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Carol Miller-Graziano

TitleProfessor Emeritus
InstitutionSchool of Medicine and Dentistry
DepartmentSurgery
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box SURG
Rochester NY 14642
 
 Awards And Honors
2000     Star Award for Excellence in Graduate School Teaching University of Massachusetts
 
 Overview
Dr. Miller-Graziano's laboratory has 3 NIH supported projects to assess different aspects of immunopathology in burn and trauma patients. A dysfunction in patient monocyte (MO) to dendritic (DC) cell differentiation has been identified along with a decrease in the immune stimulatory capacity of patients' MO. The current MO experiments focus on the tolerogenic capacity of patients' DC in mediating their immunodepression. Microarray analysis of DC derived from patients' dysfunctional, patients' immunostimulatory, controls' immunostimulatory and in vitro induced controls' tolerogenic populations is under way. Altered signaling proteins and receptor expression in these 2 patient and 2 control DC populations is being characterized by multicolor flow cytometry, Luminex, and RealTime PCR technology. These DC experiments particularly emphasize increases in co-inhibitory receptors like PD-L1+2, ILT3+4, and HEMV concomitant to decreases in costimulatory receptors like CD40, CD86, and CD80 as mechanisms behind dysfunctional MO/DC antigen presenting function in the immunodepressed patients. Autocrine inhibitory signaling by SIPR(alpha), CD47 and thrombospondin in patients' DC is also being assessed for their role in mediating MO driven decreased immune function post injury. The ability of patient DC to alter the responses of an HLA unrestricted, tetanus toxoid responsive, human T cell clone provides an additional assay for patient DC tolerogenic function.
A complimentary project investigates induction and maintenance of T cell adaptive tolerance as a contributor to post injury immunosuppression. An increased threshold of inhibitory signal transduction molecules and negative costimulation molecules appears to mediate some of the patients' T cell immunodepression. The induction of DC tolerogenic capacity by post injury apoptotic T cells and hyporesponsive T cells is also a focus of laboratory experiments. These 3 projects offer students an opportunity to apply fundamental immunologic principles and systems to the study of human immunopathology.

 
 Selected Publications
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  1. Zhou JY, Krovvidi RK, Gao Y, Gao H, Petritis BO, De AK, Miller-Graziano CL, Bankey PE, Petyuk VA, Nicora CD, Clauss TR, Moore RJ, Shi T, Brown JN, Kaushal A, Xiao W, Davis RW, Maier RV, Tompkins RG, Qian WJ, Camp DG, Smith RD. Trauma-associated human neutrophil alterations revealed by comparative proteomics profiling. Proteomics Clin Appl. 2013 Aug; 7(7-8):571-83.
    View in: PubMed
  2. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013 Feb 26; 110(9):3507-12.
    View in: PubMed
  3. Bandyopadhyay G, Bankey PE, Miller-Graziano CL. Trauma patients' elevated tumor necrosis related apoptosis inducing ligand (TRAIL) contributes to increased T cell apoptosis. Clin Immunol. 2012 Oct; 145(1):44-54.
    View in: PubMed
  4. Miller-Graziano C. What's new in Shock, June 2011? Shock. 2011 Jun; 35(6):539-41.
    View in: PubMed
  5. Banerjee S, Lin CF, Skinner KA, Schiffhauer LM, Peacock J, Hicks DG, Redmond EM, Morrow D, Huston A, Shayne M, Langstein HN, Miller-Graziano CL, Strickland J, O'Donoghue L, De AK. Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression. Cancer Res. 2011 Jan 15; 71(2):318-27.
    View in: PubMed
  6. Rajicic N, Cuschieri J, Finkelstein DM, Miller-Graziano CL, Hayden D, Moldawer LL, Moore E, O'Keefe G, Pelik K, Warren HS, Schoenfeld DA. Identification and interpretation of longitudinal gene expression changes in trauma. PLoS One. 2010; 5(12):e14380.
    View in: PubMed
  7. Kotz KT, Xiao W, Miller-Graziano C, Qian WJ, Russom A, Warner EA, Moldawer LL, De A, Bankey PE, Petritis BO, Camp DG, Rosenbach AE, Goverman J, Fagan SP, Brownstein BH, Irimia D, Xu W, Wilhelmy J, Mindrinos MN, Smith RD, Davis RW, Tompkins RG, Toner M. Clinical microfluidics for neutrophil genomics and proteomics. Nat Med. 2010 Sep; 16(9):1042-7.
    View in: PubMed
  8. Zhou B, Xu W, Herndon D, Tompkins R, Davis R, Xiao W, Wong WH. Analysis of factorial time-course microarrays with application to a clinical study of burn injury. Proc Natl Acad Sci U S A. 2010 Jun 1; 107(22):9923-8.
    View in: PubMed
  9. Bankey PE, Banerjee S, Zucchiatti A, De M, Sleem RW, Lin CF, Miller-Graziano CL, De AK. Cytokine induced expression of programmed death ligands in human neutrophils. Immunol Lett. 2010 Apr 8; 129(2):100-7.
    View in: PubMed
  10. Redmond EM, Morrow D, Kundimi S, Miller-Graziano CL, Cullen JP. Acetaldehyde stimulates monocyte adhesion in a P-selectin- and TNFalpha-dependent manner. Atherosclerosis. 2009 Jun; 204(2):372-80.
    View in: PubMed
  11. Miller-Graziano CL, De A, Laudanski K, Herrmann T, Bandyopadhyay S. HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function. Novartis Found Symp. 2008; 291:196-208; discussion 208-11, 221-4.
    View in: PubMed
  12. Laudanski K, De A, Miller-Graziano C. Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells. Eur J Immunol. 2007 Oct; 37(10):2812-24.
    View in: PubMed
  13. Bandyopadhyay G, De A, Laudanski K, Li F, Lentz C, Bankey P, Miller-Graziano C. Negative signaling contributes to T-cell anergy in trauma patients. Crit Care Med. 2007 Mar; 35(3):794-801.
    View in: PubMed
  14. Laudanski K, Miller-Graziano C, Xiao W, Mindrinos MN, Richards DR, De A, Moldawer LL, Maier RV, Bankey P, Baker HV, Brownstein BH, Cobb JP, Calvano SE, Davis RW, Tompkins RG. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci U S A. 2006 Oct 17; 103(42):15564-9.
    View in: PubMed
  15. Laudanski K, De A, Pellegrini J, Miller-Graziano C. Simultaneous aberrations in Mphi and T cell function adversely affect trauma patients' clinical outcome: a possible faulty IL-13 feedback loop. Clin Immunol. 2006 Feb-Mar; 118(2-3):332-41.
    View in: PubMed
  16. De AK, Miller-Graziano CL, Calvano SE, Laudanski K, Lowry SF, Moldawer LL, Remick DG, Rajicic N, Schoenfeld D, Tompkins RG. Selective activation of peripheral blood T cell subsets by endotoxin infusion in healthy human subjects corresponds to differential chemokine activation. J Immunol. 2005 Nov 1; 175(9):6155-62.
    View in: PubMed
  17. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF. A network-based analysis of systemic inflammation in humans. Nature. 2005 Oct 13; 437(7061):1032-7.
    View in: PubMed
  18. Cobb JP, Mindrinos MN, Miller-Graziano C, Calvano SE, Baker HV, Xiao W, Laudanski K, Brownstein BH, Elson CM, Hayden DL, Herndon DN, Lowry SF, Maier RV, Schoenfeld DA, Moldawer LL, Davis RW, Tompkins RG, Baker HV, Bankey P, Billiar T, Brownstein BH, Calvano SE, Camp D, Chaudry I, Cobb JP, Davis RW, Elson CM, Freeman B, Gamelli R, Gibran N, Harbrecht B, Hayden DL, Heagy W, Heimbach D, Herndon DN, Horton J, Hunt J, Laudanski K, Lederer J, Lowry SF, Maier RV, Mannick J, McKinley B, Miller-Graziano C, Mindrinos MN, Minei J, Moldawer LL, Moore E, Moore F, Munford R, Nathens A, O'keefe G, Purdue G, Rahme L, Remick D, Sailors M, Schoenfeld DA, Shapiro M, Silver G, Smith R, Stephanopoulos G, Stormo G, Tompkins RG, Toner M, Warren S, West M, Wolfe S, Xiao W, Young V. Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci U S A. 2005 Mar 29; 102(13):4801-6.
    View in: PubMed
  19. De AK, Roach SE, De M, Minielly RC, Laudanski K, Miller-Graziano CL, Bankey PE. Development of a simple method for rapid isolation of polymorphonuclear leukocytes from human blood. J Immunoassay Immunochem. 2005; 26(1):35-42.
    View in: PubMed
  20. Feezor RJ, Baker HV, Mindrinos M, Hayden D, Tannahill CL, Brownstein BH, Fay A, MacMillan S, Laramie J, Xiao W, Moldawer LL, Cobb JP, Laudanski K, Miller-Graziano CL, Maier RV, Schoenfeld D, Davis RW, Tompkins RG. Whole blood and leukocyte RNA isolation for gene expression analyses. Physiol Genomics. 2004 Nov 17; 19(3):247-54.
    View in: PubMed
  21. Laudanski K, De A, Brouxhon S, Kyrkanides S, Miller-Graziano C. Abnormal PGE(2) regulation of monocyte TNF-alpha levels in trauma patients parallels development of a more macrophage-like phenotype. Shock. 2004 Sep; 22(3):204-12.
    View in: PubMed
  22. Koniaris LG, Kaufman D, Zimmers TA, Wang N, Spitalnik PF, Henson L, Miller-Graziano C, Sitzmann JV. Two third-year medical student-level laboratory shock exercises without large animals. Surg Infect (Larchmt). 2004; 5(4):343-8.
    View in: PubMed
  23. De AK, Laudanski K, Miller-Graziano CL. Failure of monocytes of trauma patients to convert to immature dendritic cells is related to preferential macrophage-colony-stimulating factor-driven macrophage differentiation. J Immunol. 2003 Jun 15; 170(12):6355-62.
    View in: PubMed
  24. Sheth K, Friel J, Nolan B, Miller-Graziano C, Bankey P. Down-regulated circulating PMN function after injury despite enhanced p38 MAPK activity. Surg Infect (Larchmt). 2002; 3(2):151-7,discussion 157-8.
    View in: PubMed
  25. Sheth K, De A, Nolan B, Friel J, Duffy A, Ricciardi R, Miller-Graziano C, Bankey P. Heat shock protein 27 inhibits apoptosis in human neutrophils. J Surg Res. 2001 Jul; 99(1):129-33.
    View in: PubMed
  26. Mitra P, De A, Ethier MF, Mimori K, Kodys K, Shibuta K, Mori M, Madison JM, Miller-Graziano C, Barnard GF. Loss of chemokine SDF-1alpha-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2. Cell Signal. 2001 May; 13(5):311-9.
    View in: PubMed
  27. De AK, Kodys KM, Yeh BS, Miller-Graziano C. Exaggerated human monocyte IL-10 concomitant to minimal TNF-alpha induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus. J Immunol. 2000 Oct 1; 165(7):3951-8.
    View in: PubMed
  28. De AK, Kodys KM, Pellegrini J, Yeh B, Furse RK, Bankey P, Miller-Graziano CL. Induction of global anergy rather than inhibitory Th2 lymphokines mediates posttrauma T cell immunodepression. Clin Immunol. 2000 Jul; 96(1):52-66.
    View in: PubMed
  29. Pellegrini JD, De AK, Kodys K, Puyana JC, Furse RK, Miller-Graziano C. Relationships between T lymphocyte apoptosis and anergy following trauma. J Surg Res. 2000 Feb; 88(2):200-6.
    View in: PubMed
  30. De AK, Kodys K, Miller-Graziano C. Maximal T cell IL-13 production requires monocyte or monokine participation. Cytokine. 1998 Dec; 10(12):911-9.
    View in: PubMed
  31. Furse RK, Kodys K, Zhu D, Miller-Graziano CL. Increased monocyte TNF-alpha message stability contributes to trauma patients' increased TNF production. J Leukoc Biol. 1997 Oct; 62(4):524-34.
    View in: PubMed
  32. De AK, Kodys K, Puyana JC, Fudem G, Pellegrini J, Miller-Graziano CL. Only a subset of trauma patients with depressed mitogen responses have true T cell dysfunctions. Clin Immunol Immunopathol. 1997 Jan; 82(1):73-82.
    View in: PubMed
  33. Pellegrini JD, Puyana JC, Lapchak PH, Kodys K, Miller-Graziano CL. A membrane TNF-alpha/TNFR ratio correlates to MODS score and mortality. Shock. 1996 Dec; 6(6):389-96.
    View in: PubMed
  34. Seethalakshmi L, Bala RS, Malhotra RK, Austin-Ritchie T, Miller-Graziano C, Menon M, Luber-Narod J. 17 beta-estradiol induced prostatitis in the rat is an autoimmune disease. J Urol. 1996 Nov; 156(5):1838-42.
    View in: PubMed
  35. De AK, Kodys K, Puyana JC, Fudem G, Savoie P, Miller-Graziano CL. Elevated IL-8 production by trauma patients' monocytes is associated with elevated secretion of TNF alpha. Shock. 1995 Sep; 4(3):171-7.
    View in: PubMed
  36. Miller-Graziano CL, De AK, Kodys K. Altered IL-10 levels in trauma patients' M phi and T lymphocytes. J Clin Immunol. 1995 Mar; 15(2):93-104.
    View in: PubMed
  37. Miller-Graziano CL, Kodys K, Jhaver K. Normal M phi cell-associated TNF alpha is resistant to PGE2 as well as TGF beta downregulation. Ann N Y Acad Sci. 1994 Aug 15; 730:307-9.
    View in: PubMed
  38. Miller-Graziano CL, Kodys K, Gonzalez F, Fudem GM. Continued tumor necrosis factor receptor expression by trauma patients' monocytes (Mphi) despite TNF alpha secretion. Shock. 1994 May; 1(5):317-24.
    View in: PubMed
  39. Szabo G, Kodys K, Miller-Graziano CL. Dibutyryl-cAMP modulation of receptor expression and antigen presentation capacity in monocyte subpopulations. Int J Immunopharmacol. 1994 Feb; 16(2):151-62.
    View in: PubMed
  40. Miller-Graziano CL, Zhu D, Kodys K. Differential induction of human monocyte transforming growth factor beta 1 production and its regulation by interleukin 4. J Clin Immunol. 1994 Jan; 14(1):61-72.
    View in: PubMed
  41. Szabo G, Kodys K, Miller-Graziano CL. Elevated monocyte interleukin-6 (IL-6) production in immunosuppressed trauma patients. I. Role of Fc gamma RI cross-linking stimulation. J Clin Immunol. 1991 Nov; 11(6):326-35.
    View in: PubMed
  42. Szabo G, Kodys K, Miller-Graziano CL. Elevated monocyte interleukin-6 (IL-6) production in immunosppressed trauma patients. II. Downregulation by IL-4. J Clin Immunol. 1991 Nov; 11(6):336-44.
    View in: PubMed
  43. Miller-Graziano CL, Szabo G, Griffey K, Mehta B, Kodys K, Catalano D. Role of elevated monocyte transforming growth factor beta (TGF beta) production in posttrauma immunosuppression. J Clin Immunol. 1991 Mar; 11(2):95-102.
    View in: PubMed
  44. Miller-Graziano CL, Szabo G, Kodys K, Griffey K. Aberrations in post-trauma monocyte (MO) subpopulation: role in septic shock syndrome. J Trauma. 1990 Dec; 30(12 Suppl):S86-96.
    View in: PubMed
  45. Szabo G, Miller-Graziano CL. Induction and regulation of monocyte procoagulant activity. Transplantation. 1990 Aug; 50(2):301-9.
    View in: PubMed
  46. Szabo G, Miller-Graziano CL, Wu JY, Takayama T, Kodys K. Differential tumor necrosis factor production by human monocyte subsets. J Leukoc Biol. 1990 Mar; 47(3):206-16.
    View in: PubMed
  47. Szabo G, Miller CL, Kodys K. Antigen presentation by the CD4 positive monocyte subset. J Leukoc Biol. 1990 Feb; 47(2):111-20.
    View in: PubMed
  48. Takayama TK, Miller C, Szabo G. Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. Arch Surg. 1990 Jan; 125(1):29-35.
    View in: PubMed
  49. Zappala SM, Khauli RB, Miller-Graziano C, Takayama TK, Stoff JS, Menon M. Evaluation of monocyte procoagulant activity as a parameter for immunologic monitoring in renal transplantation. Transplant Proc. 1989 Feb; 21(1 Pt 2):1844-5.
    View in: PubMed
  50. Miller-Graziano CL, Fink M, Wu JY, Szabo G, Kodys K. Mechanisms of altered monocyte prostaglandin E2 production in severely injured patients. Arch Surg. 1988 Mar; 123(3):293-9.
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  51. Kudsk KA, Miller CL, Sheldon GF. Adrenalectomy in the guinea pig: operative and perioperative management. Lab Anim Sci. 1983 Apr; 33(2):177-80.
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  52. Miller CL, Graziano CJ, Lim RC. Human monocyte plasminogen activator production: correlation to altered M phi-T lymphocyte interaction. J Immunol. 1982 May; 128(5):2194-200.
    View in: PubMed
  53. Miller CL. Burns and the immune network. J Trauma. 1979 Nov; 19(11 Suppl):880-3.
    View in: PubMed
  54. Miller CL, Baker CC. Development of inhibitory macrophage (phi) after splenectomy. Transplant Proc. 1979 Jun; 11(2):1460.
    View in: PubMed
  55. Baker CC, Miller CL, Trunkey DD, Lim RC. Identity of mononuclear cells which compromise the resistance of trauma patients. J Surg Res. 1979 May; 26(5):478-87.
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  56. Miller CL, Graziano C, Lim RC. Alterations in monocyte function following trauma. Surg Forum. 1979; 30:43-5.
    View in: PubMed
  57. Baker CC, Miller CL, Trunkey DD. Correlation of traumatic shock with immunocompetence and sepsis. Surg Forum. 1979; 30:20-1.
    View in: PubMed
  58. Miller C, Petersen S, Sheldon GF, Carpenter G, Fuchs R, Claudy B. Effect of protein-sparing therapy on immunocompetence in normal and protein-depleted rats. Surg Forum. 1978; 29:63-5.
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  59. Miller CL, Trunkey DD. Thermal injury: defects in immune response induction. J Surg Res. 1977 Jun; 22(6):621-5.
    View in: PubMed
  60. Miller C, Sheldon GF, Claudy B, Carpenter G. Evaluation of total parenteral nutrition by in vitro measurement of immune capacity. Surg Forum. 1977; 28:81-2.
    View in: PubMed
  61. Miller CL, DeWitt CW. The effect of neonatal thymectomy on antibody responses to histocompatibility antigens in the rat. Cell Immunol. 1974 Aug; 13(2):278-87.
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  62. Miller C, DeWitt C. Rat alloantibody responses against strong and weak histocompatibility antigens. J Immunol. 1972 Nov; 109(5):919-26.
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  63. DeWitt CW, McDonald JH, Miller C. Spatial relationships of rat histocompatibility antigens. Transplant Proc. 1971 Mar; 3(1):198-201.
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