul 07; 17(7):782-3. PMID: 21738154.
      View in: PubMed
    3. Humphreys MH, Ni XP, Pearce D. Cardiovascular effects of melanocortins. Eur J Pharmacol. 2011 Jun 11; 660(1):43-52. PMID: 21199648; PMCID: PMC3086937.
    4. Sasser JM, Ni XP, Humphreys MH, Baylis C. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat. Am J Physiol Renal Physiol. 2010 Oct; 299(4):F810-4. PMID: 20668100; PMCID: PMC2957261.
    5. Chen S, Grigsby CL, Law CS, Ni X, Nekrep N, Olsen K, Humphreys MH, Gardner DG. Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents. J Clin Invest. 2009 Jun; 119(6):1647-58. PMID: 19436108; PMCID: PMC2689130.
    6. Ni XP, van Dijk C, Pearce D, Humphreys MH. Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone. Exp Physiol. 2009 Aug; 94(8):867-76. PMID: 19429645; PMCID: PMC2853237.
    7. Ni XP, Humphreys MH. Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet. Am J Hypertens. 2008 Dec; 21(12):1284-7. PMID: 18802429; PMCID: PMC3035849.
    8. Ni XP, Humphreys MH. Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat. Am J Hypertens. 2007 Aug; 20(8):862-5. PMID: 17679034.
      View in: PubMed
    9. Humphreys MH. Cardiovascular and renal actions of melanocyte-stimulating hormone peptides. Curr Opin Nephrol Hypertens. 2007 Jan; 16(1):32-8. PMID: 17143069.
      View in: PubMed
    10. Ni XP, Butler AA, Cone RD, Humphreys MH. Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J Hypertens. 2006 Nov; 24(11):2239-46. PMID: 17053546.
      View in: PubMed
    11. Knight S, Snellen H, Humphreys M, Baylis C. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat. Am J Physiol Renal Physiol. 2007 Feb; 292(2):F655-9. PMID: 17003222; PMCID: PMC2765210.
    12. Ni XP, Bhargava A, Pearce D, Humphreys MH. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Am J Physiol Regul Integr Comp Physiol. 2006 Mar; 290(3):R560-7. PMID: 16195498.
      View in: PubMed
    13. Chen S, Ni XP, Humphreys MH, Gardner DG. 1,25 dihydroxyvitamin d amplifies type a natriuretic peptide receptor expression and activity in target cells. J Am Soc Nephrol. 2005 Feb; 16(2):329-39. PMID: 15590756.
      View in: PubMed
    14. Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr. 2004 Aug; 80(2):299-307. PMID: 15277149.
      View in: PubMed
    15. Ni XP, Safai M, Rishi R, Baylis C, Humphreys MH. Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat. J Am Soc Nephrol. 2004 May; 15(5):1254-60. PMID: 15100365; PMCID: PMC2756797.
    16. Kalantar-Zadeh K, Kopple JD, Humphreys MH, Block G. Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients. Nephrol Dial Transplant. 2004 Jun; 19(6):1507-19. PMID: 15069177.
      View in: PubMed
    17. Humphreys MH. Gamma-MSH, sodium metabolism, and salt-sensitive hypertension. Am J Physiol Regul Integr Comp Physiol. 2004 Mar; 286(3):R417-30. PMID: 14761863.
      View in: PubMed
    18. Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD. A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients. J Am Soc Nephrol. 2004 Feb; 15(2):442-53. PMID: 14747392.
      View in: PubMed
    19. Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant. 2004 Jan; 19(1):141-9. PMID: 14671049.
      View in: PubMed
    20. Mayan H, Ni XP, Almog S, Humphreys MH. Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat. Hypertension. 2003 Nov; 42(5):962-7. PMID: 14568996.
      View in: PubMed
    21. Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest. 2003 Apr; 111(8):1251-8. PMID: 12697744; PMCID: PMC152936.
    22. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003 Mar; 63(3):793-808. PMID: 12631061.
      View in: PubMed
    23. Chen S, Cao L, Intengan HD, Humphreys M, Gardner DG. Osmoregulation of endothelial nitric-oxide synthase gene expression in inner medullary collecting duct cells. Role in activation of the type A natriuretic peptide receptor. J Biol Chem. 2002 Sep 06; 277(36):32498-504. PMID: 12082097.
      View in: PubMed