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Carol L. Miller-Graziano, Ph.D.

Contact Information

Phone Numbers

Appointment: (585) 276-3000

Biography

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.

Professional Background

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

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.

Credentials

Faculty Appointments

Education

1966
BS | San Diego State Univ
Zoology

1969
MS | University of Utah
Zoology

1972
PhD | Univ of Utah Coll Medicine
Microbiology, All Other

Awards

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

Publications

Journal Articles

10/17/2006
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; .

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.

Books & Chapters

2005
Chapter Title: HSP-27 As an Anti-Inflammatory Protein
Book Title: Molecular Chaperones and Cell Signalling
Author List: Laudanski K, De A, Miller-Graziano C
Edited By: B.Henderson, G.Pockley
Published By: Cambridge Univ Press2005 in New York, NY

2000
Chapter Title: Trauma Mediators Favor Differentiation of Monocytes to Macrophage Rather Than to Dendritic Cells
Book Title: Update in Intensive Care and Emergency Medicine
Author List: Miller-Graziano, C.L.; De, A.K.; Kodys, K.
Edited By: J.C.Marshall, J.Cohen
Published By: Springer-Verlag2000 in Berlin, Germany

1996
Chapter Title: Relationship of Post-Trauma Altered IL-12 and IL-10 to Depressed Patient Mitogen Responses
Book Title: The Immune Consequences of Trauma, Shock & Sepsis - Mechanisms & Therapeutic App
Author List: De, A.K.; Kodys, K.; Fairfield, S.; Miller-Graziano, C.
Edited By: E.Faist
Published By: Springer-Verlag1996 in Berlin, Germany

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