2010 Clinical Awardees
The 2010 award recipients are listed below with a short description of their project(s).
Awardee: Alessandra Franco, MD
Assistant Professor, Department of Pediatrics
Characterization of activated, memory and regulatory T-cells in Kawasaki disease
Abstract: Significance of the Research: Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease in developed countries, which if left untreated, results in serious coronary artery damage in 25% of patients. Autopsy studies in children who die during the acute phase of KD demonstrate infiltration of T-cells, particularly CD8+ cytotoxic T-cells, into the coronary artery wall. This suggests that T-cell activation and infiltration into selected compartments are critically involved in the pathogenesis of KD. Our recent study on the number and function of effector memory T-cells (Tem) (funded by R21 HL091494) suggested that these cells secrete pro-inflammatory lymphokines and are likely to be mediators of tissue destruction in the arterial wall (Autoimmunity, in press).
We also found that approximately 40% of circulating T-cells in acute KD subjects have a phenotype consistent with peripherally-induced regulatory T-cells (Tregs). This suggests that Tregs may be responsible for the self-limited nature of KD. This proposal seeks to monitor T cell activation, development of T cell memory and immune-regulation in acute, sub-acute and convalescent KD subjects who are currently enrolling in a clinical trial of 2 different therapies. These studies add significant scientific value to the on-going clinical trial and may lead to new biomarkers and treatments. We previously showed that the size (and persistence) of pro-inflammatory T cells in the effector memory compartment during the sub-acute phase of KD correlates with unfavorable genetic associations, while the large expansion of Treg during the acute phase correlates with a favorable prognosis and is responsible for the self-limited nature of the disease.
Specific aim and summary of methods: Characterization of acute, effector and central memory, and regulatory T-cells in acute, sub-acute and convalescent KD subjects
KD subjects will be obtained from an ongoing double-blind, randomized, placebocontrolled clinical trial evaluating the addition of infliximab to primary therapy with IVIG. Peripheral blood mononuclear cells from 10 sequential KD subjects will be separated by Ficoll Hypaque at three time points: pre-treatment, 2 weeks post-treatment and 1-3 months after treatment to be stained with monoclonal antibodies (MoAbs) to characterize activated, memory and regulatory T cells, namely DR, CD4, CD8, CCR7, IL-15r, FoxP3 and CD25high.
Expected results: We expect the numbers of activated T-cells and effector memory T-cells to vary among KD patients and to possibly correlate with disease outcome (coronary artery aneurysms and response to therapy). Increased numbers of circulating effector memory CD8+ are anticipated to correlate with more severe clinical disease (higher CRP, ESR, % bands) and worse outcomes, as suggested by the predominant infiltration of CD8+ Tcells in the coronary artery wall in autopsy specimens. On the other hand, expansion of regulatory T cells is anticipated to correlate with a successful response to therapy.
The opportunity to monitor regulatory T-cells before and after treatment with IVIG or IVIG plus infliximab will provide new information on the role of immune regulation in modulating the immunopathology in KD.
Awardee: Lori Montross, PhD
The Institute for Palliative Medicine at San Diego Hospice
Associate Director, Palliative Care Psychiatry Program
The treatment satisfaction and cost of implementing Dignity Therapy in a community based hospice setting: A mixed methods assessment.
Abstract: Introduction: This study will assess the level of treatment satisfaction and cost associated with implementing Dignity Therapy in a community-based hospice setting – the San Diego Hospice and Institute for Palliative Medicine (SDHIPM). Dignity Therapy has been studied in a randomized controlled trial, but has yet to be evaluated for its applicability and cost in a “real-world” setting.
Background: Dignity therapy is an empirically-supported, individualized psychotherapy designed for adults at the end of life. Dignity Therapy is a brief treatment; performed in approximately three sessions over the course of one week, and involves the completion of a life review interview at the patient’s bedside. The interview utilizes a published 12-question protocol derived by researchers (e.g., “When did you feel most alive?”, “What do you feel most proud of?”) and is digitally recorded and transcribed, thus creating a formal “legacy” document. Once transcribed, the clinician meets with the patient to edit the document and to create a final summary as well as a title for their story. At the end of the process, a leather-bound legacy document is created for the patient, with possible dissemination to desired loved ones and family members. The creation of a lasting legacy document has been found to enhance patients’ feelings of self-worth and “dignity,” and further serves as a concrete reminder of their cherished life events.
Methods: This study gathers data from 3 primary sources: 50 patients, 50 patient-designated family members or caregivers, and 25 multidisciplinary hospice staff. The SDHIPM daily census of 900+ patients supports this enrollment goal. The outcomes include quantitative measures of the cost for treatment delivery (hours of clinician time, cost of legacy document transcripts), and changes in patients’ quality and meaning in life immediately before and after the treatment (SF-12 and FACIT-Sp measures). Treatment satisfaction results will be obtained in both a quantitative (CSQ-8) and qualitative manner. Specifically, all participants complete a semi-structured interview assessing their personal perspectives regarding the treatment’s impact, outcomes, costs and benefits. QSR NVivo software will be used to generate thematic analyses of the patient, family member, and staff perspectives.
Proposed Results: This study is specifically designed to fuel larger NIH-funded cost-effectiveness studies of Dignity Therapy in the future, and to begin translating the impact of this treatment within the community. Organizational decision makers often determine whether to adopt a treatment practice based on the cost to the organization, whether the treatment would benefit patients in a meaningful way (e.g., enhance their quality of life) and whether the treatment would be viewed as viable and beneficial by the related constituents (family members and staff). This study uniquely triangulates treatment satisfaction ratings between patients, family members, and hospice staff with qualitative and quantitative methods, providing for enhanced comparisons in dual modalities. Ideally, such results will facilitate implementation of Dignity Therapy within a “real-world” hospice setting.
2009 Clinical Awardees
Awardee: Maple Fung, MD
Effects of variation in the degree of African admixture on renal disease and candidate adrenergic genes in African-American veterans
Awardee: Karen Herbst, MD, PhD
Blockade of Receptor Cleavage in Diabetes Mellitus with an MMP Inhibitor
2008 Clinical Awardees
Awardee: Miguel Goicoechea, MD, Assistant Adjunct Professor of Medicine
UCSD HIV Therapy: Impact of Inhibition of Cellular Drug Transporters on
Intracellular Nucleoside Analogue Triphosphate Concentrations
Awardee: Barbara H. Jung, MD, Assistant Professor of Medicine, UCSD
BARD1 Splice Variants and Colon Cancer Metastasis
Awardee: Jing Yang, MD, Assistant Professor of Pharmacology, UCSD
Dissecting the Molecular Basis of Ewing's Sarcoma Metastasis