Carol L. Miller-Graziano, Ph.D.

Carol L. Miller-Graziano, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box SURG
Rochester, NY 14642

Professional Bio

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.

Research Bio

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.

Awards & Honors (Local)

Star Award for Excellence in Graduate School Teaching University of Massachusetts 2000 - 2000

Recent Journal Articles

Showing the 5 most recent journal articles. 69 available »

2006 Oct 17
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." Proceedings of the National Academy of Sciences of the United States of America.. 2006 Oct 17; 103(42):15564-9. Epub 2006 Oct 10.
2006
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.. 2006; . Link
2006
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." Clinical immunology : the official journal of the Clinical Immunology Society.. 2006 118(2-3):332-41. Epub 2005 Nov 21.
2005 Nov 1
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." The Journal of immunology : official journal of the American Association of Immunologists.. 2005 Nov 1; 175(9):6155-62.
2005 Oct 13
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. Epub 2005 Aug 31.

Current Appointments

Professor Emeritus - Department of Surgery, Research (SMD) - Primary

Education

PhD | Microbiology, All Other | Univ of Utah Coll Medicine1972
MS | Zoology | University of Utah1969
BS | Zoology | San Diego State Univ1966