Li Li
University Of California Los Angeles
Project start date: 2007-09-27
Project end date: 2012-08-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Li Li
POL AND ACCESS INTERVENTION TO REDUCE HIV STIGMA AMONG SERVICE PROVIDERS IN CHINA
Li Li
University Of California Los Angeles, Office Of Research Administration, Los Angeles, Ca 90095
Grant 5R01MH081778-04 from National Institute Of Mental Health
Abstract: We propose a four-year intervention trial that will address both individual and structural components to reduce HIV-related stigma among service providers in China. As the demand for HIV treatment and care increases rapidly, service providers in China are at a critical point with growing responsibilities to deliver adequate services and care for patients living with HIV (PLH). However, HIV-related stigma in health care setting has a tremendous impact on PLH´s health outcomes, health seeking behavior, and treatment adherence. This proposed study builds on a three-year pilot study conducted from 2003 to 2006 with 1,344 among service providers in China. We have identified the need to address HIV-related stigma by building a social norm of acceptance while addressing the environmental barriers - access to universal precaution. China CDC has committed to providing universal precaution supplies to all participating hospitals for this study, including those in the standard care condition. Incorporating all core elements of the Popular Opinion Leader (POL) model, the proposed intervention will have four training sessions and bi-monthly reunion sessions. We plan to train 600 POL providers in 20 intervention hospitals. The intervention trial will proceed in two phases. In Phase 1, we will test and finalize the intervention activities, assessment measures and implementation procedures with small samples of service providers and patients from two county hospitals. We will also recruit and train staff and establish quality assurance procedures as well as data encryption and data transfer processes. In Phase 2, we will conduct a randomized controlled trial to evaluate the impact of the intervention in 40 hospitals in Yunnan and Fujian, China, with 1,760 service providers at baseline, 6 and 12-month follow-ups. We will also assess impact of the intervention on patients with three waves of cross-sectional patient surveys (n=1,000/wave). The provider outcomes are providers´ attitude and behavior changes. The patient outcomes are patients´ perceived stigma, medical service utilization, and satisfaction and treatment adherence. We will collect data through various approaches including self-report, behavioral observation, and using standardized patients (trained staff used to evaluate provider´s performance). The number of annual reported HIV infections in China has increased steadily. The China Ministry of Health estimated the total number of PLH at 650,000 by the end of 2005. With one-fifth of the world´s population, the potential devastation of a rapidly growing HIV pandemic in China is staggering, and effective measures to prevent and control the spread of HIV/AIDS in China are urgently needed. HIV-related stigma in medical settings discourages PLH from seeking care if they previously experienced unwelcoming treatment or their confidentiality was not protected. As a result, fear of discrimination has created a reluctance to deal with HIV-related matters, which threatens public health and has direct negative consequences on quality of life for PLH. The proposed study will be the first randomized controlled intervention trial that specifically targets stigma and access to universal precautions in medical settings, and is implemented at multiple sites (two provinces) in China
Keywords: AIDS; AIDS Seroconversion; AIDS Seropositivity; AIDS Virus; AIDS test; AIDS/HIV; AIDS/HIV problem; AIDS/HIV test; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immune Deficiency Syndrome Virus; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Acquired Immunodeficiency Syndrome Virus; Address; Adherence; Adherence (attribute); Age; Annual Reports; Anti-HIV Positivity; Anti-Retroviral Agents; Antiretroviral Agents; Attitude; Behavior; Behavior Conditioning Therapy; Behavior Modification; Behavior Therapy; Behavior Treatment; Behavior or Life Style Modifications; Behavioral; Behavioral Conditioning Therapy; Behavioral Modification; Behavioral Therapy; Behavioral Treatment; CDC; Care, Health; Caring; Centers for Disease Control; Centers for Disease Control (U.S.); Centers for Disease Control and Prevention; Centers for Disease Control and Prevention (U.S.); China; Chinese; Chinese People; Cognitive Discrimination; Commit; Communicable Diseases; Communities; Community Services; Compassion; Conditioning Therapy; Confidentiality; County Hospitals; Data; Diffuse; Diffusion; Discrimination; Discrimination (Psychology); Drug abuse; Drug usage; Elements; Ethnic Origin; Ethnicity; Ethnicity aspects; Exhibits; Fear; Fright; Gender; Government; HIV; HIV Antibody Positivity; HIV Infections; HIV Positive; HIV Positivity; HIV Seroconversion; HIV Seropositivity; HIV test; HIV/AIDS; HIV/AIDS problem; HOSP; HTLV-III; HTLV-III Infections; HTLV-III Seroconversion; HTLV-III Seropositivity; HTLV-III-LAV Infections; Health; Health Care Seeking Behavior; Health Care Utilization; Healthcare; Hepatitis B; Hepatitis B Infection; Hospital Sizes; Hospitals; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus test; Immunologic Deficiency Syndrome, Acquired; Individual; Infection; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Intervention; Intervention Strategies; Intervention Trial; Judgment; Knowledge; LAV-HTLV-III; Learning; Length; Life; Life Style Modification; Location; Lymphadenopathy-Associated Virus; Mainland China; Marketing; Measures; Medical; Modeling; Outcome; PROV; Participant; Patient Care; Patient Care Delivery; Patient Education; Patient Instruction; Patient Self-Report; Patient Training; Patients; Performance; Personal Satisfaction; Phase; Pilot Projects; Policies; Population; Prevalence; Preventive; Procedures; Process; Programs (PT); Programs [Publication Type]; Provider; Province; Public Health; QOL; Quality of life; Quarantine; Randomized; Randomized Controlled Trials; Recruitment Activity; Reporting; Risk; Risk Behaviors; Risky Behavior; Route; Rural; Safety; Sampling; Self-Report; Services; Site; Stigmata; Survey Instrument; Surveys; T-Lymphotropic Virus Type III Infections, Human; Test Result; Testing; Training; Transmission; United States Centers for Disease Control; United States Centers for Disease Control and Prevention; Universal Precautions; Viral Hepatitis B; Virus-HIV; Work; ing; abuse of drugs; abuses drugs; anti-retroviral; antibody positive AIDS test; antigen positive AIDS test; antiretroviral; at risk behavior; base; behavior change; behavior intervention; behavior observation; behavioral intervention; behavioral observation; care seeking; cohort; design; designing; drug use; encryption; experience; health care service utilization; health seeking behavior; health services utilization; healthcare service utilization; healthcare utilization; high risk; interventional strategy; isolation/quarantine; pandemic; pandemic disease; pilot study; prevent; preventing; privacy of information; programs; public health medicine (field); quality assurance; randomisation; randomization; randomized controlled study; randomly assigned; recruit; satisfaction; seropositive (AIDS test); serum hepatitis; service utilization; sex; social; social stigma; standard care; stigma; transmission process; treatment adherence; treatment utilization; well-being
Project start date: 2007-09-27
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: PA-07-070
5R01MH081778-04 (2010): $481963
5R01MH081778-03 (2009): $530442
5R01MH081778-02 (2008): $518959
1R01MH081778-01A1 (2007): $633823
DEVELOPMENT OF A FAMILY INTERVENTION TO ADDRESS DRUG USE AND HIV IN VIETNAM
Li Li, Professor In Residence
University Of California Los Angelescity: Los Angeles country: United States (us)
Grant 5R34DA029493-02 from National Institute On Drug Abuse
Abstract: Vietnam is experiencing two epidemics - injection drug use and HIV. Most young injection drug users (IDU) have daily family contact or live with their family, and the burden on the family is substantial, even greater if the IDU is HIV+. It is the families´ support and coping that determines how well the IDU meets four lifelong challenges to improve physical and mental health; to reduce or manage drug use behaviors; to reduce sexual risk; and to maintain positive family relationships. We hypothesize that with assistance, families can be part of the solution for both HIV- and HIV+ IDU. In this study, we propose an intervention pilot study that will develop and evaluate a family intervention to improve outcomes over time for IDU and their families in Vietnam. The proposed study is a collaborative effort between UCLA and Vietnam National Institute of Hygiene and Epidemiology (NIHE) and will proceed in two phases. In Phase 1, with in-depth interviews and a focus group, we will get qualitative data on 1) the perceived social, behavioral, health and mental health challenges for HIV- and HIV+ IDU; 2) family burden of drug use and HIV; 3) desirable intervention delivery formats; and 4) feasible strategies for improving services and care to HIV+ IDU. Based on the findings, we will develop a Vietnamese- specific family intervention for IDU and their families and review intervention contents and delivery strategies to ensure the program will be culturally appropriate and acceptable. In Phase 2, we will pilot the intervention in Phu Tho, Vietnam. Both HIV+ (n=40) and HIV- IDU (n=40) will be recruited through two drug rehabilitation centers in Phu Tho. Each IDU participant will be asked for consent to recruit a family member (n=80). We will then pilot the intervention by comparing the adjustment of IDU and their family members over 3 and 6 months, who are randomly assigned to receive either 1) a family intervention; or 2) the standard care. HIV infection is rising exponentially in Vietnam, primarily among injection drug users (IDU), creating a window of opportunity to intervene with IDU before HIV reaches the general population. Most IDU in Vietnam have daily family contact or live with their family, and the psychosocial burdens on the family members are substantial and the families´ support and coping determines how well IDU can manage their challenges. We propose an intervention pilot study that will develop and evaluate a family intervention to improve outcomes over time for IDU and their families in Vietnam
Keywords: Address; Advocate; Affective; Asia; base; Behavior; behavior change; Behavioral; behavioral health; Belief; Caregiver Burden; Caring; China; Cognitive; cohesion; Collaborations; Communities; Consent; coping; Country; Data; design; Development; Disclosure; District Hospitals; Drug Rehabilitation Centers; Drug usage; Educational workshop; Ensure; Epidemic; Epidemiologic Studies; Epidemiologist; Epidemiology; Evidence based intervention; experience; Family; Family member; Family Relationship; Focus Groups; follow-up; General Population; group intervention; Harm Reduction; Health; Health behavior; Health Status; Healthcare Systems; HIV; HIV Infections; Home environment; Human immunodeficiency virus test; Hygiene; improved; Injecting drug user; Injection of therapeutic agent; Institutes; Intervention; Intervention Studies; Interview; Life; Mediating; meetings; Mental Health; Outcome; Parents; Participant; Pharmaceutical Preparations; Phase; physical conditioning; Pilot Projects; Procedures; programs; Provider; psychosocial; public health relevance; Quality of life; Randomized; Recruitment Activity; Research Design; Risk; Risk Behaviors; Role; Security; Series; Services; skills; social; social stigma; Social support; Solutions; South Africa; Specialist; standard care; Stigmata; stress management; symptom management; Symptoms; Thailand; Time; treatment adherence; United States; Vietnam
Relevance: HIV infection is rising exponentially in Vietnam, primarily among injection drug users (IDU), creating a window of opportunity to intervene with IDU before HIV reaches the general population. Most IDU in Vietnam have daily family contact or live with their family, and the psychosocial burdens on the family members are substantial and the families´ support and coping determines how well IDU can manage their challenges. We propose an intervention pilot study that will develop and evaluate a family intervention to improve outcomes over time for IDU and their families in Vietnam
Project start date: 2010-07-15
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-09-146
5R34DA029493-02 (2011): $291766
1R34DA029493-01 (2010): $300501
ELUCIDATING THE ROLES OF GLUR1 AND BDNF IN TRANS-SYNAPTIC COORDINATION
Li Li
Stanford Universitycity: Stanford country: United States (us)
Grant 5F30MH093125-02 from National Institute Of Mental Health
Abstract: Understanding how a neural circuitry is modified from experience or in disease requires a fundamental understanding of how presynaptic changes in transmitter release coordinate with postsynaptic changes in response. I study a model of neuronal adaptation to chronic inactivity in which the postsynaptic expression of surface GluR1-containing 1-amino-3-hydroxyl-5-methyl-4- isoxazole-propionate (AMPA) receptors is increased during the inactivity while the rate of presynaptic release increases after inactivity relief. In addition, this increase in presynaptic release requires flux through the postsynaptic GluR1-containing AMPA receptors and the signaling of brain-derived neurotrophic factor (BDNF). These observations suggest the existence of a post-to-pre trans-synaptic coordination in which GluR1-containing AMPA receptors may initiate the postsynaptic events and BDNF may as a retrograde messenger to regulate presynaptic function. However, the roles of GluR1 and BDNF in this trans-synaptic coordination are incompletely understood and their relationship is unclear. To address these gaps in understanding, I will use biochemical, genetic, electrophysiological and optical methods to determine 1) how GluR1-containing AMPA receptors selectively accumulate at the postsynapse, 2) whether BDNF is a retrograde messenger, and 3) how GluR1-containing receptors regulate BDNF signaling. Elucidating the roles of GluR1 and BDNF in trans-synaptic coordination will advance our fundamental understanding of plasticity mechanisms and is likely to provide insights into diseases in which synaptic function is defective such as in Alzheimer´s disease and in epilepsy. My research in understanding the molecular mechanisms underlying connective changes in neural circuitry can lead to new insights into mental disorders, one of the leading causes of disability in the United States. Moreover, these insights can provide new therapeutic targets, open new avenues of treatments, and pave the road to potential cures for these disorders. Thus, the long-term goal of this research is to improve public health with discoveries that can improve mental health
Keywords: Address; Alteplase; Alzheimer`s Disease; AMPA Receptors; Autocrine Communication; Behavior; Biochemical; Biochemical Genetics; Brain-Derived Neurotrophic Factor; Calcium; Chronic; Dependence; disability; Disease; Endosomes; Environment; Epilepsy; Event; experience; extracellular; Fluorescence; Frequencies (time pattern); Genetic; GluR2 subunit AMPA receptor; Goals; Hippocampus (Brain); Hydroxyl Radical; improved; Infusion procedures; insight; Isoxazoles; knock-down; Lead; Learning; Link; Location; Mental disorders; Mental Health; Modeling; Molecular; Nature; neural circuit; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; new therapeutic target; novel; Optical Methods; Pharmacology; PHluorin; Physiological; postsynaptic; presynaptic; prevent; Probability; Process; Propionates; Proteins; public health medicine (field); public health relevance; receptor; Receptor Signaling; red fluorescent protein; Research; response; RNA Interference; Role; Signal Transduction; Site; Source; Surface; Synapses; synaptic function; Testing; Time; trafficking; Travel; United States; Vesicle; Work
Relevance: My research in understanding the molecular mechanisms underlying connective changes in neural circuitry can lead to new insights into mental disorders, one of the leading causes of disability in the United States. Moreover, these insights can provide new therapeutic targets, open new avenues of treatments, and pave the road to potential cures for these disorders. Thus, the long-term goal of this research is to improve public health with discoveries that can improve mental health
Project start date: 2010-09-15
Project end date: 2012-09-14
Budget start date: 15-SEP-2011
Budget end date: 14-SEP-2012
PFA/PA: PA-10-107
5F30MH093125-02 (2011): $31658
1F30MH093125-01 (2010): $30857
Li Li
University Of California San Francisco, 3333 California St., Ste 315, San Francisco, Ca 94143-0962
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Percentile Analysis for Differential Gene Expression (PADGE) is a novel tool for identifying genes differentially expressed between two groups of heterogeneous samples. PADGE was designed to compare expression profiles of sample subgroups at a series of percentile cutoffs and to examine the trend of relative expression between sample classes as expression level increases. For comparative analysis, all sample statistical analysis (t test or Wilcoxon rank sum test), the COPA approach (Tomlins et al, Science, 2005) and Kurtosis (Teschendorff, et al, Bioinformatics, 2006) are also implemented and their results are displayed side by side with PADGE, providing a resource of web-based tools for analysis of heterogeneous expression patterns
Keywords: Bio-Informatics; Bioinformatics; Biomedical Computing; CRISP; Computer Retrieval of Information on Scientific Projects Database; Differential Gene Expression; Expression Profiling; Expression Signature; Funding; Genes; Grant; Imagery; Informatics; Institution; Investigators; Molecular Fingerprinting; Molecular Profiling; NIH; National Institutes of Health; National Institutes of Health (U.S.); On-Line Systems; Online Systems; Pattern; Rank-Sum Tests; Relative; Relative (related person); Research; Research Personnel; Research Resources; Researchers; Resources; SUBGP; Sampling; Science; Series; Side; Source; Subgroup; Testing; Tissue-Specific Differential Gene Expression; Tissue-Specific Gene Expression; United States National Institutes of Health; Visualization; bio-computation; bio-computing; biocomputing; biomedical computation; comparative; design; designing; molecuar profile; molecular signature; novel; online computer; tool; trend; web based
Project start date: 2009-07-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
5P41RR001081-32_5755 (2009): $8911
TEA FOR FAMILIES AND CHILDREN: A RANDOMIZED INTERVENTION TRIAL
Li Li, Professor In Residence
University Of California Los Angelescity: Los Angeles country: United States (us)
Grant 1R01HD068165-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: This 5-year project is a randomized controlled trial of the TEA (Together for Empowerment Activities) intervention. TEA intervention is an innovative, theoretically-based, culturally sensitive family intervention for HIV-affected families in rural China. The intervention will have six sessions (plus a preparation session) delivered at three levels simultaneously 1) TEA Gathering (small group for parents living with HIV (PLH) and their family members), 2) TEA Time (home-based family activities with children), and 3) TEA Garden (community events). Built on the extensive pilot work by the collaborative team in the past 5 years, we propose to conduct the randomized controlled trial of TEA intervention with 480 HIV-affected families in 24 villages in Anhui, China, including 480 PLH, 480 sero-negative family members, and 720 children aged 6-18. We will randomly assign villages to either 1) TEA intervention group (with all three levels of activity), or 2) a control group (with limited activities). The efficacy the intervention will be determined over 24 months at five time points baseline, 6, 12, 18, and 24 month follow-ups. The primary outcomes are children´s physical health, mental health and behavioral adjustment. Secondary outcomes will be the PLH´s and family members´ physical health, mental health, and quality of life, as well as family indicators such as consistent daily routines, positive family interactions, parenting, coping, and community integration. The need to respond to the HIV epidemic is a global public health priority. The proposed study responds to the urgent need for interventions for PLH, family members, and children impacted by HIV/AIDS in China. Resulting data will provide an evidence-based intervention that can be delivered to HIV-affected families in China and other countries
Keywords: Address; Affect; Age; aged; AIDS/HIV problem; base; Behavioral; Caregivers; Caring; Child; Child Care; China; Communities; Community Integration; Community Networks; Control Groups; coping; Country; County; Data; design; Development; Economics; efficacy testing; Emotional; empowerment; Epidemic; Event; Evidence based intervention; experience; Extended Family; Face; Family; Family member; follow-up; grandchild; grandparent; group intervention; Growth; HIV; Home environment; improved; innovation; Intervention; Intervention Trial; Learning; Life; Location; Mediating; Mental Health; Needs Assessment; Outcome; Parenting behavior; Parents; Pathway interactions; Pattern; Persons; physical conditioning; pilot trial; Policies; Population; Preparation; Prevalence; primary outcome; programs; public health priorities; public health relevance; Quality of life; Randomized; Randomized Controlled Trials; randomized trial; Relative (related person); Research; Rural; rural area; Schools; secondary outcome; skills; Social support; Spouses; Testing; Time; Treatment Efficacy; Work
Project start date: 2011-05-01
Project end date: 2016-02-29
Budget start date: 1-MAY-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-10-067
1R01HD068165-01 (2011): $545783
Sponsored Links Excellgen http://Excellgen.com
TEA FOR FAMILIES & CHILDREN: PREPARATION FOR A RANDOMIZED TRIAL
Li Li, Director
University Of California Los Angeles, Office Of Research Administration, Los Angeles, Ca 90095
Grant 5R01MH080606-02 from National Institute Of Mental Health
Abstract: This 2-year project is a preparation and pilot phase for a randomized controlled trial of the TEA (Together for Empowerment Activities) intervention, a family intervention for HIV-affected families in China. TEA intervention will have 10 sessions (plus a preparation session) delivered at three levels simultaneously 1) TEA Gathering (small group for parents living with HIV (PLH) and their family members), 2) TEA Time (home- based family activities with children that accompany each TEA Gathering), and 3) TEA Garden (community events that build social integration for families living with HIV). Built on the extensive pilot work by the collaborative team, this study will focus on the preparation and pilot activities, including finalizing the TEA intervention, implementation and assessment procedures and a pilot with 40 HIV-affected families in 4 villages (2 in the intervention group and 2 in the control group). The feasibility, acceptability, and accessibility of the intervention will be assessed through process evaluation. The preliminary impact of the intervention will be assessed by comparing the outcomes measures at baseline and 3-month follow-up. The primary outcomes are children´s health, mental health, and behavioral adjustment. The secondary outcomes will be the PLH´s and family members´ health, mental health, and quality of life, as well as family indicators such as consistent daily routines, positive interactions, parenting, coping, and community integration. Interventions that address the challenges that families face, provide information, build families´ skills, and form supportive local community networks are needed. This project will provide such an intervention. The goal of this study is to develop and pilot an intervention for PLH and their family members in order to improve the long term health, mental health and behavioral adjustment of the children in poor, rural areas in China
Keywords: 0-11 years old; AIDS Virus; AIDS/HIV; AIDS/HIV problem; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Active Follow-up; Address; Affect; Age; Asia; Behavioral; Caring; Child; Child Care; Child Youth; Child health care; Children (0-21); China; Communities; Community Integration; Community Networks; Conditions, Economic; Conditions, Economical; Control Groups; Country; Data; Development; Economic Conditions; Economics; Emotional; Epidemic; Evaluation; Event; Extended Family; Face; Family; Family Relations; Family Relationship; Family member; Feedback; Feeling; Funding; Gatekeeping; Generalized Growth; Goals; Growth; HIV; HIV/AIDS; HIV/AIDS problem; HTLV-III; Health; Health, Child; Home; Home environment; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human, Child; Intervention; Intervention Strategies; LAV-HTLV-III; Learning; Life; Light; Lymphadenopathy-Associated Virus; Mainland China; Manuals; Married Persons; Measures; Mental Health; Mental Hygiene; News; News (PT); News [Publication Type]; Outcome Measure; Parents; Participant; Pathway interactions; Pattern; Persons; Phase; Photoradiation; Population; Preparation; Prevalence; Procedures; Process; Psychological Health; Puericulture; QOL; Quality of life; Randomized; Randomized Controlled Trials; Recruitment Activity; Relative; Relative (related person); Reporting; School Teachers; Schools; Social support; Spouses; Symptoms; Time; Tissue Growth; Training; United Nations; Virus-HIV; Work; aged; base; children; coping; empowerment; encryption; facial; feelings; follow-up; gatekeeper; grandchild; grandparent; group intervention; improved; interventional strategy; news; ontogeny; pathway; primary outcome; public health relevance; quality assurance; randomisation; randomization; randomized controlled study; randomized trial; randomly assigned; recruit; rural area; secondary outcome; skills; social integration; social support network; youngster
Relevance: Interventions that address the challenges that families face, provide information, build families´ skills, and form supportive local community networks are needed. This project will provide such an intervention. The goal of this study is to develop and pilot an intervention for PLH and their family members in order to improve the long term health, mental health and behavioral adjustment of the children in poor, rural areas in China
Project start date: 2009-04-01
Project end date: 2011-03-31
Budget start date: 1-APR-2010
Budget end date: 31-MAR-2011
PFA/PA: PA-07-070
5R01MH080606-02 (2010): $365408
Genetic Epidemiology Of Insulin Resistance Pathway Factors And Colon Cancer
Li Li
Family Medicinecase Western Reserve University
10900 Euclid Ave
cleveland, Oh 441064919
Grant 5K22CA120545-03 from National Cancer Institute IRG: NCI
Abstract: The proposed K22 award will support the transition of Li Li, M.D., Ph.D. from a mentored to an independent cancer genetic epidemiology investigator. During his mentored research supported by Damon Runyon Cancer Research Foundation, he has developed his expertise in cancer genetic/molecular epidemiology focusing on gene-environment interaction, and established a Kentucky SEER Registry-based incident case-control study of colon cancer. This study has already collected blood samples and data from over 580 cases and population controls, and it is anticipated that a total of 1,100 cases and controls will be accrued and available for this application by the end of his mentored Clinical Investigator Award. The K22 proposal will address the insulin resistance-colon cancer hypothesis by looking at the relation of insulin resistance syndrome as an integral entity with colon cancer using a novel structure equation model approach. This study holds promise of gaining novel and critical insight into the insulin resistance-colon link that might have been missed or distorted in studies using the conventional ´independent risk factor finding´ regression analysis by treating each of the metabolic components of the syndrome as independent covariates. In addition, this K22 proposal will comprehensively evaluate SNPs and haplotypes of 9 candidate genes in three molecular pathways and two environmental factors, i.e., physical activity and non-steroidal anti-inflammatory drugs (NSAIDS), implicated in the development of insulin resistance and colon carcinogenesis. Specifically, this proposal has the following aims 1) To assess the relation of insulin resistance syndrome as an integral entity with colon cancer; 2) To examine the relations of colon cancer with SNPs and haplotypes of 9 candidate genes in three molecular pathways (i) insulin-growth hormone-IGF-insulin receptor substrate axis, (ii) inflammation, and (iii) adipogenesis; 3) To investigate the direct and indirect (i.e., mediated by insulin resistance) effects of these genetic and environmental factors on colon cancer. This research will fill current knowledge gaps in understanding the underlying link between insulin resistance resulting from long-term energy imbalance and colon cancer. It will set the stage for a planned full R01 application to seek national funding to expand the current effort to a fully powered study to tackle gene-environment joint action under the unifying theme of insulin resistance-colon cancer hypothesis
Project start date: 2006-09-01
Project end date: 2009-08-31
5K22CA120545-03 (2008): $155808
5K22CA120545-02 (2007): $155938
1K22CA120545-01 (2006): $156060
CHROMATIN REMODELING IN SMOOTH MUSCLE MYOGENESIS AND VASCULAR INJURY RESPONSES
Li Li, Associate Professor
Wayne State Universitycity: Detroit country: United States (us)
Grant 5R01HL087014-05 from National Heart, Lung, And Blood Institute
Abstract: The long-term goal of this project is to understand the molecular mechanisms that regulate smooth muscle cell (SMC) phenotypic changes during smooth muscle myogenesis and in the pathogenesis of human vascular diseases. Recent extensive biochemical and genetic studies have provided substantial evidence showing that the balance of histone acetylation and deacetylation is crucial to the control of cell proliferation in cancer and cardiac hypertrophy. However, little is known about how manipulating histone acetylation controls SMC gene transcription and proliferation in human vascular diseases. The goal of this application is to determine the molecular mechanisms whereby histone modifiers, especially HDAC8, regulate SMC gene transcription both in vitro and in vivo. This study integrates innovative transgenic/knockout mice, BAG recombineering and bioinformatics tools into classic biochemical, molecular and developmental biology approaches. The results of this study will not only fill a gap in our understanding of HDACs in transcriptional regulation, but also further our knowledge of epigenetic mechanisms in regulating SMC myogenesis^ Extensive studies demonstrate that the dynamic changes of histone acetylation and deacetylation play important roles in gene transcription and cell proliferation. HDACS is a member of the class I HDAC (histone deacetylase) family, and possesses histone deacetylase activities. Our preliminary results show that HDACS, unlike other HDACs, acts as a transcriptional activator for SMC gene transcription. We hypothesize that HDACS is a pro-SMC differentiation factor that modulates SRF/Myocardin and SmadS-mediated SMC transcriptional regulatory complexes. The specific aims are (1) to determine whether HDACS affects histone modification at the SM22 locus in vitro, and whether the deacetylase activity of HDACS is required to enhance the pro-myogenic activities of SMC regulators; (2) to determine how HDACS interacts with the SMC transcriptional regulatory network and TGFpl signal pathway; (3) to determine whether histone deacetylase inhibitors affect atherogenesis and how HDACS modulates SMC differentiation in SMC myogenesis and in injury-induced restenosis in vivo. Given the important roles of histone modification in SMC growth and differentiation, the results of this study will contribute significantly towards developing novel therapeutical strategies targeted at the epigenetic mechanisms affecting the abnormal SMC-associated human vascular diseases
Keywords: Affect; Arteries; atherogenesis; Binding (Molecular Function); Biochemical; Biochemical Genetics; Bioinformatics; Biological Assay; Blood Vessels; Boxing; Cell Differentiation process; cell growth; Cell Line; Cell Proliferation; Cells; Chromatin; chromatin remodeling; Complex; Core Facility; Coronary artery; COS Cells; Deacetylase; Developmental Biology; Embryo; Epigenetic Process; Equilibrium; Family; Fibroblasts; Genetic Transcription; Goals; Heart Hypertrophy; Histone Acetylation; histone acetyltransferase; Histone Deacetylase; Histone Deacetylase Inhibitor; Histone Deacetylation; Histone H3; Histone H4; histone modification; Histones; Human; In Vitro; in vivo; injured; Injury; innovation; Knockout Mice; Knowledge; Malignant Neoplasms; Medial; Mediating; member; Methylation; Michigan; Molecular; Molecular Biology; mouse model; Mus; mutant; Mutation; myocardin; Myofibroblast; myogenesis; novel; overexpression; Pathogenesis; Pattern; Physical condensation; Play; Promotor (Genetics); Recruitment Activity; Research Personnel; response; response to injury; restenosis; Role; Services; Signal Pathway; Smooth muscle (tissue); Smooth Muscle Myocytes; Sodium Butyrate; stable cell line; Testing; TGFB1 gene; tool; Transcription Coactivator; Transcriptional Activation; Transcriptional Regulation; Transgenic Mice; Transgenic Organisms; Trichostatin A; Universities; Vascular Diseases
Project start date: 2007-07-06
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5R01HL087014-05 (2011): $376250
5R01HL087014-04 (2010): $376250
5R01HL087014-03 (2009): $376250
5R01HL087014-02 (2008): $376250
1R01HL087014-01A1 (2007): $376250
Sponsored Links Excellgen http://Excellgen.com
METHADONE MAINTENANCE AND HIV PREVENTION: A WINDOW OF OPPORTUNITY IN CHINA
Li Li
University Of California Los Angelescity: Los Angeles country: United States (us)
Grant 5R34MH083512-03 from National Institute Of Mental Health
Abstract: The implementation of the MMT program in China is one of the most significant measures ever taken by the Chinese government to tackle drug use and HIV prevention challenges, and the effectiveness of these programs has implications for HIV and drug use control. Several pilot studies have identified high client drop-out rate, insufficient training of service providers and limited client service as the main challenges these programs face. We propose to take this window of opportunity to address these challenges by developing and testing an intervention, MMT PLUS, to be added on to the current MMT standard care in China. The proposed MMT PLUS intervention is designed primarily for service providers who work at MMT clinics. The proposed intervention pilot will take 2.5 years and proceed in two phases in Sichuan, China. In Phase 1, we will develop intervention manuals and supporting materials, and finalize assessment measures and implementation procedures. We will also recruit and train staff, establish quality assurance procedures and data encryption and data transfer processes. In Phase 2, we will conduct the pilot intervention across 6 MMT clinics involving 30 service providers and 150 MMT clients, and follow up at 3, 6, and 9-month period. The service provider outcomes are adherence to MMT protocol, reduction in prejudicial attitude toward MMT clients, increase in comfort working with MMT clients, and increase in motivating clients and making personalized risk management plan. The client outcomes are increased motivation to change, improved psychological and physical health, increased positive support network, and reduced HIV risk behavior. China CDC, the collaborating agency for this study, is the leading force in implementing the current MMT program and has committed to develop new, innovative MMT models for nation-wide dissemination. The findings of this pilot could provide benefits for China and beyond by advancing the field through the sharing of our experience and the lessons learned in integrating a behavioral intervention into a primarily pharmacological model of methadone maintenance, and in transferring timely program development findings to country-wide implementation and policy-making
Keywords: Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Active Follow-up; Address; Adherence; Adherence (attribute); Age; AIDS prevention; AIDS Virus; AIDS/HIV; AIDS/HIV prevention; AIDS/HIV problem; Applaud; at risk behavior; Attention; Attitude; Behavior Conditioning Therapy; behavior intervention; Behavior Modification; Behavior or Life Style Modifications; Behavior Therapy; Behavior Treatment; Behavioral; Behavioral Conditioning Therapy; behavioral intervention; Behavioral Modification; Behavioral Therapy; Behavioral Treatment; C 1 Esterase; C1 Esterase; C1 s; C1s; CDC; Centers for Disease Control; Centers for Disease Control (U.S.); Centers for Disease Control and Prevention; Centers for Disease Control and Prevention (U.S.); China; Chinese; Chinese People; Client; Clinic; Commit; Communities; Complement 1 Esterase; Complement 1s; Complement component C1s; Conditioning Therapy; Country; Data; design; designing; Drops; Drug Controls; Drug usage; drug use; Drug user; Effectiveness; Employment; encryption; Epidemic; Evaluation; experience; Face; facial; Family; Feedback; follow-up; Gender; Gills; Government; group intervention; History; HIV; HIV Prevention; HIV/AIDS; HIV/AIDS prevention; HIV/AIDS problem; HTLV-III; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; improved; innovate; innovation; innovative; Intervention; intervention design; Intervention Strategies; interventional strategy; Knowledge; LAV-HTLV-III; Learning; Life Style Modification; Link; Lymphadenopathy-Associated Virus; Mainland China; Manuals; Measures; Mental Health; Mental Hygiene; methadone maintenance; Modeling; Models, Theoretic; Motivation; Outcome; Participant; Phase; physical conditioning; Pilot Projects; pilot study; Policy Making; Population; primary outcome; Procedures; Process; Professional Education; Program Development; Program Effectiveness; programs; Programs (PT); Programs [Publication Type]; Protocols, Treatment; PROV; Provider; Province; psychologic; psychological; Psychological Health; psychosocial; public health relevance; quality assurance; randomisation; randomization; Randomized; randomly assigned; Recording of previous events; recruit; Recruitment Activity; Regimen; Reporting; Reportings, Hospital Risk; Research; RGM; Risk Behaviors; Risk Management; Risk Reporting, Hospital; Risky Behavior; secondary outcome; Series; service intervention; Services; skills; social stigma; Social support; social support network; standard care; stigma; Stigmata; Testing; Theoretical model; therapy design; Training; treatment design; treatment program; Treatment Protocols; Treatment Regimen; Treatment Schedule; United States Centers for Disease Control; United States Centers for Disease Control and Prevention; Virus-HIV; Work
Relevance: China CDC, the collaborating agency for this study, is the leading force in implementing the current MMT program and has committed to develop new, innovative MMT models for nation-wide dissemination. The findings of this pilot could provide benefits for China and beyond by advancing the field through the sharing of our experience and the lessons learned in integrating a behavioral intervention into a primarily pharmacological model of methadone maintenance, and in transferring timely program development findings to country-wide implementation and policy-making
Project start date: 2009-03-02
Project end date: 2012-02-29
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PAR-06-248
5R34MH083512-03 (2011): $61034
5R34MH083512-02 (2010): $260416
INTEGRATING LONGITUDINAL CHANGES IN MAMMOGRAPHIC DENSITY INTO RISK PREDICTION
Li Li, Assistant Professor
Case Western Reserve Universitycity: Cleveland country: United States (us)
Grant 1R03CA143917-01A1 from National Cancer Institute
Abstract: Project Summary Mammographic density (MD) is one of the strongest risk factors for breast cancer, but largely underused for risk assessment. Recent data have shown that incorporating a single ´baseline´ MD measure into the well known Gail model only slightly improves the model´s discriminatory power. Whether integration of trajectories of longitudinal change in MD further enhances the model´s predictive power has not been explored. We hypothesize that the general population is a mixture of heterogeneous sub-groups with regard to the developmental profile of MD, and the trajectories of change may not be completely captured by a single MD measurement. We further hypothesize that integration of longitudinal changes in MD into the Gail model will improve the model´s predictive power of individual risk. This study builds upon an ongoing pilot study where 655 breast cancer cases and 627 frequency-matched controls with 3 or more screening mammograms within the last 14 years are being recruited. All archived screening mammograms will be processed using a validated computer-assisted "interactive thresholding´ algorithm to assess patterns of longitudinal change in MD. We will use a novel latent growth mixture model to examine the association of longitudinal changes of MD with risk of breast cancer, and to evaluate the risk prediction power of a refined Gail model that incorporates information on the longitudinal developmental profiles of MD. This study may have important implication for risk prediction. Refined Gail model may enhance the model´s predictive ability to identify high-risk individuals, and better guide the initiation of chemoprevention and interventions. This study builds upon an ongoing pilot study where 655 breast cancer cases and 627 healthy controls with 3 or more screening mammograms within the last 14 years are being recruited. This unique study population, each participant with at least 3 or more screening mammograms, will be readily available and allow us to explore whether integration of longitudinal changes in mammographic density over time would enhance the discriminatory power of the well known Gail model for breast cancer risk assessment
Keywords: (Z)-2-[4(1, 2-diphenyl-1-butenyl)-phenoxyl]-N, N-dimethylethanamine; 1-p-beta-dimethylamino-ethoxyphenyl-trans-1, 2-diphenylbut-1-ene; Address; Algorithms; Archives; base; Breast; Breast Cancer Gail Model; Breast Cancer Gail Model Risk Assessment Tool; Breast Cancer Risk Assessment Tool; Breast Cancer Risk Factor; breast density; Cancer of Breast; cancer risk; Cancers; Case-Base Studies; Case-Comparison Studies; Case-Compeer Studies; Case-Control Studies; Case-Referent Studies; Case-Referrent Studies; Chemoprevention; computer aided; Computer Assisted; computer based prediction; Data; Development; Environmental Factor; environmental risk; Environmental Risk Factor; Epidemiology; Ethanamine, 2-(4-(1, 2-diphenyl-1-butenyl)phenoxy)-N, N-dimethyl-, (Z)-; Frequencies (time pattern); Frequency; Gail model; General Population; General Public; Generalized Growth; Genetic Risk; Growth; high risk; improved; Individual; Individual Differences; Intervention; Intervention Strategies; interventional strategy; Keoxifene; malignancy; malignant breast neoplasm; Malignant neoplasm of breast; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Breast; Mammogram; Mammographic Density; Mammography; Measurement; Measures; Methods; MMG; Modeling; neoplasm/cancer; novel; ontogeny; Participant; Pattern; Pilot Projects; pilot study; Population; Population Study; predictive modeling; preventional intervention strategy; Preventive Intervention; Process; prophylactic; prospective; public health relevance; Raloxifene; recruit; Recruitment Activity; Risk; Risk Assessment; screening; Screening procedure; screenings; Stratification; TAM; Tamoxifen; Time; Tissue Growth; Woman; [6-Hydroxy-2-(4-hydroxyphenyl)-benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]metha
Relevance: This study builds upon an ongoing pilot study where 655 breast cancer cases and 627 healthy controls with 3 or more screening mammograms within the last 14 years are being recruited. This unique study population, each participant with at least 3 or more screening mammograms, will be readily available and allow us to explore whether integration of longitudinal changes in mammographic density over time would enhance the discriminatory power of the well known Gail model for breast cancer risk assessment
Project start date: 2011-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PAR-08-237
1R03CA143917-01A1 (2011): $78500
OBESITY-RELATED INSULIN RESISTANCE SIGNALING PATHWAY FACTORS AND COLON CANCER
Li Li, Assistant Professor
Case Western Reserve Universitycity: Cleveland country: United States (us)
Grant 5R01CA136726-03 from National Cancer Institute
Abstract: Obesity is now established as a potential cause for colon cancer. While the underlying mechanisms mediating the obesity-colon cancer link are not well understood, increasing evidence supports that Insulin resistance resulting from long-term energy imbalance and subsequent perturbation of metabolic homeostasis and insulin signaling pathways form the core of obesity-related colon carcinogenesis. Genetic variations within genes in key insulin and growth factor signaling pathways may, or in combination with obesity, drive the development of colon cancer, but have been little studied. The fact that obesity is escalating as an epidemic worldwide makes the exploration of the mechanistic connections between obesity and colon cancer a pressing public health and research priority. Therefore, we propose a genetic epidemiologic study of the relation of colon cancer with obesity and candidate genes in four critical insulin and related growth factor signaling pathways 1) phosphatidylinositol-3 Kinase/protein kinase B (PI3K/AKT) signaling cascade; 2) AMP-activated protein kinase (AMPK) pathway; 3) mitogen-activated protein (MAP) kinase pathway; and 4) peroxisome proliferators-activated receptors (PPARs). Each of these pathways plays an important role linking increased adiposity to colon carcinogenesis and model systems indicate that crosstalk occurs among them. We will use both conventional statistical approaches and a novel hierarchical model to comprehensively evaluate obesity and adult weight gain, candidate gene polymorphisms and haplotypes, and their potential joint and interactive effects on colon cancer. The unifying theme of this proposal is that obesity and candidate gene variants within these pathways may act alone or jointly to drive colon carcinogenesis. This study builds upon an ongoing population-based case-control study where epidemiologic data and DNA samples from 1,250 incident colon cancer cases and 1,500 population controls has already being collected. This relatively large study population will be readily available and allow us to dissect complex gene-gene and gene-obesity interactions to gain in- depth understanding of mechanistic link between obesity and colon carcinogenesis. This study builds upon an ongoing population-based case-control study where epidemiologic data and DNA samples from 1,250 incident colon cancer cases and 1,500 population controls have already being collected. This relatively large study population will be readily available and allow us to dissect complex gene-gene and gene-obesity interactions to gain in-depth understanding of mechanistic link between obesity and colon carcinogenesis
Keywords: 1-Phosphatidylinositol 3-Kinase; 5`-AMP-activated protein kinase; Address; Adult; Affect; Age; AKT1 gene; AKT2 gene; AKT3 gene; Biological; Biological Models; Body mass index; Body Weight Changes; BRAF gene; cancer risk; Candidate Disease Gene; Case-Control Studies; colon carcinogenesis; Colon Carcinoma; Complex; Data; Development; DNA; Epidemic; epidemiologic data; Epidemiologic Studies; Family; FOXO1A gene; FOXO3A gene; Gender; Genes; Genetic; Genetic Polymorphism; Goals; Growth Factor; Haplotypes; Health; Homeostasis; IGF1R gene; Insulin; Insulin Resistance; Insulin Signaling Pathway; insulin-related factor; IRS1 gene; IRS2 gene; Joints; Link; MAP2K1 gene; MAPK1 gene; MAPK3 gene; MDM2 gene; Measures; Mediating; men; Metabolic; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Modeling; mTOR protein; NF-kappa B; novel; Obesity; p65; Pathway Analysis; Pathway interactions; PDPK1 gene; Peroxisome Proliferator-Activated Receptors; PI3K/AKT; PIK3CA gene; PIK3CB gene; PIK3CG gene; PIK3R3 gene; Play; Population; population based; Population Control; Population Study; Proto-Oncogene Proteins c-akt; PTEN gene; PTPN11 gene; public health priorities; Raptors; Ras/Raf; Recruitment Activity; Research Priority; Risk; Role; Sampling; SHC1 gene; Signal Pathway; Signal Transduction; Somatomedins; STK11 gene; TNFRSF5 gene; TSC1 gene; TSC2 gene; Variant; Variation (Genetics); Weight Gain; Woman; Work
Relevance: This study builds upon an ongoing population-based case-control study where epidemiologic data and DNA samples from 1,250 incident colon cancer cases and 1,500 population controls have already being collected. This relatively large study population will be readily available and allow us to dissect complex gene-gene and gene-obesity interactions to gain in-depth understanding of mechanistic link between obesity and colon carcinogenesis
Project start date: 2009-09-01
Project end date: 2014-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-07-176
5R01CA136726-03 (2011): $472716
5R01CA136726-02 (2010): $505681
INSULIN RESISTANCE SYNDROME PATHWAY FACTORS AND COLON POLYPS
Li Li
Case Western Reserve University, 10900 Euclid Ave, Cleveland, Oh 44106-7015
Abstract: Increasing evidence from both model systems and epidemiologic studies support that insulin resistance resulting from long-term energy imbalance plays an important role in colon carcinogenesis. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace worldwide makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority. We hypothesize that candidate genes and associated biomarkers in the insulin-growth hormone-insulin-like growth factor (IGF)-insulin receptor substrate 1 (IRS-1) axis, adipogenesis pathway (adiponectin, and peroxisome proliferator-activated receptor-gamma), and dietary factors may work jointly to drive the development of insulin resistance syndrome, and subsequently, the development of colon adenomatous polyps, established precursors of colon cancer. We propose a screening colonoscopy-based incident case-control study to address the insulin resistance syndrome-colon polyp hypothesis by prospectively recruiting 750 incident colon polyp cases and 750 frequency-matched controls. We will determine the candidate gene variants and haplotypes, associated biomarkers, and insulin resistance syndrome related serum markers using blood samples, and collect dietary and lifestyle risk factor information using questionnaires. We will analyze the resulting information using novel statistical models to gain comprehensive understanding of the link between insulin resistance syndrome and colon polyps. Specifically, we will 1) to investigate the impact of insulin resistance syndrome as an integral entity on colon polyps; 2) to examine the impact of candidate genes and associated biomarkers in the insulin-GH-IGF-IRS axis and adipogenesis pathway on colon polyps; 3) to evaluate the association of dietary patterns, glycemic index and glycemic load with colon polyps; and 4) to synthesize the information on candidate genes, biomarkers, and diet by looking at their joint effects on colon polyps, and to comprehensively evaluate these factors´ potential direct as well as indirect (mediated by insulin resistance syndrome) impact on colon polyps. Our study will contribute to our understanding of how insulin resistance syndrome pathway-related candidate genes and dietary factors might work in concert in the etiology of colon adenomatous polyps. Our study may have profound implication for public health prevention/intervention strategies targeting at the early stages of the colon adenoma-cancer continuum
Keywords: ACRP30 protein; AFBP; Address; Adenoma of the Colon; Adenomatous Polyp of the Colon; Affect; Alpha-Pregnancy-Associated Endometrial Globulin; Amniotic Fluid Binding Protein; Articulation; Binding Protein-25; Binding Protein-26; Binding Protein-28; Biological; Biological Models; Blood Sample; Blood specimen; Cancers; Candidate Disease Gene; Candidate Gene; Case-Base Studies; Case-Comparison Studies; Case-Compeer Studies; Case-Control Studies; Case-Referent Studies; Case-Referrent Studies; Causality; Chemotherapy-Hormones/Steroids; Colon; Colon Cancer; Colon Carcinoma; Colon Neoplasms; Colonic Adenoma; Colonic Adenomatous Polyp; Colonic Carcinoma; Colonic Mass; Colonic Neoplasms; Colonic Polyps; Colonic Tumor; Colonoscopy; Data; Development; Diabetes Mellitus, Adult-Onset; Diabetes Mellitus, Ketosis-Resistant; Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus, Noninsulin Dependent; Diabetes Mellitus, Slow-Onset; Diabetes Mellitus, Stable; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Diet; Dietary Factors; Dietary Practices; Endocrine Gland Secretion; Epidemic; Epidemiologic Research; Epidemiologic Studies; Epidemiological Studies; Epidemiology Research; Equation; Etiology; Food; Frequencies (time pattern); Frequency; GHN; Gene variant; Genes; Genetic; Genetic Diversity; Genetic Polymorphism; Genetic Variation; Genotype; Glycemic Index; Glycemic Index Number; Goals; Growth Hormone; Growth Hormone 1; Growth Hormone Independent-Binding Protein; Haplotypes; Hormones; Human; Human, General; Humulin R; IBP-1; IGF; IGF-1; IGF-Binding Protein 1; IGF-I; IGF-I-SmC; IGF1; IGFBP-1; IGFBP1; IRS-1 protein; IRS1; Incidence; Individual; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin Receptor Substrate 1; Insulin Resistance; Insulin, Regular; Insulin-Like Growth Factor 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factors; Insulin-Like Growth-Factor Binding Protein 1; Insulin-Like Somatomedin Peptide I; Intermediary Metabolism; Intervention; Intervention Strategies; Joints; Life Style; Lifestyle; Link; METBL; MODY; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Markers, Serum; Maturity-Onset Diabetes Mellitus; Mediating; Metabolic; Metabolic Processes; Metabolism; Model System; Modeling; Models, Biologic; Models, Statistical; NIDDM; Non-Insulin Dependent Diabetes; Non-Insulin-Dependent Diabetes Mellitus; Novolin R; Nutrient; Obesity; PP12; PPAR; PPAR gamma; PPARG; PPARG1; PPARG2; PPARgamma; Pathway interactions; Peroxisome Proliferative Activated Receptor Gamma; Peroxisome Proliferator-Activated Receptor gamma; Peroxisome Proliferator-Activated Receptors; Pituitary Growth Hormone; Play; Polymorphism (Genetics); Polymorphism, Genetic; Predisposition; Preventive Intervention; Probabilistic Models; Process; Public Health; Questionnaires; Recruitment Activity; Research; Risk; Risk Factors; Role; STH; Screening procedure; Serum Markers; Societies; Somatomedin C; Somatomedins; Somatotropin; Staging; Statistical Methods; Statistical Models; Sulfation Factor; Susceptibility; Syndrome; T2D; T2DM; Therapeutic Hormone; Thiazolidinedione Receptor; Time; Tumor of the Colon; Type 2 diabetes; Type II diabetes; Variation (Genetics); Work; adipocyte complement-related protein 30-kDa; adipocyte, C1q and collagen domain containing protein; adipogenesis; adiponectin; adiposity; adult onset diabetes; allelic variant; apM-1 protein; apM1 (adipose-specific) protein; base; biomarker; colon carcinogenesis; colon polyp; corpulence; corpulency; corpulentia; disease causation; disease etiology; disease risk; disease/disorder etiology; disorder etiology; disorder risk; hGHN; insulin receptor substrate 1 protein; insulin resistant; insulinlike growth factor; interventional strategy; ketosis resistant diabetes; lipid biosynthesis; lipogenesis; malignancy; maturity onset diabetes; neoplasm/cancer; novel; obese; obese people; obese person; obese population; pathway; placental protein 12; polymorphism; preventional intervention strategy; public health medicine (field); recruit; screening; screenings; social role; somatotropic hormone
Budget start date: 1-SEP-2009
Budget end date: 31-AUG-2010
PFA/PA: RFA-CA-05-010
5U54CA116867-05_0002 (2009): $366161
Insulin Resistance Syndrome Pathway Factors & Colon Poly
Li Li
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5U54CA116867-030002 from National Cancer Institute IRG: ZCA1
Abstract: Increasing evidence from both model systems and epidemiologic studies support that insulin resistance resulting from long-term energy imbalance plays an important role in colon carcinogenesis. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace worldwide makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority. We hypothesize that candidate genes and associated biomarkers in the insulin-growth hormone-insulin-like growth factor (IGF)-insulin receptor substrate 1 (IRS-1) axis, adipogenesis pathway (adiponectin, and peroxisome proliferator-activated receptor-gamma), and dietary factors may work jointly to drive the development of insulin resistance syndrome, and subsequently, the development of colon adenomatous polyps, established precursors of colon cancer. We propose a screening colonoscopy-based incident case-control study to address the insulin resistance syndrome-colon polyp hypothesis by prospectively recruiting 750 incident colon polyp cases and 750 frequency-matched controls. We will determine the candidate gene variants and haplotypes, associated biomarkers, and insulin resistance syndrome related serum markers using blood samples, and collect dietary and lifestyle risk factor information using questionnaires. We will analyze the resulting information using novel statistical models to gain comprehensive understanding of the link between insulin resistance syndrome and colon polyps. Specifically, we will 1) to investigate the impact of insulin resistance syndrome as an integral entity on colon polyps; 2) to examine the impact of candidate genes and associated biomarkers in the insulin-GH-IGF-IRS axis and adipogenesis pathway on colon polyps; 3) to evaluate the association of dietary patterns, glycemic index and glycemic load with colon polyps; and 4) to synthesize the information on candidate genes, biomarkers, and diet by looking at their joint effects on colon polyps, and to comprehensively evaluate these factors potential direct as well as indirect (mediated by insulin resistance syndrome) impact on colon polyps. Our study will contribute to our understanding of how insulin resistance syndrome pathway-related candidate genes and dietary factors might work in concert in the etiology of colon adenomatous polyps. Our study may have profound implication for public health prevention/intervention strategies targeting at the early stages of the colon adenoma-cancer continuum.
Keywords: carcinogenesis, colon polyp, insulin sensitivity /resistance, neoplasm /cancer epidemiology, adenomatous polyp, adipocyte, biomarker, cell differentiation, gene environment interaction, glucose metabolism, hormone related neoplasm /cancer, insulin receptor, insulinlike growth factor, nutrition aspect of cancer, human subject, patient oriented research
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Stromal Cell Molecules Required For Lymphoma Generation
Li Li
Ochsner Clinic Foundation 1514 Jefferson Highway New Orleans, La 70121
Grant 3R01CA089057-05S1 from National Cancer Institute IRG: ET
Abstract: In the early stage, follicular lymphoma, one of the most common hematological malignancies in adults, is usually indolent, regressing spontaneously and showing susceptibility to chemotherapy. However, this tumor often recurs and can undergo blast transformation to an aggressive form, ultimately becoming a fatal disease. The generation and blast transformation of this tumor occur in close association with follicular dendritic cells (FDC) in the germinal center (GC). The objective is to identify the FDC signaling molecules by preparing the FDC-specific monoclonal antibodies that block FDC-mediated lymphoma cell proliferation in vitro and in vivo, and then use these antibodies to clone the genes of the signaling molecules from cDNA library of an FDC line, HK. The functions of the cloned genes will be investigated by expressing them in COS cells and evaluating them in in vitro and in vivo experimental models. A human lymphoma cell line of GC-origin, L3055, will be use, because growth of this cell line depends on FDC/HK in vitro and in vivo. Identification of the stromal cell molecules required for the growth of the lymphomageneses will lead to development of antagonists. Such antagonists may have a tremendous therapeutic potential to suppress the growth of malignant lymphomas or other tumors that metastasized to lymphoid follicles.
Keywords: biological signal transduction, dendritic cell, neoplasm /cancer immunology, nonHodgkin s lymphoma, complementary DNA, monoclonal antibody, neutralizing antibody, recombinant protein, transfection /expression vector, athymic mouse, molecular cloning
Project start date: 2001-07-01
Project end date: 2007-06-30
3R01CA089057-05S1 (2006): $123975
5R01CA089057-05 (2005): $233135
5R01CA089057-04 (2004): $233135
5R01CA089057-03 (2003): $233135
5R01CA089057-02 (2002): $166250
1R01CA089057-01A1 (2001): $166250
FAMILY-TO-FAMILY: PSYCHOEDUCATION TO IMPROVE CHILDREN´S OUTCOMES IN HIV+ FAMILIES
Li Li, Director
University Of California Los Angeles, Office Of Research Administration, Los Angeles, Ca 90095
Grant 5R01NR009922-05 from National Institute Of Nursing Research
Abstract: HIV has a negative intergenerational impact on families, particularly children with HIV+ parents (Rotheram-Borus et al., 1997). In order to improve the social, behavioral and mental health outcomes for children affected by HIV, we have designed the Family-to-Family (F2F) intervention that includes the critical, universal, program components identified by the NIMH Intervention Workgroup (in revision). All efficacious intervention programs frame the problem by providing information and shaping beliefs; enhance skills; establish supportive relationships; and remove environmental barriers to behavior change (e.g, HIV testing, ARV). We aim to evaluate a generic intervention approach that is culturally-tailored to families affected by HIV in a specific country, Thailand. The intervention builds on previous efficacious HIV family interventions, adapted to be sustainable in a developing country context. The F2F intervention for HIV+ parents and their family caregivers will assist families to cope with HIV-related stressors (disclosure, stigma, transmission, & custody), build skills for improving their own and their children´s adjustment, and establish supportive community relationships with other families affected by HIV. Families in Thailand need such an intervention 1 in 4 elderly adults in Thailand will raise an AIDS orphan, even with a relatively low national seroprevalence rate (1.2%). The study will proceed in 2 phases. In Phase 1, we will pilot and finalize the intervention, assessments, and procedures with 40 families, 10 of whom are "positive models." In Phase 2, families with HIV+ parents (400 HIV+ parents, 600 family caregivers) from 4 district hospitals in Chang Rai & Nakhon Ratchasima Provinces will be recruited to an intervention to benefit their 960 school-aged children aged 6-17 years. At their clinical care site, we will randomly assign families to either 1) F2F, a psychoeducational intervention for HIV+ parents and family caregivers delivered in drop-in groups by healthcare providers (not including their children); or 2) a Standard Care intervention. The impact of the F2F intervention will be monitored over 24 months (baseline, 3, 6, 12, 18, & 24 months). The primary outcomes are school-age children´s social, behavioral and mental health status. HIV+ parent´s and family caregivers´ health mental health, parenting skills, and family bonds are intermediate outcomes
Keywords: 0-11 years old; 21+ years old; AIDS; AIDS Virus; AIDS test; AIDS/HIV test; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immune Deficiency Syndrome Virus; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Acquired Immunodeficiency Syndrome Virus; Address; Adult; Adult Children; Adult Daughters; Adult Sons; Affect; Age; Aged 65 and Over; Area; Asians; Behavioral; Belief; Care Givers; Care giver Burden; Caregiver Burden; Caregivers; Cessation of life; Child; Child Mental Health; Child Support; Child Youth; Children (0-21); China; Collaborations; Communities; Country; Data; Death; Developed Countries; Developed Nations; Developing Countries; Developing Nations; Development; Disclosure; Disease; Disorder; District Hospitals; Drops; Drugs, Nonproprietary; Economic Income; Economical Income; Economics; Effectiveness; Elderly; Elderly, over 65; Face; Family; Family Care Giver; Family Caregiver; Funding; Gender; Generations; Generic Drugs; Group Meetings; HIV; HIV test; HTLV-III; Health; Health Care Providers; Health Personnel; Health Services; Health Status; Healthcare Providers; Healthcare worker; Hospitals, District; Household; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus test; Human, Adult; Human, Child; Immunologic Deficiency Syndrome, Acquired; Income; Industrialized Countries; Industrialized Nations; Information Disclosure; Intervention; Intervention Strategies; Intervention Trial; Investigators; LAV-HTLV-III; Less-Developed Countries; Less-Developed Nations; Level of Health; Life; Lymphadenopathy-Associated Virus; Mainland China; Measures; Medical; Meetings, Group; Mental Health; Mental Hygiene; Modeling; Models, Theoretic; Monitor; NIMH; National Institute of Mental Health; National Institute of Mental Health (U.S.); Offspring, Adult; Orphan; Outcome; PROV; Parenting; Parenting behavior; Parents; Participant; Persons; Phase; Procedures; Process; Programs (PT); Programs [Publication Type]; Province; Psychological Health; Randomized; Randomized Controlled Trials; Recruitment Activity; Red Cross; Republic of South Africa; Research; Research Personnel; Researchers; Role; Route; SUBGP; School-Age Population; Seroprevalences; Shapes; Site; Social support; South Africa; Stigmata; Stress; Subgroup; Support, Child; Symptoms; Thailand; Theoretical model; Third-World Countries; Third-World Nations; Time; Training; Transmission; Under-Developed Countries; Under-Developed Nations; Union of South Africa; United States National Institute of Mental Health; Virus-HIV; Work; adult human (21+); advanced age; aged; base; behavior change; behavioral health; care giver stress; caregiver stress; children; clinical care; coping; design; designing; disease/disorder; elders; encryption; experience; facial; generic; geriatric; grandchild; grandparent; health care personnel; health care service; health care worker; health provider; healthcare personnel; improved; intergenerational; intervention program; interventional strategy; late life; later life; medical personnel; meetings; older adult; older person; oriental; peer; primary outcome; programs; psychoeducation; psychoeducational intervention; quality assurance; randomisation; randomization; randomized controlled study; randomly assigned; recruit; school age; senior citizen; skills; social; social role; social stigma; social support network; standard care; stigma; stressor; transmission process; treatment provider; working group; youngster
Project start date: 2005-09-23
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
PFA/PA: RFA-MH-05-008
5R01NR009922-05 (2009): $571380
5R01NR009922-04 (2008): $580065
Family-to-Family: Psychoeducation To Improve Children s Outcomes In HIV+ Families
Li Li, Associate Research Sociologist
University Of California Los Angeles Office Of Research Administration Los Angeles, Ca 90095
Grant 5R01NR009922-03 from National Institute Of Nursing Research IRG: ZMH1
Abstract: HIV has a negative intergenerational impact on families, particularly children with HIV+ parents (Rotheram-Borus et al., 1997). In order to improve the social, behavioral and mental health outcomes for children affected by HIV, we have designed the Family-to-Family (F2F) intervention that includes the critical, universal, program components identified by the NIMH Intervention Workgroup (in revision). All efficacious intervention programs frame the problem by providing information and shaping beliefs; enhance skills; establish supportive relationships; and remove environmental barriers to behavior change (e.g, HIV testing, ARV). We aim to evaluate a generic intervention approach that is culturally-tailored to families affected by HIV in a specific country, Thailand. The intervention builds on previous efficacious HIV family interventions, adapted to be sustainable in a developing country context. The F2F intervention for HIV+ parents and their family caregivers will assist families to cope with HIV-related stressors (disclosure, stigma, transmission, and custody), build skills for improving their own and their children s adjustment, and establish supportive community relationships with other families affected by HIV. Families in Thailand need such an intervention 1 in 4 elderly adults in Thailand will raise an AIDS orphan, even with a relatively low national seroprevalence rate (1.2%). The study will proceed in 2 phases. In Phase 1, we will pilot and finalize the intervention, assessments, and procedures with 40 families, 10 of whom are "positive models." In Phase 2, families with HIV+ parents (400 HIV+ parents, 600 family caregivers) from 4 district hospitals in Chang Rai and Nakhon Ratchasima Provinces will be recruited to an intervention to benefit their 960 school-aged children aged 6-17 years. At their clinical care site, we will randomly assign families to either 1) F2F, a psychoeducational intervention for HIV+ parents and family caregivers delivered in drop-in groups by healthcare providers (not including their children); or 2) a Standard Care intervention. The impact of the F2F intervention will be monitored over 24 months (baseline, 3, 6, 12, 18, and 24 months). The primary outcomes are school-age children s social, behavioral and mental health status. HIV+ parent s and family caregivers health mental health, parenting skills, and family bonds are intermediate outcomes.
Keywords: AIDS education /prevention, HIV infection, children, education evaluation /planning, family structure /dynamics, southeast Asia, belief, coping, culture, psychological stressor, social adjustment, social support network, behavioral /social science research tag, clinical research, human subject
Project start date: 2005-09-23
Project end date: 2010-06-30
5R01NR009922-03 (2007): $579263
HIV Related Stigma Among Service Providers In China
Li Li, Associate Research Sociologist
University Of California Los Angeles Office Of Research Administration Los Angeles, Ca 90095
Grant 5R01MH070931-03 from National Institute Of Mental Health IRG: ZRG1
Abstract: China has 1 million Persons Living with HIV (PLH) with the rate rising exponentially over the last five years. Yunnan Province represents the largest portion of China s HIV epidemic, primarily among injecting drug users. While undocumented systematically, substantial experience with other stigmatizing disorders and anecdotal accounts document that HIV-related stigma is high and impedes effective responses for prevention and care in China. This application addresses HIV-related stigma among health care providers in Yunnan Province. Stigma is defined as a multidimensional construct with sociocultural, structural, and interpersonal determinants; providers stigmatizing attitudes and behaviors can be influenced by educating providers about HIV-related policies and providing access to implement the policies, training providers over time to be knowledgeable about transmission and how to protect themselves, acceptance of PLH, and diffusing positive messages to peers. It is anticipated that providers attitudes and behaviors will influence health care delivery to PLH. A collaborative research team from the Chinese Center for Disease Control and the UCLA Center for Community Health will implement a 3-year investigation among health providers and administrators in Yunnan Province in 3 phases. Phase 1 will consist of qualitative interviews regarding HW-related experiences, stigma, barriers and facilitators of care to PLH, and assessment measures for these concepts with 1) 20 PLH and 10 of their family members; 2) 20 service providers; and 3) 20 health service administrators, with the addition of questions focused on HIV-related policies and procedures. Phase 2 will consist of a survey of 900 service providers and administrators in Yunnan Province on the prevalence and sources of HIV-related stigma. Using the results from the initial phases, an intervention will be developed and pilot tested with 50 service providers and evaluated using a comparison group of 50 providers over 6-months. The goals of the intervention will be to reduce stigmatizing attitudes towards PLH and diffusion of positive messages about PLH from service providers, education on HIV-related policies and access to resources to implement HW testing, universal precautions, and HIV treatment and care (using current Chinese standards of care). These data will prepare the team to conduct a randomized controlled trial across different levels of health care providers in China.
Keywords: AIDS, China, attitude, health administration, health care personnel, health care quality, human immunodeficiency virus, psychosocial separation, AIDS /HIV test, AIDS education /prevention, culture, education evaluation /planning, experience, family structure /dynamics, health care policy, health care service availability, behavioral /social science research tag, clinical research, health services research tag, health survey, human subject, interview
Project start date: 2003-09-12
Project end date: 2007-06-30
5R01MH070931-03 (2005): $247250
Sponsored Links Excellgen http://Excellgen.com
5R01MH070931-02 (2004): $247250
1R01MH070931-01 (2003): $260375
GENETIC CONTROL OF SMOOTH MUSCLE GENE EXPRESSION
Li Li
Internal Medicinewayne State University
sponsored Program Administration
detroit, Mi 48202
Grant 5R01HL058916-04 from National Heart, Lung, And Blood Institute IRG: ECS
Abstract: Adapted ) Abnormal proliferation and phenotypic change of smooth muscle cells (SMC) have been associated with pathogenesis of congenital and acquired human vascular disease. However, little is understood about the molecular mechanisms that control SMC lineage determination, proliferation and differentiation during cardiovascular development. To address these questions, the investigators chose to characterize the regulation of SM22, a gene known to be a marker for adult smooth muscle, in the mouse. During embryogenesis, this gene is first expressed in all three muscle lineages, and then becomes restricted to all different types of SMCs. Surprisingly, the SM22 promoter is active only in a subset of arterial SMCs, not visceral, nor coronary, nor vena cava SMCs. Site directed mutagenesis of the SM22 promoter reveals that the proximal CArG box is required for its temporospatial expression in transgenic mice, suggesting that SRF (serum Responsive Factor), the CArG box binding protein, may play an important role in SM22 gene regulation. The overall goal of this proposal is to define the molecular mechanisms that discern the differential expression of the SM22 promoter in different subtypes of SMCs. The project will have two major aims, 1) to define the critical sequences in the proximal CArG box that required for specific activation of the promoter in arterial SMCs. 2) to define the cis-acting elements that confer specific expression of SM22 in SMC subtypes such as visceral and vena cava SMCs. These studies represent an important aspect of current vascular research in understanding the molecular mechanisms that control SMC proliferation, differentiation and lineage determination during cardiovascular development. Elucidation of the molecular mechanisms governing SMC differentiation and determination will open up a new frontier to develop molecular gene therapies for both congenital and acquired cardiovascular diseases
Keywords: angiogenesis, cell differentiation, developmental genetics, genetic regulatory element, mammalian embryology, vascular smooth muscle binding protein, cell proliferation, genetic promoter element laboratory mouse, site directed mutagenesis, transgenic animal
Project start date: 1998-09-11
Project end date: 2003-08-31
5R01HL058916-04 (2001): $283211
5R01HL058916-03 (2000): $275715
5R01HL058916-02 (1999): $268434
1R01HL058916-01A1 (1998): $274750
Li Li
Case Western Reserve University
Project start date: 2011-01-01
Project end date: 2012-12-31
Sponsored Links Excellgen http://Excellgen.com