Current Funded Research
Agency: NIH National Institute of Allergy and Infectious Diseases Project Number 1R01AI138921-01A1
Finding a new HIV cure therapy is a major focus of NIH HIV research program. Our Sendai virus vector can genetically modify hematopoietic stem cells to confer HIV-resistance at unprecedented efficiencies. This overcomes the major obstacles in the field for anti HIV stem cell based gene therapy, and allows for the possibility of a HIV cure – the successful long-term drug-free control of HIV disease.
The objective of this research is to understand the role of genetic factors on the pathway connecting insulin resistance (IR) and breast cancer risk among postmenopausal women, a population highly susceptible to breast cancer, and further determine how modifiable factors such as obesity and obesity-related lifestyle factors play a role in this association. Results from this study can improve understanding of the molecular pathways connecting IR-related genetic markers and breast cancer risk, and may yield valuable new insight into the study of gene–lifestyle interactions. The results can also lead to development of behavioral and pharmacotherapeutic (e.g., potential gene-targeting agents or demethylating agents) interventions for those with risk genotypes, in order to reduce IR and modify the insulin molecular pathway, thus reducing breast cancer risk and poor prognosis in postmenopausal women.
Agency: NIH National Institute of Allergy and Infectious Diseases Project Number: 1R01AI100652-01A1
Hematopoietic stem/progenitor cell (HSPC) based gene therapy holds great promise to provide long-term control of HIV with a single treatment. Like HAART, it is essential to combine multiple drugs to effectively suppress HIV and prevent drug resistant HIV escape mutants. The overall hypothesis of this proposal is that stable introduction of highly potent combinations of anti-HIV genes capable of inhibiting multiple early and late steps of HIV viral lifecycle into HSPC will provide lifelong protection from HIV infection The safety and efficacy of anti-HIV HSPC gene therapy strategies, including inhibition of HIV, lowering of viral load and selective growth advantage of protected cells and prevention of resistance will be evaluated in the recently developed human bone marrow, liver and thymus (BLT) transplanted mouse model. Specific aims are 1) To develop novel multi-pronged anti-HIV gene therapeutic lentiviral vectors and characterize therapeutic reagents to inhibit HIV infection in HSPC and their progeny in vitro 2) To determine the long-term anti-gene expression and stable control of HIV through genetically engineered human HSPC transplant in the BLT mouse model. The approach is innovative because it focuses on novel HIV-1 target HSPC protection and the development of novel potent, broad-range early stage and late stage anti-HIV combinations, maximizing the potential to HIV replication not only in HSPC but also all potential target cells. The proposed research is significant because the results may ultimately lead to an innovative, more effective, more convenient, less toxic, safe and more cost effective way of controlling HIV infection than is currently available. The long-term goal is to advance HSPC based gene therapy research and make rapid progress towards providing a new therapy that leads to stable control of HIV by a single treatment. PUBLIC HEALTH RELEVANCE: Our proposed research will positively impact public health with the development of an anti-HIV gene therapy by blocking the multiple early and late stages of the HIV infection. Ultimately, HIV infection will be controlled with a single treatment by protecting the hematopoietic stem cells and their progeny. This research will provide significant knowledge towards the long-term goal of the NIH "HIV cure."
Agency: NIH, National Institute of Nursing Research Project Number: 1R01NR017190-01A1
Over 26 million persons have Type 2 diabetes (T2DM), and poorly managed T2DM contributes to early morbidity and mortality; therefore, improving T2DM Fhealth outcomes and preventing T2DM-related complications through excellent self-care is a public health priority. Effective T2DM self-care requires intact cognition and mood, which are linked to brain structural changes. We will examine brain structural status between T2DM patients and non-diabetic healthy subjects, as well as gender differences, and investigate relationships between brain changes and self-care, mood, cognition, and impact of A1C levels in T2DM subjects, which could impact clinical practice and self-care of T2DM patients through the identification and testing of novel therapeutic interventions to protect or restore the brain, minimize or prevent cognitive and mood dysfunction, and thus, improve T2DM self-care and health outcomes in this high-risk patient population.
Funding Agency: National Institutes of Health National Heart, Lung and Blood Institute Project Number: 1R21HL145002-01
Narrative Hookah (water-pipe) smoking has quickly grown to become a major global tobacco epidemic among youth; with electronic hookahs more recently increasing in popularity especially among young female adults, who endorse marketing claims that these products are a safer alternative to traditional hookah, but scientific evidence is lacking. Our study aims to elucidate the comparative effects of traditional hookah smoking vs. electronic hookah inhalation on human vascular and endothelial function; and examine the role of inflammation and oxidative stress as likely mechanisms in hookah-related cardiovascular disease pathogenesis. Findings will: 1) provide rigorous scientific evidence to clarify the vascular effects, and the potential mechanisms, of traditional versus e-hookah exposure on known cardiac risk factors; and 2) provide a scientific basis needed to inform FDA tobacco regulatory science for the development of hookah policy regulation.
Funding Agency: NIH National Institute on Aging Project Number: 5K23AG055668-02
Poor sleep in both Alzheimer's disease (AD) patients and their caregivers is associated with adverse health outcomes, and increases risk of institutionalization in individuals with AD. This proposal will pilot test an innovative sleep intervention targeting both groups simultaneously. Improved sleep in AD patients and their caregivers may improve health and quality of life, and may prevent or delay admission of AD patients to institutional settings, potentially leading to decreased healthcare costs.